[Birth and metamorphosis of Landouzy-Dejerine progressive atrophic myopathy].

On June 20th, 1880, was admitted at the "Hôpital de la Charité" in Paris, a 21 years-old man showing a very severe atrophy of most of his muscles. This case was going to mark the history of the neuromuscular diseases. In the present article are presented the main clinical, genetic, electrophysiological and anatomical data of this patient. It was tried to reconstitute how they were presented to Landouzy and Dejerine, who found in these data some of the features previously reported by Duchenne, de Boulogne, in 1852 as "atrophie musculaire progressive", and considered after the first post-mortem examination by Cruveilhier (1853) as being of neurogenic origin. In opposition with this theory, Landouzy and Dejerine proposed to refer to their case as "myopathie atrophique progressive", emphasizing thus the concept of "myopathy without neuropathy". The criteria proposed for the recognition of the new entity were perfectly described in their two memoirs (1885 and 1886). The characters of facial involvement, the occasional early onset, the selective and often asymmetrical weakness and atrophy of the limb muscles, the variability in severity from one member to another in the same family, were clearly showed. Furthermore, two cases reported in the 1886 memoir presented some involvement of the facial muscles which was demonstrated only by histological examination. The present article evokes the polemical discussion about the relationship of the "myopathie atrophique progressive" with the juvenile form of muscle dystrophy described by Erb at the same time, but without any anatomical or histological data. It is indicated also how the different views about the "scapulo-humeral" forms led to some metamorphosis of the "myopathie atrophique progressive" in "facio-scapulo-humeral dystrophy" in further classifications. This article is illustrated with micrographs taken from the original sections of Dejerine, which could be traced up to now and probably are reproduced photographically here for the first time.

On June 20th, 1880, was admitted at the "Hôpital de la Charité" in Paris, a

    21 years-old
    AGE

    man
    GENDER

 showing a

    very severe atrophy of most of his muscles
    SYMPTOMS

. This case was going to mark the history of the

    neuromuscular diseases
    DIAGNOSIS

. In the present article are presented the main clinical, genetic, electrophysiological and anatomical data of this patient. It was tried to reconstitute how they were presented to Landouzy and Dejerine, who found in these data some of the features previously reported by

    Duchenne
    DIAGNOSIS

, de Boulogne, in 1852 as "

    atrophie musculaire progressive"
    DIAGNOSIS

, and considered after the first

    post-mortem
    PARACLINICAL

 examination by Cruveilhier (1853) as being of

    neurogenic origin
    DIAGNOSIS

. In opposition with this theory, Landouzy and Dejerine proposed to refer to their case as "

    myopathie atrophique progressive"
    DIAGNOSIS

, emphasizing thus the concept of "

    myopathy without neuropathy
    DIAGNOSIS

    "
    DIAGNOSIS

. The criteria proposed for the recognition of the new entity were perfectly described in their two memoirs (1885 and 1886). The characters of

    facial involvement
    SYMPTOMS

, the

    occasional early onset
    SYMPTOMS

, the

    selective and often asymmetrical weakness and atrophy of the limb muscles
    SYMPTOMS

, the variability in severity from one member to another in the same family, were clearly showed. Furthermore, two cases reported in the 1886 memoir presented

    some involvement of the facial muscles
    SYMPTOMS

 which was demonstrated only by

    histological examination
    PARACLINICAL

. The present article evokes the polemical discussion about the relationship of the "

    myopathie atrophique progressive"
    DIAGNOSIS

 with the

    juvenile form of muscle dystrophy
    DIAGNOSIS

 described by Erb at the same time, but

    without any anatomical or histological data
    NEG_FINDINGS

. It is indicated also how the different views about the "

    scapulo-humeral" forms
    DIAGNOSIS

 led to some metamorphosis of the "

    myopathie atrophique progressive" in "facio-scapulo-humeral dystrophy"
    DIAGNOSIS

 in further classifications. This article is illustrated with micrographs taken from the original sections of Dejerine, which could be traced up to now and probably are reproduced photographically here for the first time.


Translocation (X;6) in a female with Duchenne muscular dystrophy: implications for the localisation of the DMD locus.

A female with Duchenne muscular dystrophy who was a carrier of a balanced translocation t(X;6)(p21;q21) is reported. Four other previously described (X;A) translocations associated with DMD share with the present case a breakpoint at Xp21. The extremely low probability of five independent (X;A) translocations having a breakpoint at Xp21 points to a non-rand association of this site with the DMD phenotype. A DMD locus at Xp21 could be damaged by the translocation, giving rise to Duchenne muscular dystrophy. Alternatively, a pre-existing DMD gene could weaken the chromosome, favouring breaks at Xp21.

A

    female
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who was a carrier of a

    balanced translocation t(X;6)(p21;q21)
    GENETICS

 is reported. Four other previously described

    (X;A) translocations
    GENETICS

 associated with

    DMD
    DIAGNOSIS

 share with the present case a

    breakpoint at Xp21
    GENETICS

. The extremely low probability of five

    independent (X;A) translocations having a breakpoint at Xp21
    GENETICS

 points to a non-rand association of this site with the

    DMD phenotype
    GENETICS

. A

    DMD locus at Xp21
    GENETICS

 could be damaged by the translocation, giving rise to

    Duchenne muscular dystrophy
    DIAGNOSIS

. Alternatively, a

    pre-existing DMD gene could weaken the chromosome
    GENETICS

, favouring

    breaks at Xp21
    GENETICS

.

Duchenne muscular dystrophy
DMD
Duchenne muscular dystrophy


Myocardial infarction in a child aged ten with Duchenne muscular dystrophy.

The authors describe the clinical picture, ECG, vectorcardiographic, and serum enzyme assays in one case of acute myocardial infarction occurring after a severe physical exertion in a child aged 10 with progressive muscular dystrophy of the Duchenne type. The picture differs considerably from the electrical aspects of "pseudonecrosis" that interstitial fibrosis of some portions of the left ventricle may produce in this myopathy.

The authors describe the clinical picture,

    ECG
    PARACLINICAL

,

    vectorcardiographic
    PARACLINICAL

, and

    serum enzyme assays
    PARACLINICAL

 in one case of

    acute myocardial infarction
    SYMPTOMS

 occurring after a

    severe physical exertion
    SYMPTOMS

 in a

    child
    AGE

    aged 10
    AGE

 with

    progressive muscular dystrophy of the Duchenne type
    DIAGNOSIS

. The picture differs considerably from the

    electrical aspects of "pseudonecrosis"
    SYMPTOMS

 that

    interstitial fibrosis of some portions of the left ventricle
    MICROSCOPIC

 may produce in this

    myopathy
    DIAGNOSIS

.

acute myocardial infarction
severe physical exertion
electrical aspects of "pseudonecrosis"


Clinically manifesting carriers in Duchenne muscular dystrophy.

Three manifesting carriers of Duchenne muscular dystrophy were examined clinically and histologically. All had muscle weakness in the upper and lower limbs without facial muscle involvement, onset being at the ages of 35, 19 and 25 years, respectively. Pseudohypertrophy of calves was evident in all cases. Biochemical, electrocardiographic and histological observations revealed the presence of myopathy in all cases. Sex chromatin patterns were normal. Compared with the manifesting carriers previously reported by others, at least one case showed more severe histological findings which were typical of the advanced stage of Duchenne muscular dystrophy. The cardiac involvement in three cases was moderate. A possible involvement of other factors besides Lyonization influencing the development of myopathy in the carriers is suggested.

Three manifesting carriers of

    Duchenne muscular dystrophy
    DIAGNOSIS

 were examined clinically and histologically. All had

    muscle weakness in the upper and lower limbs
    SYMPTOMS

    without facial muscle involvement
    NEG_FINDINGS

, onset being

    at the ages of 35, 19 and 25 years
    AGE

, respectively.

    Pseudohypertrophy of calves
    SYMPTOMS

 was evident in all cases.

    Biochemical, electrocardiographic and histological observations
    PARACLINICAL

 revealed the presence of

    myopathy
    DIAGNOSIS

 in all cases.

    Sex chromatin patterns were normal
    NEG_FINDINGS

. Compared with the manifesting carriers previously reported by others, at least one case showed

    more severe histological findings
    SYMPTOMS

 which were typical of the

    advanced stage of Duchenne muscular dystrophy
    DIAGNOSIS

. The

    cardiac involvement
    SYMPTOMS

 in three cases

    was moderate
    SYMPTOMS

. A possible involvement of other factors besides Lyonization influencing the development of

    myopathy
    DIAGNOSIS

 in the carriers is suggested.

without facial muscle involvement
Sex chromatin patterns were normal


Duchenne muscular dystrophy (DMD) in a female with an X/autosome translocation: further evidence that the DMD locus is at Xp21.

An isolated case of Duchenne muscular dystrophy in a female who has a de novo t(X;5)(p21;q35) translocation is described. The similarities between this patient and four previously reported females with Duchenne muscular dystrophy are discussed. It is concluded that the locus for Duchenne muscular dystrophy is at Xp21 and, furthermore, that this site may be particularly susceptible both to chromosome breakage and exchange and to gene mutation.

An isolated case of

    Duchenne muscular dystrophy
    DIAGNOSIS

 in a

    female
    GENDER

 who has a

    de novo t(X;5)(p21;q35) translocation
    GENETICS

 is described. The similarities between this patient and four previously reported

    females
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 are discussed. It is concluded that the

    locus for Duchenne muscular dystrophy
    GENETICS

    is at Xp21
    GENETICS

 and, furthermore, that this site may be particularly susceptible both to

    chromosome breakage and exchange
    GENETICS

 and to

    gene mutation
    GENETICS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy

de novo t(X;5)(p21;q35) translocation
locus for Duchenne muscular dystrophy
is at Xp21
chromosome breakage and exchange
gene mutation


Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation.

Three cases from 2 families had muscle weakness with predilection for distal extremities, predominantly affecting the tibialis anterior muscles, and onset in early adulthood. The disorder seemed to be inherited through an autosomal recessive trait. The EMG demonstrated a myopathic pattern and CPK was mildly elevated. The striking finding in their muscle biopsies was the presence of "rimmed" vacuoles which had acid phosphatase-positive autophagic activity and which contained numerous concentric lamellar bodies in various forms (myeloid and cabbage bodies). Despite rapid clinical progression, not only necrotic fibers with phagocytosis, as seen in Duchenne dystrophy, but also evidence of regeneration were virtually absent. Continuous destruction of myofibrils by activation of certain lysosomal proteolytic enzymes might be responsible for the production of atrophic fibers.

Three cases from 2 families had

    muscle weakness with predilection for distal extremities
    SYMPTOMS

,

    predominantly affecting the tibialis anterior muscles
    SYMPTOMS

, and onset in

    early adulthood
    AGE

. The disorder seemed to be

    inherited through an autosomal recessive trait
    GENETICS

. The

    EMG
    PARACLINICAL

 demonstrated a

    myopathic pattern
    SYMPTOMS

 and

    CPK was mildly elevated
    BIOCHEMICAL

. The striking finding in their

    muscle biopsies
    PARACLINICAL

 was the

    presence of "rimmed" vacuoles which had acid phosphatase-positive autophagic activity and which contained numerous concentric lamellar bodies in various forms (myeloid and cabbage bodies)
    MICROSCOPIC

. Despite

    rapid clinical progression
    SYMPTOMS

, not only

    necrotic fibers with phagocytosis
    MICROSCOPIC

, as seen in

    Duchenne dystrophy
    DIAGNOSIS

, but also

    evidence of regeneration were virtually absent
    NEG_FINDINGS

.

    Continuous destruction of myofibrils
    MICROSCOPIC

 by

    activation of certain lysosomal proteolytic enzymes
    BIOCHEMICAL

 might be responsible for the

    production of atrophic fibers
    MICROSCOPIC

.


Manifesting carrier of x-linked Duchenne muscular dystrophy.

The authors have investigated the uncommon occurrence of a boy affected with Duchenne muscular dystrophy (DMD) whose mother showed myopathic features in the clinical history, EMG, biochemical tests and muscle biopsy. This study suggests that the patient's mother is a manifesting carrier of X-linked DMD with clinical, neurophysiological, biochemical and histological findings of X-linked DMD with an almost complete inactivation of the paternal X-chromosome (lyonization).

The authors have investigated the uncommon occurrence of a

    boy
    GENDER

 affected with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 whose

    mother showed myopathic features
    FAMILY

 in the

    clinical history
    PARACLINICAL

,

    EMG
    PARACLINICAL

,

    biochemical tests
    PARACLINICAL

 and

    muscle biopsy
    PARACLINICAL

. This study suggests that the patient's

    mother is a manifesting carrier of X-linked DMD
    FAMILY

 with

    clinical, neurophysiological, biochemical and histological findings of X-linked DMD
    SYMPTOMS

    with an almost complete inactivation of the paternal X-chromosome (lyonization)
    GENETICS

.


Proximal muscle weakness in children.

In as many as half of the children referred to a muscle disease clinic, the original diagnosis is ultimately changed. Five cases histories are reviewed here in which Duchenne muscular dystrophy had been mistakenly diagnosed 3 to 12 years previously and the correct diagnosis was made only after repeat muscle biopsy or biopsy review. Four boys had diseases with a much better prognosis, and one boy did not have a muscle disease at all.

In as many as half of the

    children
    AGE

 referred to a

    muscle disease
    DIAGNOSIS

 clinic, the original diagnosis is ultimately changed. Five cases histories are reviewed here in which

    Duchenne muscular dystrophy
    DIAGNOSIS

 had been

    mistakenly diagnosed
    NEG_FINDINGS

 3 to 12 years previously and the correct diagnosis was made only after

    repeat muscle biopsy
    PARACLINICAL

 or

    biopsy review
    PARACLINICAL

. Four

    boys
    GENDER

 had diseases with a much better prognosis, and one

    boy
    GENDER

    did not have a muscle disease at all
    NEG_FINDINGS

.

muscle disease
Duchenne muscular dystrophy

mistakenly diagnosed
did not have a muscle disease at all


Sporadic Duchenne muscular dystrophy in females; genetic counseling of women with pelvifemoral muscular dystrophy.

The first two cases of sporadic Duchenne muscular dystrophy (DMD) in females without a family history of DMD are reported. Both females had normal chromosomes and were identified as DMD by in vitro studies of protein synthesis by muscle ribosomes and by carrier studies of the mother of the proband. These observations are important for the genetic counselor. The possible diagnosis X-linked DMD has to be considered for every female with sporadic pelvifemoral MD, and carrier studies have to be requested for the proband's mother and possibly other maternal female relatives.

The first two cases of

    sporadic Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 in

    females
    GENDER

    without a family history of DMD
    NEG_FINDINGS

 are reported. Both

    females
    GENDER

 had

    normal chromosomes
    NEG_FINDINGS

 and were identified as

    DMD
    DIAGNOSIS

 by

    in vitro studies of protein synthesis by muscle ribosomes
    PARACLINICAL

 and by

    carrier studies of the mother of the proband
    PARACLINICAL

. These observations are important for the

    genetic counselor
    PARACLINICAL

. The possible diagnosis

    X-linked DMD
    GENETICS

 has to be considered for every

    female
    GENDER

 with

    sporadic pelvifemoral MD
    FAMILY

, and

    carrier studies
    PARACLINICAL

 have to be requested for the proband's mother and possibly other

    maternal female relatives
    PARACLINICAL

.

without a family history of DMD
normal chromosomes


Dynamic gait electromyography study in Duchenne muscular dystrophy (DMD) patients.

Preoperative and postoperative dynamic gait electromyography (EMG) weas performed on 15 patients 8 to 13 year of age with Duchenne's muscular dystrophy who underwent Achilles tendon lengthening and posterior tibial tendon transfer anteriorly through the interosseous ligament for correction of equinus and equinovarus foot deformities. The muscles tested preoperatively (anterior tibial, soleus, gastrocnemius, posterior tibial, peroneal longus, and peroneal brevis) showed phase changes. It is believed that patients with weakened leg muscles fire multiple muscle groups out of phase in an attempt to overcome the action of the stronger muscles, thus stabilizing the limb for ambulation. Postoperative EMGs, performed with the patients walking in long leg braces after the deformity had been corrected, showed little activity in the muscles tested. As the patients became dependent on the brace, the need for the muscles to be active out of phase was eliminated. The transferred posterior tibial muscle appeared to be active both clinically and electromyographically.

    Preoperative and postoperative dynamic gait electromyography (EMG)
    PARACLINICAL

 weas performed on 15 patients

    8 to 13 year of age
    AGE

 with

    Duchenne's muscular dystrophy
    DIAGNOSIS

 who underwent

    Achilles tendon lengthening and posterior tibial tendon transfer anteriorly through the interosseous ligament
    MEDICATION

 for correction of

    equinus and equinovarus foot deformities
    SYMPTOMS

. The

    muscles tested preoperatively (anterior tibial, soleus, gastrocnemius, posterior tibial, peroneal longus, and peroneal brevis) showed phase changes
    SYMPTOMS

. It is believed that patients with

    weakened leg muscles fire multiple muscle groups out of phase
    SYMPTOMS

 in an attempt to

    overcome the action of the stronger muscles
    NEG_FINDINGS

, thus

    stabilizing the limb for ambulation
    MEDICATION

.

    Postoperative EMGs
    PARACLINICAL

, performed with the patients

    walking in long leg braces
    MEDICATION

 after the

    deformity had been corrected
    MEDICATION

, showed

    little activity in the muscles tested
    NEG_FINDINGS

. As the patients became

    dependent on the brace
    MEDICATION

, the

    need for the muscles to be active out of phase
    NEG_FINDINGS

 was eliminated. The

    transferred posterior tibial muscle appeared to be active
    SYMPTOMS

 both clinically and electromyographically.


Living with progressive childhood illness: parental management of neuromuscular disease.

This investigation is an exploratory study of parental management of progressive childhood neuromuscular disease. It focuses on parents for their significance as the primary managers of their children's diseases. The study, through its fieldwork component for the collection of data, utilizes participant observation. The researcher lived with each of six families for four days and nights to learn of the main concerns of parents with children who have Duchenne muscular dystrophy and Werdnig-Hoffmann disease, and the ways in which the parents manage these concerns. General patterns of positive parental management are defined and are followed by descriptions, in functional terms, of some of the strategies that parents employ to carry out these patterns.

This investigation is an exploratory study of parental management of

    progressive childhood neuromuscular disease
    DIAGNOSIS

. It focuses on

    parents
    GENDER

 for their significance as the primary managers of their children's diseases. The study, through its fieldwork component for the collection of data, utilizes

    participant observation
    PARACLINICAL

. The researcher lived with each of six families for four days and nights to learn of the main concerns of parents with

    children
    AGE

 who have

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    Werdnig-Hoffmann disease
    DIAGNOSIS

, and the ways in which the parents manage these concerns. General patterns of positive parental management are defined and are followed by descriptions, in functional terms, of some of the strategies that parents employ to carry out these patterns.


Atrioventricular block and supraventricular arrhythmias with X-linked muscular dystrophy.

This report describes a family showing muscular dystrophy and atrioventricular block with an x-linked hereditary transmission. Among a known pedigree of 101 family members, 12 males were found to have skeletal muscle involvement and six needed pacemakers around age 30 years. Unlike the x-linked muscular dystrophies of Duchenne and of Becker, the predominant skeletal involvement was in humeral muscles, was usually very mild, and did not produce incapacitation. Cardiac involvement consisted of various atrial arrhythmias and atrioventricular block. The few sporadic reports of other families that describe the same disease under different names are briefly reviewed. Recognition of this subtle muscular dystrophy is important for early detection of incipient complete atrioventricular block to prevent fatal complications by pacemaker insertion.

This report describes a family showing

    muscular dystrophy
    DIAGNOSIS

 and

    atrioventricular block
    SYMPTOMS

 with an

    x-linked hereditary transmission
    GENETICS

. Among a known pedigree of 101 family members, 12

    males
    GENDER

 were found to have

    skeletal muscle involvement
    SYMPTOMS

 and six needed

    pacemakers
    MEDICATION

 around

    age 30 years
    AGE

. Unlike the

    x-linked
    GENETICS

    muscular dystrophies
    DIAGNOSIS

 of

    Duchenne
    DIAGNOSIS

 and of

    Becker
    DIAGNOSIS

, the

    predominant skeletal involvement was in humeral muscles
    SYMPTOMS

, was usually

    very mild
    SYMPTOMS

, and

    did not produce incapacitation
    NEG_FINDINGS

.

    Cardiac involvement
    SYMPTOMS

 consisted of

    various atrial arrhythmias
    SYMPTOMS

 and

    atrioventricular block
    SYMPTOMS

. The few sporadic reports of other families that describe the same disease under different names are briefly reviewed. Recognition of this

    subtle muscular dystrophy
    DIAGNOSIS

 is important for early detection of

    incipient complete atrioventricular block
    SYMPTOMS

 to prevent

    fatal complications
    SYMPTOMS

 by

    pacemaker insertion
    MEDICATION

.

muscular dystrophy
muscular dystrophies
Duchenne
Becker
subtle muscular dystrophy

x-linked hereditary transmission
x-linked


Muscular dystrophy in six young girls.

Clinical and genetic studies were made on progressive muscular dystrophy in six young girls. No chromosome abnormality was observed in these patients. The pedigree of one case implied a sex-linked recessive trait, and clinical features were identical with Duchenne dystrophy. The clinical manifestations of two sisters in another family were less severe than in their brother with Duchenne dystrophy. The clinical differences among these three cases are well explained by the Lyon hypothesis. Three other cases were compatible with childhood muscular dystrophy of autosomal recessive inheritance.

    Clinical and genetic studies
    PARACLINICAL

 were made on

    progressive muscular dystrophy
    DIAGNOSIS

 in six

    young
    AGE

    girls
    GENDER

.

    No chromosome abnormality was observed
    NEG_FINDINGS

 in these patients. The

    pedigree
    FAMILY

 of one case

    implied a sex-linked recessive trait
    GENETICS

, and

    clinical features were identical with Duchenne dystrophy
    SYMPTOMS

.

    The clinical manifestations of two sisters in another family were less severe than in their brother with Duchenne dystrophy
    FAMILY

. The clinical differences among these three cases are well explained by the Lyon hypothesis. Three other cases were compatible with

    childhood muscular dystrophy
    DIAGNOSIS

 of

    autosomal recessive inheritance
    GENETICS

.

progressive muscular dystrophy
childhood muscular dystrophy

implied a sex-linked recessive trait
autosomal recessive inheritance


Duchenne type muscular dystrophy and consanguinity: difficulties in pedigree analysis.

We report the case of a 2-year-old girl who had signs of Duchenne type muscular dystrophy on clinical, electromyographic, laboratory, and pathological examination. The parents of the child are first cousins. A brother and nephew of the mother also had Duchenne type muscular dystrophy. Karyotype analysis in the proband showed both X chromosomes to be morphologically normal. The mother had very high plasma CK levels, equivalent to those observed in carriers of the disease. We discuss different hypothetical mechanisms designed to account for the family pedigree.

We report the case of a

    2-year-old
    AGE

    girl
    GENDER

 who had signs of

    Duchenne type muscular dystrophy
    DIAGNOSIS

 on

    clinical, electromyographic, laboratory, and pathological examination
    PARACLINICAL

.

    The parents of the child are first cousins
    FAMILY

.

    A brother and nephew of the mother also had Duchenne type muscular dystrophy
    FAMILY

.

    Karyotype analysis
    PARACLINICAL

 in the proband showed

    both X chromosomes to be morphologically normal
    NEG_FINDINGS

. The

    mother
    GENDER

 had

    very high plasma CK levels, equivalent to those observed
    BIOCHEMICAL

 in carriers of the disease. We discuss different hypothetical mechanisms designed to account for the family pedigree.


Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm.

A unique combination of a Duchenne-like muscular dystrophy in a girl with a translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome appeared as a result of both gene mutation and chromosome mutation in the mother. The X-autosome rearrangement would permit full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy, in a female, and this would satisfactorily explain the characteristic Duchenne-like course of our patient's illness. The simultaneous de novo appearance of the Duchenne mutation and the X;1 rearrange suggests possible sites for the Duchenne locus on the X chromosome short arm (at Xp1106 or Xp2107).

A unique combination of a

    Duchenne-like muscular dystrophy
    DIAGNOSIS

 in a

    girl
    GENDER

 with a

    translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome
    GENETICS

 appeared as a result of both

    gene mutation
    GENETICS

 and

    chromosome mutation in the mother
    FAMILY

. The

    X-autosome rearrangement
    GENETICS

 would permit

    full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy
    GENETICS

, in a

    female
    GENDER

, and this would satisfactorily explain the

    characteristic Duchenne-like course
    SYMPTOMS

 of our patient's illness. The

    simultaneous de novo appearance of the Duchenne mutation and the X;1 rearrange
    GENETICS

 suggests possible sites

    for the Duchenne locus on the X chromosome short arm (at Xp1106 or Xp2107)
    GENETICS

.


Mechanical ventilation of patients with late stage Duchenne muscular dystrophy: management in the home.

Death in the late stage of Duchenne muscular dystrophy is most frequently a consequence of respiratory failure. Since muscles of ventilation become weakened the bellows mechanism fails insidiously. Patients exhibit symptoms of ventilatory insufficiency, the first to be noticed are those associated with CO2 retention: dyspnea, nightmares, increased heart rate, and increased blood pressure. Ten patients with late stage Duchenne muscular dystrophy have been supplied with mechanical aid for ventilatory assistance. The age of onset of respiratory distress needing mechanical assistance varied from 10 to 20 years. Meaningful survival after allegedly reaching the end stage has been from 2 to 7.5 years with an average of 3.4 years. With a caring family, these patients can have a meaningful life, even though they require continuous mechanical ventilatory aid.

    Death
    SYMPTOMS

 in the late stage of

    Duchenne muscular dystrophy
    DIAGNOSIS

 is most frequently a consequence of

    respiratory failure
    SYMPTOMS

. Since

    muscles of ventilation become weakened
    SYMPTOMS

 the

    bellows mechanism fails insidiously
    SYMPTOMS

. Patients exhibit

    symptoms of ventilatory insufficiency
    SYMPTOMS

, the first to be noticed are those associated with

    CO2 retention
    SYMPTOMS

:

    dyspnea
    SYMPTOMS

,

    nightmares
    SYMPTOMS

,

    increased heart rate
    SYMPTOMS

, and

    increased blood pressure
    SYMPTOMS

. Ten patients with

    late stage Duchenne muscular dystrophy
    DIAGNOSIS

 have been supplied with

    mechanical aid for ventilatory assistance
    MEDICATION

. The

    age of
    AGE

 onset of

    respiratory distress
    SYMPTOMS

 needing

    mechanical assistance
    MEDICATION

 varied

    from 10 to 20 years
    AGE

. Meaningful survival after allegedly reaching the end stage has been

    from 2 to 7.5 years
    AGE

 with an average of

    3.4 years
    AGE

. With a caring family, these patients can have a meaningful life, even though they require

    continuous mechanical ventilatory aid
    MEDICATION

.

Death
respiratory failure
muscles of ventilation become weakened
bellows mechanism fails insidiously
symptoms of ventilatory insufficiency
CO2 retention
dyspnea
nightmares
increased heart rate
increased blood pressure
respiratory distress

Duchenne muscular dystrophy
late stage Duchenne muscular dystrophy


A freeze-fracture study of the plasma membrane of muscle fibres of a patient with chronic creatine kinase elevation suspected for malignant hyperthermia.

The muscle biopsy from a 12-year-old boy with chronic creatine kinase elevation was studied by electron microscopy. At the age of 7 years the patient had a possible abortive attack of malignant hyperthermia. The biopsy specimen contained many fibres with segmental contracture and necrosis; thin sections showed defects of the plasma membrane with loss of glycogen granules into the interstitium. Freeze-fracturing of the plasma membrane showed clustering of intramembranous particles and some membrane areas were devoid of particles and of pinocytotic caveolae. The E-face showed irregular elevations and the P-face corresponding defects. These deviations of the fracture-plane were due to manifest membrane openings, to abnormalities of the structure of the lipid bilayer, to clustering of membrane particles or to the fact that intracellular membranes often were abnormally close to the plasma membrane. The findings suggest that a disintegration of the lipid-protein system of the membrane precedes the formation of manifest defects. The manifest defects resembled those in Duchenne muscular dystrophy. It is unknown whether the changes seen by freeze-fracturing were specific for a myogenic disorder and whether they were due to a basic membrane abnormality or to defects in other systems of the muscle cell.

The

    muscle biopsy
    PARACLINICAL

 from a

    12-year-old
    AGE

    boy
    GENDER

 with

    chronic creatine kinase elevation
    BIOCHEMICAL

 was studied by

    electron microscopy
    PARACLINICAL

. At the

    age of 7 years
    AGE

 the patient had a possible

    abortive attack of malignant hyperthermia
    DIAGNOSIS

. The

    biopsy specimen
    PARACLINICAL

 contained

    many fibres with segmental contracture and necrosis
    MICROSCOPIC

;

    thin sections
    PARACLINICAL

 showed

    defects of the plasma membrane
    MICROSCOPIC

 with

    loss of glycogen granules into the interstitium
    MICROSCOPIC

.

    Freeze-fracturing of the plasma membrane
    PARACLINICAL

 showed

    clustering of intramembranous particles
    MICROSCOPIC

 and

    some membrane areas were devoid of particles and of pinocytotic caveolae
    MICROSCOPIC

. The E-face showed

    irregular elevations and the P-face corresponding defects
    SYMPTOMS

. These

    deviations of the fracture-plane
    SYMPTOMS

 were due to

    manifest membrane openings
    SYMPTOMS

, to

    abnormalities of the structure of the lipid bilayer
    MICROSCOPIC

, to

    clustering of membrane particles
    MICROSCOPIC

 or to the fact that

    intracellular membranes often were abnormally close to the plasma membrane
    MICROSCOPIC

. The findings suggest that a

    disintegration of the lipid-protein system of the membrane
    MICROSCOPIC

 precedes the formation of

    manifest defects
    SYMPTOMS

. The

    manifest defects
    SYMPTOMS

 resembled those in

    Duchenne muscular dystrophy
    DIAGNOSIS

. It is unknown whether the changes seen by

    freeze-fracturing
    PARACLINICAL

 were specific for a

    myogenic disorder
    DIAGNOSIS

 and whether they were due to a basic membrane abnormality or to

    defects in other systems of the muscle cell
    SYMPTOMS

.


Acute hypokalemia as a possible cause of death in a patient with advanced muscular dystrophy.

A patient with advanced muscular dystrophy of the Duchenne type developed severe hypokalemia thought to be secondary to moderate gastro-intestinal losses in association with reduced intracellular potassium stores. With correction of the hypokalemia, the cardiac rhythm became more normal. In patients with advanced dystrophy, hypokalemia may be functionally significant.

A patient with

    advanced muscular dystrophy of the Duchenne type
    DIAGNOSIS

 developed

    severe hypokalemia
    BIOCHEMICAL

 thought to be secondary to

    moderate gastro-intestinal losses
    BIOCHEMICAL

 in association with

    reduced intracellular potassium stores
    BIOCHEMICAL

. With correction of the

    hypokalemia
    BIOCHEMICAL

, the

    cardiac rhythm became more normal
    SYMPTOMS

. In patients with

    advanced dystrophy
    DIAGNOSIS

,

    hypokalemia
    BIOCHEMICAL

 may be functionally significant.

severe hypokalemia
moderate gastro-intestinal losses
reduced intracellular potassium stores
hypokalemia
hypokalemia


Duchenne electrocardiogram in myotonia dystrophica.

The term "myopathic pattern" is applied to the electrocardiographic finding of R/S in lead V1 of more than 1.5 in association with deep Q and prominent R waves in leads V4-V6. Such findings are characteristic of Duchenne's pseudohypertrophic muscular dystrophy and reportedly do not occur in other types of muscular dystrophy or myopathy. The purpose of this paper is to describe a case of myotonia dystrophica with the Duchenne electrocardiographic pattern.

The term "

    myopathic pattern
    SYMPTOMS

" is applied to the electrocardiographic finding of

    R/S in lead V1 of more than 1.5 in association with deep Q and prominent R waves in leads V4-V6
    SYMPTOMS

. Such findings are characteristic of

    Duchenne's pseudohypertrophic muscular dystrophy
    DIAGNOSIS

 and reportedly do not occur in other types of

    muscular dystrophy
    DIAGNOSIS

 or

    myopathy
    DIAGNOSIS

. The purpose of this paper is to describe a case of

    myotonia dystrophica
    DIAGNOSIS

 with the

    Duchenne electrocardiographic pattern
    SYMPTOMS

.


Reproduction in Duchenne dystrophy.

A man with Duchenne muscular dystrophy fathered two living children. He was 1 of 10 affected males in 5 generations. Clinical and genetic patterns, muscle biopsies, autopsy results, and serum enzymes were all compatible with the diagnosis of Duchenne muscular dystrophy. History, blood typing, and karyotypes indicated that he was the biologic father. This report gives confirmatory evidence that Duchenne dystrophy is transmitted as an X-linked defect.

A

    man
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

    fathered two living children
    FAMILY

.

    He
    GENDER

 was 1 of

    10 affected males in 5 generations
    FAMILY

. Clinical and genetic patterns,

    muscle biopsies
    PARACLINICAL

,

    autopsy results
    PARACLINICAL

, and

    serum enzymes
    PARACLINICAL

 were all compatible with the diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

. History,

    blood typing
    PARACLINICAL

, and

    karyotypes
    PARACLINICAL

 indicated that

    he
    GENDER

    was the biologic father
    FAMILY

. This report gives confirmatory evidence that

    Duchenne dystrophy
    DIAGNOSIS

 is

    transmitted as an X-linked defect
    GENETICS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy
Duchenne dystrophy


Duane's retraction syndrome associated with muscular dystrophy.

A case of unilateral type I Duane's syndrome associated with muscular dystrophy is presented. The diagnosis of muscular dystrophy (Duchenne type) is firmly established by clinical, biochemical, electrophysiological, and histological observations. The ocular anomali is clearly distinguished from other congenital disorders of eye movements. The combination of these two congenital anomalities is considered to be quite rare.

A case of

    unilateral type I Duane's syndrome associated with muscular dystrophy
    DIAGNOSIS

 is presented. The diagnosis of

    muscular dystrophy (Duchenne type)
    DIAGNOSIS

 is firmly established by clinical, biochemical, electrophysiological, and

    histological observations
    PARACLINICAL

. The

    ocular anomali
    SYMPTOMS

 is clearly distinguished from other

    congenital disorders of eye movements
    SYMPTOMS

. The

    combination of these two congenital anomalities
    SYMPTOMS

 is considered to be quite rare.


X-linked muscular dystrophy.

X-linked muscular dystrophy has been separated into two types that are generally considered to be distinct entities. We have investigated three families with X-linked muscular dystrophy who demonstrate remarkable intrafamilial variability. In one family 2 brothers with a benign type had a maternal uncle who was affected with the Duchenne type. In another family, 4 members had the benign type but a fifth was much more severely affected than in the classic Duchenne dystrophy; therefore the presence of an "aggressive form" is proposed. A third family also had both benign and severe types. A search of the literature revealed families in which the severe and benign types coexisted. The genetic determinants of this heterogeneity are not yet known. Clinical similarities between benign and severe types of X-linked muscular dystrophy and the presence of families with both types suggest that the two are intimately related.

    X-linked muscular dystrophy
    DIAGNOSIS

 has been separated into two types that are generally considered to be distinct entities. We have investigated three families with

    X-linked muscular dystrophy
    DIAGNOSIS

 who demonstrate remarkable

    intrafamilial variability
    FAMILY

. In one family

    2 brothers with a benign type had a maternal uncle who was affected with the Duchenne type
    FAMILY

. In another

    family, 4 members had the benign type but a fifth was much more severely affected than in the classic Duchenne dystrophy
    FAMILY

; therefore the presence of an "aggressive form" is proposed. A third

    family also had both benign and severe types
    FAMILY

. A search of the literature revealed families in which the

    severe and benign types
    SYMPTOMS

    coexisted
    FAMILY

. The genetic determinants of this heterogeneity are not yet known.

    Clinical similarities between benign and severe types of X-linked muscular dystrophy
    SYMPTOMS

 and the presence of

    families with both
    FAMILY

 types suggest that the two are intimately related.

X-linked muscular dystrophy
X-linked muscular dystrophy


Systolic time intervals in patients with progressive muscular dystrophy of the Duchenne type.

Systolic time intervals (STIs) were measured in 57 patients with progressive muscular dystrophy (PMD) of the Duchenne type, and were correlated with the stages of physical disability. The total electromechanical systole (Q-A2), pre-ejection period (PEP), and left ventricular ejection time (LVET) were corrected for heart rate using the linear regression equations calculated from 91 normal subjects. Each systolic time interval index (STII), i.e. corrected STI, was analyzed. In 15 ambulatory patients (Group P-1), the STIIs did not differ significantly from those in normal controls. In 37 patients who were unable to walk (Group P-2) and 5 patients who were confined to bed (Group P-3), there was a significant increase (p less than 0.001) in the PEP index (PEPI), a decrease (p less than 0.001) in the LVET index (LVETI), and an increase (p less than 0.001) in the PEP/LVET compared with those in controls. The PEPI (p less than 0.001), LVETI (p less than 0.025), and PEP/LVET (p less than 0.001) in Group P-2 differed significantly from those in Group P-1. In Group P-3, the PEPI (p less than 0.005), LVET (p less than 0.001), and PEP/LVET (p less than 0.001) were significantly changed in comparison with those in Group P-2. Remarkable myocardial histopathologic changes suggestive of dystrophy were revealed in autopsies of 3 patients who had been in the severely disabled stage and had shown impaired STIs. It is suggested that cardiac function in patients with moderate to advanced PMD of the Duchenne type is deteriorated in proportion to the disability stages, i.e. the severity of changes in the skeletal muscles.

Systolic time intervals (STIs) were measured in 57 patients with

    progressive muscular dystrophy (PMD) of the Duchenne type
    DIAGNOSIS

, and were correlated with the stages of

    physical disability
    SYMPTOMS

. The

    total electromechanical systole (Q-A2), pre-ejection period (PEP
    SYMPTOMS

), and left ventricular ejection time (LVET) were corrected for heart rate using the linear regression equations calculated from 91 normal subjects. Each systolic time interval index (STII), i.e. corrected STI, was analyzed. In 15 ambulatory patients (Group P-1),

    the STIIs did not differ significantly from those in normal controls
    NEG_FINDINGS

. In 37 patients who were

    unable to walk
    NEG_FINDINGS

 (Group P-2) and 5 patients who were

    confined to bed
    MEDICATION

 (Group P-3), there was a significant increase (p less than 0.001)

    in the PEP index (PEPI)
    SYMPTOMS

, a decrease (p less than 0.001)

    in the LVET index (LVETI)
    SYMPTOMS

, and an increase (p less than 0.001)

    in the PEP/LVET
    SYMPTOMS

 compared with those in controls. The PEPI (p less than 0.001), LVETI (p less than 0.025), and PEP/LVET (p less than 0.001) in Group P-2 differed significantly from those in Group P-1. In Group

    P-3
    DIAGNOSIS

, the PEPI (p less than 0.005), LVET (p less than 0.001), and PEP/LVET (p less than 0.001) were significantly changed in comparison with those in Group P-2.

    Remarkable myocardial histopathologic changes suggestive of dystrophy
    SYMPTOMS

 were revealed in

    autopsies
    PARACLINICAL

 of 3 patients who had been in the severely disabled stage and had shown

    impaired STIs
    SYMPTOMS

. It is suggested that

    cardiac function
    SYMPTOMS

 in patients with

    moderate to advanced PMD of the Duchenne type
    DIAGNOSIS

 is deteriorated in proportion to the disability stages, i.e. the severity of

    changes in the skeletal muscles
    SYMPTOMS

.


The spectrum of mild X-linked recessive muscular dystrophy.

We present 19 patients from 12 families with mild (Becker) X-linked recessive dystrophy and compare them with previously described cases. Features in common in the majority of patients include onset after the age of 7 years, walking beyond the age of 20 to 30 years, mild hypertrophy of the calves, mild joint contractures, and high arched feet. Pshychometric tests, EEGs, and ECGs were usually normal. Muscle biopsy specimens showed a combination of features, some more characteristic of severe (Duchenne) X-linked dystrophy and others more commonly seen in limb girdle dystrophy. Although there was some variation in the severity between different families, within any one kindred, the clinical picture was quite similar.

We present 19 patients from 12 families with

    mild (Becker) X-linked recessive dystrophy
    DIAGNOSIS

 and compare them with previously described cases. Features in common in the majority of patients include

    onset after the age of 7 years
    AGE

,

    walking beyond the age of 20 to 30 years
    SYMPTOMS

,

    mild hypertrophy of the calves
    SYMPTOMS

,

    mild joint contractures
    SYMPTOMS

, and

    high arched feet
    SYMPTOMS

.

    Pshychometric tests, EEGs, and ECGs were usually normal
    NEG_FINDINGS

.

    Muscle biopsy specimens
    PARACLINICAL

 showed a combination of features, some more characteristic of

    severe (Duchenne) X-linked dystrophy
    DIAGNOSIS

 and others more commonly seen in

    limb girdle dystrophy
    DIAGNOSIS

. Although there was some variation in the severity between different families, within any one kindred, the clinical picture was quite similar.


Failure of inactivation of Duchenne dystrophy X-chromosome in one of female identical twins.

Duchenne muscular dystrophy manifested in one of girl twins. The twins were monozygous on the basis of red cell and HL antigens and skin graft compatibility. Karyotyping, including banding techniques, showed a normal number of chromosomes and a normal configuration of the X-chromosome in both twins. The twins were identical in appearance until symptoms of Duchenne dystrophy developed in one at age 4 years. The maternal uncle had classic Duchenne dystrophy; the mother and the nonmanifesting twin showed evidence of being heterozygous for Duchenne dystrophy. The phenotypic difference in monozygous twins is readily explained by lyonization of the X-chromosome after twinning has occurred. The findings substantiate the existence of Duchenne dystrophy manifesting in females with normal karyotypes.

    Duchenne muscular dystrophy
    DIAGNOSIS

 manifested in one of

    girl
    GENDER

 twins. The

    twins were monozygous
    FAMILY

 on the basis of

    red cell and HL antigens
    BIOCHEMICAL

 and

    skin graft compatibility
    SYMPTOMS

.

    Karyotyping
    PARACLINICAL

, including

    banding techniques
    PARACLINICAL

, showed a

    normal number of chromosomes
    NEG_FINDINGS

 and a

    normal configuration of the X-chromosome
    GENETICS

 in both twins. The twins were identical in appearance until

    symptoms of Duchenne dystrophy
    SYMPTOMS

 developed in one at

    age 4 years
    AGE

.

    The maternal uncle had classic Duchenne dystrophy
    FAMILY

;

    the mother and the nonmanifesting twin showed evidence of being heterozygous for Duchenne dystrophy
    FAMILY

. The

    phenotypic difference in monozygous twins
    SYMPTOMS

 is readily explained by

    lyonization of the X-chromosome
    GENETICS

 after

    twinning has occurred
    FAMILY

. The findings substantiate the existence of

    Duchenne dystrophy
    DIAGNOSIS

 manifesting in

    females
    GENDER

 with

    normal karyotypes
    NEG_FINDINGS

.

Duchenne muscular dystrophy
Duchenne dystrophy

normal number of chromosomes
normal karyotypes


Fractures of long bones in Duchenne muscular dystrophy.

The dangers of bed-confininf procedures in children with Duchenne Muscular Dystrophy should be recognized, and their fractures treated so as to encourage continued independent ambulation as long as feasible.

The dangers of

    bed-confininf procedures
    MEDICATION

 in

    children
    AGE

 with

    Duchenne Muscular Dystrophy
    DIAGNOSIS

 should be recognized, and their fractures treated so as to encourage

    continued independent ambulation
    MEDICATION

 as long as feasible.

bed-confininf procedures
continued independent ambulation


Hand dominance and scoliosis in Duchenne muscular dystrophy.

Twenty-three patients with Duchenne muscular dystrophy and scoliosis were studied. In all but one patient the major convexity was to the side of the dominant hand. The unsupported growing spine is easily unbalanced by asymmetrical forces imposed on it. From our observations we believe major use of a single upper extremity will result in scoliosis with the major convexity toward the side of the dominant hand. Management should include counterbalancing the postural abnormality imposed by hand dominance as well as unloading the spine frequently during the patient's waking hours.

Twenty-three patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    scoliosis
    DIAGNOSIS

 were studied. In all but one patient the

    major convexity was to the side of the dominant hand
    SYMPTOMS

. The

    unsupported growing spine is easily unbalanced by asymmetrical forces imposed on it
    SYMPTOMS

. From our observations we believe

    major use of a single upper extremity
    MEDICATION

 will result in

    scoliosis with the major convexity toward the side of the dominant hand
    SYMPTOMS

. Management should include

    counterbalancing the postural abnormality imposed by hand dominance
    SYMPTOMS

 as well as

    unloading the spine frequently
    MEDICATION

 during the patient's waking hours.

major use of a single upper extremity
unloading the spine frequently


[Duchenne muscular dystrophy in girls (author's transl)].

The AA., after a review cases of girls suffering from a muscular dystrophy like Duchenne, present two cases that they think to set in the same nosographical context. Even though they admit its extreme rarity and the possiblility that many cases previously published are controversial, they accept that Duchenne myodistrophic syndromes certainly occur in girls, even if their substantial nature remain uncertain.

The AA., after a review cases of

    girls
    GENDER

 suffering from a

    muscular dystrophy like Duchenne
    DIAGNOSIS

, present two cases that they think to set in the same nosographical context. Even though they admit its extreme rarity and the possiblility that many cases previously published are controversial, they accept that

    Duchenne myodistrophic syndromes
    DIAGNOSIS

 certainly occur in

    girls
    GENDER

, even if their substantial nature remain uncertain.

muscular dystrophy like Duchenne
Duchenne myodistrophic syndromes


Duchenne muscular dystrophy and poliomyelitis. A study of dystrophic-denervated muscle.

A systematic study of dystrophy-denervation in human muscle showed minimal morphometabolic differences between dystrophic and dystrophic-denervated muscle. The only certain conclusion is that denervation influences the rhythm of evolution of the dystrophy without impressing any of the few characteristics considered at present as peculiar to denervation.

A systematic study of

    dystrophy-denervation
    DIAGNOSIS

 in

    human muscle
    PARACLINICAL

 showed

    minimal morphometabolic differences between dystrophic and dystrophic-denervated muscle
    SYMPTOMS

. The only certain conclusion is that

    denervation
    MEDICATION

 influences the rhythm of evolution of the

    dystrophy
    DIAGNOSIS

    without impressing any of
    NEG_FINDINGS

 the few characteristics considered at present as peculiar to

    denervation
    NEG_FINDINGS

.


Muscular dystrophy in young girls.

Muscular dystrophy occurred in four girls. In only one of these was the syndrome both proximal and with pseudo-hypertrophy, thus clinically resembling the x-linked Duchenne type of the disease. The evidence for a primary dystrophic process existing in the four individuals is based on the laboratory findings of very high serum creatine kinase levels, myopathic E.M.G. appearances and muscle biopsies. However, each case is clinically different (one is proximal with contractures, another limb girdle with facial involvement and the fourth is distal) and worthy of documentation. The recent demonstration of a neurogenic basis for several myopathies previously considered to be dystrophic in nature has not caused us to revise our view that true muscular dystrophy does occur in girls but that the "Duchenne-like" type is rare.

    Muscular dystrophy
    DIAGNOSIS

 occurred in four

    girls
    GENDER

. In only one of these was the

    syndrome both proximal and with pseudo-hypertrophy
    SYMPTOMS

, thus clinically resembling the

    x-linked Duchenne type of the disease
    GENETICS

. The evidence for a

    primary dystrophic process
    DIAGNOSIS

 existing in the four individuals is based on the laboratory findings of

    very high serum creatine kinase levels
    BIOCHEMICAL

,

    myopathic E.M.G. appearances
    SYMPTOMS

 and

    muscle biopsies
    PARACLINICAL

. However, each case is clinically different (one is

    proximal with contractures
    SYMPTOMS

, another

    limb girdle with facial involvement
    SYMPTOMS

 and the fourth is distal) and worthy of documentation. The recent demonstration of a neurogenic basis for several

    myopathies
    DIAGNOSIS

    previously considered to be dystrophic in nature
    NEG_FINDINGS

 has not caused us to revise our view that

    true muscular dystrophy
    DIAGNOSIS

 does occur in

    girls
    GENDER

 but that the "

    Duchenne-like" type
    DIAGNOSIS

 is rare.

Muscular dystrophy
primary dystrophic process
myopathies
true muscular dystrophy
Duchenne-like" type


Step-by-step typing for the accurate diagnosis of concurrent light chain and transthyretin cardiac amyloidosis.

While 99m Tc-pyrophosphate scintigraphy is clearly useful in diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM), it is necessary to know the pitfalls of this test for proper use. We present a rare case of concurrent ATTR-CM and amyloid light chain (AL) cardiomyopathy. The patient showed congestive heart failure with left ventricular hypertrophy. 99m Tc-pyrophosphate scintigraphy revealed abnormal cardiac uptake of Grade 3, a typical feature for ATTR-CM. However, the patient showed renal impairment with proteinuria and the presence of monoclonal gammopathy, which rather suggested AL amyloidosis. Endomyocardial biopsy, immunohistochemistry, and proteomic analysis by laser microdissection with liquid chromatography-coupled tandem mass spectrometry were performed, which finally confirmed both ATTR-CM and AL cardiomyopathy. This case implicates the importance of combining examinations and precisely interpreting the results to diagnose cardiac amyloidosis accurately.

While

    99m Tc-pyrophosphate scintigraphy
    PARACLINICAL

 is clearly useful in diagnosing

    transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

, it is necessary to know the pitfalls of this test for proper use. We present a rare case of

    concurrent ATTR-CM and amyloid light chain (AL) cardiomyopathy
    DIAGNOSIS

. The patient showed

    congestive heart failure
    SYMPTOMS

 with

    left ventricular hypertrophy
    SYMPTOMS

.

    99m Tc-pyrophosphate scintigraphy
    PARACLINICAL

 revealed

    abnormal cardiac uptake of Grade 3, a typical feature for ATTR-CM
    SYMPTOMS

. However, the patient showed

    renal impairment
    SYMPTOMS

 with

    proteinuria
    BIOCHEMICAL

 and the presence of

    monoclonal gammopathy
    BIOCHEMICAL

, which rather suggested

    AL amyloidosis
    DIAGNOSIS

.

    Endomyocardial biopsy
    PARACLINICAL

,

    immunohistochemistry
    PARACLINICAL

, and

    proteomic analysis by laser microdissection with liquid chromatography-coupled tandem mass spectrometry
    PARACLINICAL

 were performed, which finally confirmed

    both ATTR-CM and AL cardiomyopathy
    DIAGNOSIS

. This case implicates the importance of combining examinations and precisely interpreting the results to diagnose

    cardiac amyloidosis
    DIAGNOSIS

 accurately.


A Case of Early Hereditary Transthyretin Amyloid Cardiomyopathy Recognition With Genetic Screening: A Case Report.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is one of the most common types of cardiac amyloidosis. Amyloid cardiomyopathy more commonly affects men, elderly, and 3% to 4% of the African-American population. ATTR-CM suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of ATTR-CM relies on the presence of heart failure, red flag signs and symptoms, and age >65 or >70 for men and women respectively. Little is known about cases when it presents in early ages. Case: We report a 62-year-old African American male with past medical history of hyperlipidemia, prostate cancer, hypertension, bilateral carpal tunnel surgery that had debuted with a cardiac arrhythmia at age 55 and was diagnosed with heart failure several years later. Restrictive cardiomyopathy was suspected, and genetic screening was sent for ATTRm which confirmed a pathogenic trasnthyretin gene mutation. Endomyocardial biopsy was performed which confirmed cardiac amyloid deposition. Discussion: ATTR-CM is a rare disease with an increasing prevalence. Cases with out of proportion signs and symptoms of heart failure with preserved ejection fractions should raise the suspicion of ATTR-CM despite age.

Background:

    Transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

 is one of the most common types of

    cardiac amyloidosis
    DIAGNOSIS

.

    Amyloid cardiomyopathy
    DIAGNOSIS

 more commonly affects

    men
    GENDER

,

    elderly
    AGE

, and 3% to 4% of the

    African-American
    ETHNICITY

 population.

    ATTR-CM
    DIAGNOSIS

 suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of

    ATTR-CM
    DIAGNOSIS

 relies on the presence of

    heart failure
    SYMPTOMS

,

    red flag signs and symptoms
    SYMPTOMS

, and

    age >65 or >70
    AGE

 for

    men
    GENDER

 and

    women
    GENDER

 respectively. Little is known about cases when it presents in

    early ages
    AGE

. Case: We report a

    62-year-old
    AGE

    African American
    ETHNICITY

    male
    GENDER

 with past medical history of

    hyperlipidemia
    SYMPTOMS

,

    prostate cancer
    DIAGNOSIS

,

    hypertension
    SYMPTOMS

,

    bilateral carpal tunnel surgery
    MEDICATION

 that had debuted with a

    cardiac arrhythmia
    SYMPTOMS

 at

    age 55
    AGE

 and was diagnosed with

    heart failure
    SYMPTOMS

 several years later.

    Restrictive cardiomyopathy
    DIAGNOSIS

 was suspected, and

    genetic screening
    PARACLINICAL

 was sent for

    ATTRm
    DIAGNOSIS

 which confirmed a

    pathogenic trasnthyretin gene mutation
    GENETICS

.

    Endomyocardial biopsy
    PARACLINICAL

 was performed which confirmed

    cardiac amyloid deposition
    MICROSCOPIC

. Discussion:

    ATTR-CM
    DIAGNOSIS

 is a rare disease with an increasing prevalence. Cases with

    out of proportion signs and symptoms of heart failure
    SYMPTOMS

 with

    preserved ejection fractions
    SYMPTOMS

 should raise the suspicion of

    ATTR-CM
    DIAGNOSIS

    despite age
    AGE

.


Preclinical diagnosis of wild-type transthyretin amyloid cardiomyopathy in a patient undergoing carpal tunnel release.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) has received increased attention because of its novel treatment options. Carpal tunnel syndrome (CTS) is known as early symptoms in transthyretin amyloidosis (ATTR) preceding cardiac involvement and one of the "red flags" for ATTR-CM. A 64-year-old man underwent carpal tunnel release for carpal tunnel syndrome at 62 years. He was diagnosed with wild-type ATTR due to deposition of transthyretin (TTR) amyloid in flexor tenosynovium specimens and no TTR gene mutation. Examination for detection of cardiac involvement was performed after the operation, and there were no definitive findings of ATTR-CM; however, an early stage of ATTR-CM remained a possibility. Serial image evaluation and biomarker analysis revealed positive findings for ATTR-CM, and we performed an endomyocardial biopsy, resulting in the detection of amyloid deposition. He was diagnosed with ATTRwt-CM 2 years after the operation, and even then, he had no heart failure symptoms. Early diagnosis and treatment are important for the improvement of clinical outcomes in patients with ATTRwt-CM. TTR deposition in the ligaments or tendons is often observed in patients with CTS and should be considered at high risk of future ATTR-CM. Serial follow-up of these patients may enable the diagnosis of preclinical ATTR-CM. <Learning objective: Bilateral carpal tunnel syndrome (CTS) patients with transthyretin deposition in surgically-excised specimens are considered to be at high risk of future transthyretin amyloid cardiomyopathy (ATTR-CM). Serial evaluation of imaging results and cardiac biomarkers are useful for the diagnosis of preclinical ATTR-CM.>.

    Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM)
    DIAGNOSIS

 has received increased attention because of its novel treatment options.

    Carpal tunnel syndrome (CTS)
    SYMPTOMS

 is known as early symptoms in

    transthyretin amyloidosis (ATTR)
    DIAGNOSIS

 preceding

    cardiac involvement
    SYMPTOMS

 and one of the "red flags" for

    ATTR-CM
    DIAGNOSIS

. A

    64-year-old
    AGE

    man
    GENDER

 underwent

    carpal tunnel release
    MEDICATION

 for

    carpal tunnel syndrome
    DIAGNOSIS

 at

    62 years
    AGE

.

    He
    GENDER

 was diagnosed with

    wild-type ATTR
    DIAGNOSIS

 due to

    deposition of transthyretin (TTR) amyloid in flexor tenosynovium specimens
    MICROSCOPIC

 and

    no TTR gene mutation
    NEG_FINDINGS

.

    Examination for detection of cardiac involvement
    PARACLINICAL

 was performed after the

    operation
    MEDICATION

, and there were

    no definitive findings of ATTR-CM
    NEG_FINDINGS

; however, an

    early stage of ATTR-CM
    DIAGNOSIS

 remained a possibility.

    Serial image evaluation
    PARACLINICAL

 and

    biomarker analysis
    PARACLINICAL

 revealed

    positive findings for ATTR-CM
    SYMPTOMS

, and we performed an

    endomyocardial biopsy
    PARACLINICAL

, resulting in the detection of

    amyloid deposition
    MICROSCOPIC

.

    He
    GENDER

 was diagnosed with

    ATTRwt-CM
    DIAGNOSIS

 2 years after the operation, and even then,

    he
    GENDER

 had

    no heart failure symptoms
    NEG_FINDINGS

. Early diagnosis and treatment are important for the improvement of clinical outcomes in patients with

    ATTRwt-CM
    DIAGNOSIS

.

    TTR deposition in the ligaments or tendons
    MICROSCOPIC

 is often observed in patients with

    CTS
    DIAGNOSIS

 and should be considered at high risk of future

    ATTR-CM
    DIAGNOSIS

.

    Serial follow-up
    PARACLINICAL

 of these patients may enable the diagnosis of

    preclinical ATTR-CM
    DIAGNOSIS

. <Learning objective:

    Bilateral carpal tunnel syndrome (CTS)
    DIAGNOSIS

 patients with

    transthyretin deposition in surgically-excised specimens
    MICROSCOPIC

 are considered to be at high risk of future

    transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

.

    Serial evaluation of imaging results and cardiac biomarkers
    PARACLINICAL

 are useful for the diagnosis of

    preclinical ATTR-CM
    DIAGNOSIS

.>.

Carpal tunnel syndrome (CTS)
cardiac involvement
positive findings for ATTR-CM

no TTR gene mutation
no definitive findings of ATTR-CM
no heart failure symptoms


Genome silencer therapy leading to 'regression' of cardiac amyloid load on cardiovascular magnetic resonance: a case report.

Hereditary or variant transthyretin amyloidosis (ATTRv) is a progressive disease manifesting with neuropathy and/or cardiomyopathy. An early and accurate diagnosis of cardiac amyloidosis is a pre-requisite for timely and appropriate patient management, including anti-amyloid therapies, as it is associated with heart failure, conduction disease, and arrhythmias, leading to reduced quality of life and early death.

We present the case of an ATTRv male patient presenting with a mixed amyloidosis phenotype (neuropathy and cardiomyopathy). Cardiac disease manifestation comprised tachyarrhythmias (atrial fibrillation) and conduction abnormalities (atrio-ventricular block) in addition to segmental left ventricular (LV) hypertrophy (septal wall) due to regionally pronounced amyloid deposits in the basal LV myocardium. Interestingly, by means of serial cardiovascular magnetic resonance (CMR) studies, we were able to demonstrate an impressive and unexpected improvement of cardiomyopathy findings within a relatively short period-of-time after the implementation of genome-silencer therapies.

This is our second case report that showed ATTRv cardiomyopathy reversal under anti-amyloid therapy-documented by multi-parametric CMR. Our findings support the hypothesis that amyloid infiltration leading to cardiomyopathy is not an irreversible pathological process-but rather a dynamic one, that cannot only be stopped but even reversed (to a certain degree) by currently emerging anti-amyloid therapies. Moreover, the role of serial multi-parametric CMR imaging for surveillance of cardiomyopathy dynamics under these therapies is nicely illustrated.

    Hereditary or variant transthyretin amyloidosis (ATTRv)
    DIAGNOSIS

 is a progressive disease manifesting with

    neuropathy
    SYMPTOMS

 and/or

    cardiomyopathy
    SYMPTOMS

. An early and accurate diagnosis of

    cardiac amyloidosis
    DIAGNOSIS

 is a pre-requisite for timely and appropriate patient management, including

    anti-amyloid therapies
    MEDICATION

, as it is associated with

    heart failure
    SYMPTOMS

,

    conduction disease
    SYMPTOMS

, and

    arrhythmias
    SYMPTOMS

, leading to

    reduced quality of life
    SYMPTOMS

 and

    early death
    SYMPTOMS

.

We present the case of an

    ATTRv
    DIAGNOSIS

    male
    GENDER

 patient presenting with a

    mixed amyloidosis phenotype (neuropathy and cardiomyopathy)
    DIAGNOSIS

.

    Cardiac disease
    SYMPTOMS

 manifestation comprised

    tachyarrhythmias (atrial fibrillation)
    SYMPTOMS

 and

    conduction abnormalities (atrio-ventricular block)
    SYMPTOMS

 in addition to

    segmental left ventricular (LV) hypertrophy (septal wall)
    SYMPTOMS

 due to

    regionally pronounced amyloid deposits in the basal LV myocardium
    MICROSCOPIC

. Interestingly, by means of

    serial cardiovascular magnetic resonance (CMR) studies
    PARACLINICAL

, we were able to demonstrate an

    impressive and unexpected improvement of cardiomyopathy findings
    SYMPTOMS

 within a relatively short period-of-time after the implementation of

    genome-silencer therapies
    MEDICATION

.

This is our second case report that showed

    ATTRv cardiomyopathy reversal
    DIAGNOSIS

 under

    anti-amyloid therapy
    MEDICATION

-documented by

    multi-parametric CMR
    PARACLINICAL

. Our findings support the hypothesis that

    amyloid infiltration
    MICROSCOPIC

 leading to

    cardiomyopathy
    DIAGNOSIS

 is not an irreversible pathological process-but rather a dynamic one, that cannot only be stopped but even reversed (to a certain degree) by currently emerging

    anti-amyloid therapies
    MEDICATION

. Moreover, the role of

    serial multi-parametric CMR imaging
    PARACLINICAL

 for surveillance of

    cardiomyopathy
    SYMPTOMS

 dynamics under these therapies is nicely illustrated.

anti-amyloid therapies
genome-silencer therapies
anti-amyloid therapy
anti-amyloid therapies


Wild type transthyretin cardiac amiloidozis as a rare and overlooked underlying etiology in a patient with heart failure with preserved ejection fraction and left ventricular hypertrophy.

Cardiac amyloidosis (CA) is a rare, progressive, infiltrative and restrictive cardiomyopathy characterized by extracellular deposition of insoluble amyloid fibrils in the form of misfolded endogenous proteins in the heart. The most common types of CA are transthyretin (TTR) and immunoglobulin light chain (AL) amyloidosis. TTR-CA is further subdivided into wild-type (wtTTR-CA) and mutant (mTTR-CA) forms. CA has long been thought to be a rare disease. However, in clinical practice, it is frequently overlooked, but increasingly recognized as the cause of heart failure with preserved ejection fraction (HFpEF). Patients with CA show poor prognosis. Early diagnosis and novel therapeutic options have been shown to significantly improve prognosis. Novel diagnostic modalities such as nuclear scintigraphy allow the earlier diagnosis of TTR-CA without a biopsy. In this report, we present a case of wtTTR-CA as a rare and overlooked underlying etiology of HFpEF and left ventricular hypertrophy.

    Cardiac amyloidosis (CA)
    DIAGNOSIS

 is a rare, progressive,

    infiltrative and restrictive cardiomyopathy
    DIAGNOSIS

 characterized by

    extracellular deposition of insoluble amyloid fibrils in the form of misfolded endogenous proteins in the heart
    MICROSCOPIC

. The most common types of

    CA
    DIAGNOSIS

 are

    transthyretin (TTR) and immunoglobulin light chain (AL) amyloidosis
    DIAGNOSIS

.

    TTR-CA
    DIAGNOSIS

 is further subdivided into

    wild-type (wtTTR-CA)
    GENETICS

 and mutant

    (mTTR-CA)
    DIAGNOSIS

 forms.

    CA
    DIAGNOSIS

 has long been thought to be a rare disease. However, in clinical practice, it is frequently overlooked, but increasingly recognized as the cause of

    heart failure with preserved ejection fraction
    SYMPTOMS

 (

    HFpEF
    SYMPTOMS

). Patients with

    CA
    DIAGNOSIS

 show poor prognosis. Early diagnosis and novel therapeutic options have been shown to significantly improve prognosis. Novel diagnostic modalities such as

    nuclear scintigraphy
    PARACLINICAL

 allow the earlier diagnosis of

    TTR-CA
    DIAGNOSIS

 without a

    biopsy
    PARACLINICAL

. In this report, we present a case of

    wtTTR-CA
    DIAGNOSIS

 as a rare and overlooked underlying etiology of

    HFpEF
    DIAGNOSIS

 and

    left ventricular hypertrophy
    SYMPTOMS

.


A challenging road to diagnosing transthyretin cardiac amyloidosis and using technetium-99m pyrophosphate bone scintigraphy in nuclear cardiology - A case report.

Cardiac amyloidosis (CA) is a rare form of protein deposition disease, leading to restrictive cardiomyopathy that often presents with signs and symptoms of unexplained heart failure with preserved ejection fraction (HFpEF). There are two main subtypes of CA, namely light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), which are conventionally confirmed by endomyocardial biopsy (EMB). The prognosis and treatment of the subtypes differ extensively, making it crucial to distinguish between the two. Although echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) are useful to aid in the diagnosis, they are unable to differentiate between the subtypes. Advantageously, the transthyretin cardiac amyloidosis (ATTR-CA) subtype can be diagnosed based on nuclear medicine bone scintigraphy imaging using Technetiumlabelled bone-seeking radiotracers. We report a case of a previously well, elderly gentleman who presented with acute heart failure symptoms, whereby ECHO findings were suspicious for CA. Technetium-99m pyrophosphate (99mTc- PYP) bone scintigraphy performed with complementary single photon emission computed tomography/computed tomography (SPECT/CT) at three hours post-injection revealed radiotracer uptake in the myocardium that was higher than the skeletal bone uptake. This corresponded to Perugini score of 3 along with an increased heart to contralateral lung ratio (H:CL) of 1.69. The bone scintigraphy findings together with his symptoms, ECHO, CMR, and laboratory results enabled the diagnosis of ATTR-CA to be made. In summary, bone scintigraphy offers a reliable and non-invasive method for the diagnosis of ATTR-CA. We also highlight the diagnostic pitfalls and recommendations in reporting bone scintigraphy for the indication of typing cardiac amyloidosis.

    Cardiac amyloidosis (CA)
    DIAGNOSIS

 is a rare form of

    protein deposition disease
    DIAGNOSIS

, leading to

    restrictive cardiomyopathy
    DIAGNOSIS

 that often presents with

    signs and symptoms of unexplained heart failure with preserved ejection fraction (HFpEF)
    SYMPTOMS

. There are two main subtypes of

    CA
    DIAGNOSIS

, namely

    light chain amyloidosis (AL)
    DIAGNOSIS

 and

    transthyretin amyloidosis (ATTR)
    DIAGNOSIS

, which are conventionally confirmed by

    endomyocardial biopsy (EMB)
    PARACLINICAL

. The prognosis and treatment of the subtypes differ extensively, making it crucial to distinguish between the two. Although

    echocardiography (ECHO)
    PARACLINICAL

 and

    cardiac magnetic resonance imaging (CMR)
    PARACLINICAL

 are useful to aid in the diagnosis, they are unable to differentiate between the subtypes. Advantageously, the

    transthyretin cardiac amyloidosis (ATTR-CA) subtype
    DIAGNOSIS

 can be diagnosed based on

    nuclear medicine bone scintigraphy imaging
    PARACLINICAL

 using

    Technetiumlabelled bone-seeking radiotracers
    PARACLINICAL

. We report a case of a previously well,

    elderly
    AGE

    gentleman
    GENDER

 who presented with

    acute heart failure symptoms
    SYMPTOMS

, whereby

    ECHO findings were suspicious for CA
    SYMPTOMS

.

    Technetium-99m pyrophosphate (99mTc- PYP) bone scintigraphy performed with complementary single photon emission computed tomography/computed tomography (SPECT/CT) at three hours post-injection
    PARACLINICAL

 revealed

    radiotracer uptake in the myocardium that was higher than the skeletal bone uptake
    SYMPTOMS

. This corresponded to

    Perugini score of 3
    SYMPTOMS

 along with an

    increased heart to contralateral lung ratio (H:CL) of 1.69
    SYMPTOMS

. The

    bone scintigraphy
    PARACLINICAL

 findings together with his symptoms,

    ECHO
    PARACLINICAL

,

    CMR
    PARACLINICAL

, and

    laboratory results
    PARACLINICAL

 enabled the diagnosis of

    ATTR-CA
    DIAGNOSIS

 to be made. In summary,

    bone scintigraphy
    PARACLINICAL

 offers a reliable and non-invasive method for the diagnosis of

    ATTR-CA
    DIAGNOSIS

. We also highlight the diagnostic pitfalls and recommendations in reporting

    bone scintigraphy
    PARACLINICAL

 for the indication of

    typing cardiac amyloidosis
    DIAGNOSIS

.


Ruptured Bullae: A Case of Transthyretin Cardiac Amyloidosis.

Amyloidosis is a rare disease with an incidence of only 16.6 per 100,000 patients per year. A high grade of clinical suspicion is required to suspect an atypical cause of left ventricular hypertrophy or new-onset heart failure. A transthoracic echocardiogram (TTE) is the initial evaluation that may yield clues pointing towards an etiology of cardiac amyloidosis. Due to the subjective nature of TTE interpretations, suspicion for cardiac amyloidosis may be missed. Once suspicion arises, additional tests, such as serum and urine electrophoresis and technetium-99m pyrophosphate myocardial perfusion imaging, can further aid in establishing a diagnosis. The pathophysiology in transthyretin amyloidosis (ATTR) involves the misfolding of the transthyretin/prealbumin protein, which leads to an inherent propensity to aggregate. These proteins can accumulate in the extracellular space between cardiac myocytes, which may thicken sections of the heart, leading to ventricular restriction. Here, we explore the case of an 83-year-old man with chronic, treatment-resistant heart failure with preserved ejection fraction, New York Heart Association class III, who presented with multiple ruptured bullae in the bilateral lower extremity, leading to a new diagnosis of ATTR cardiac amyloidosis.

    Amyloidosis
    DIAGNOSIS

 is a rare disease with an incidence of only 16.6 per 100,000 patients per year. A high grade of clinical suspicion is required to suspect an atypical cause of

    left ventricular hypertrophy
    SYMPTOMS

 or

    new-onset heart failure
    SYMPTOMS

. A

    transthoracic echocardiogram (TTE)
    PARACLINICAL

 is the initial evaluation that may yield clues pointing towards an etiology of

    cardiac amyloidosis
    DIAGNOSIS

. Due to the subjective nature of

    TTE interpretations
    PARACLINICAL

, suspicion for

    cardiac amyloidosis
    DIAGNOSIS

 may be missed. Once suspicion arises, additional tests, such as

    serum and urine electrophoresis
    PARACLINICAL

 and

    technetium-99m pyrophosphate myocardial perfusion imaging
    PARACLINICAL

, can further aid in establishing a diagnosis. The pathophysiology in

    transthyretin amyloidosis (ATTR)
    DIAGNOSIS

 involves the

    misfolding of the transthyretin/prealbumin protein
    MICROSCOPIC

, which leads to an inherent

    propensity to aggregate
    MICROSCOPIC

.

    These proteins can accumulate in the extracellular space between cardiac myocytes
    MICROSCOPIC

, which may

    thicken sections of the heart
    SYMPTOMS

, leading to

    ventricular restriction
    SYMPTOMS

. Here, we explore the case of an

    83-year-old
    AGE

    man
    GENDER

 with

    chronic, treatment-resistant heart failure
    DIAGNOSIS

 with

    preserved ejection fraction
    SYMPTOMS

,

    New York Heart Association class III
    SYMPTOMS

, who presented with

    multiple ruptured bullae in the bilateral lower extremity
    SYMPTOMS

, leading to a new diagnosis of

    ATTR cardiac amyloidosis
    DIAGNOSIS

.


Hereditary Apolipoprotein A-I-Associated Cardiac Amyloidosis: Importance of Endomyocardial Biopsy When Suspicion Remains High.

Cardiac amyloidosis has recently garnered substantial attention. Although the advent of noninvasive diagnostic algorithms revolutionized diagnosis, endomyocardial biopsy may still be considered in select cases to determine the amyloidosis subtype definitively. We report a case of a patients with a known mutation causing hereditary apolipoprotein A-I-associated cardiac amyloidosis. (Level of Difficulty: Advanced.).

    Cardiac amyloidosis
    DIAGNOSIS

 has recently garnered substantial attention. Although the advent of noninvasive diagnostic algorithms revolutionized diagnosis,

    endomyocardial biopsy
    PARACLINICAL

 may still be considered in select cases to determine the

    amyloidosis
    DIAGNOSIS

 subtype definitively. We report a case of a patients with a known

    mutation causing hereditary apolipoprotein A-I-associated cardiac amyloidosis
    GENETICS

. (Level of Difficulty: Advanced.).


Early-Onset of Transthyretin Amyloidosis in a Young Afro-Caribbean Woman With Thr60Ala Mutation.

Transthyretin amyloidosis involves the deposition of transthyretin amyloid fibrils in the body. We report an unusual case of a young Afro-Caribbean woman harboring a Thr60Ala mutation who presented with clinical signs of heart failure and polyneuropathy confirmed with genetic testing and results of an abdominal fat pad biopsy. (Level of Difficulty: Intermediate.).

    Transthyretin amyloidosis
    DIAGNOSIS

 involves the

    deposition of transthyretin amyloid fibrils in the body
    MICROSCOPIC

. We report an unusual case of a

    young
    AGE

    Afro-Caribbean
    ETHNICITY

    woman
    GENDER

 harboring a

    Thr60Ala mutation
    GENETICS

 who presented with

    clinical signs of heart failure
    SYMPTOMS

 and

    polyneuropathy
    DIAGNOSIS

 confirmed with

    genetic testing
    PARACLINICAL

 and results of an

    abdominal fat pad biopsy
    PARACLINICAL

. (Level of Difficulty: Intermediate.).


Trajectory of left ventricular geometry and diastolic dysfunction in hereditary transthyretin cardiac amyloidosis.

Amyloid transthyretin (ATTR) depositions cause left ventricular (LV) hypertrophy, diastolic dysfunction, and heart failure. The time course of changes in LV geometry and diastolic dysfunction has not been fully reported in patients with ATTR cardiomyopathy. A 79-year-old woman with previous myocardial infraction presented with shortness of breath on exertion, and progressive bilateral lower extremity weakness and polyneuropathy. She was diagnosed with Val30Met hereditary ATTR cardiomyopathy by cardiac biopsy and genetic testing. During the past 5 year period, significant LV concentric remodelling with small LV cavity occurred, resulting in an increased LV stiffness and prolonged LV relaxation. This case report highlights the time course of changes in LV geometry and diastolic function and the importance of early diagnosis of ATTR cardiomyopathy.

    Amyloid transthyretin (ATTR) depositions
    MICROSCOPIC

 cause

    left ventricular (LV) hypertrophy
    SYMPTOMS

,

    diastolic dysfunction
    SYMPTOMS

, and

    heart failure
    SYMPTOMS

. The time course of changes in LV geometry and

    diastolic dysfunction
    SYMPTOMS

 has not been fully reported in patients with

    ATTR cardiomyopathy
    DIAGNOSIS

. A

    79-year-old
    AGE

    woman
    GENDER

 with previous

    myocardial infraction
    SYMPTOMS

 presented with

    shortness of breath on exertion
    SYMPTOMS

, and

    progressive bilateral lower extremity weakness
    SYMPTOMS

 and

    polyneuropathy
    SYMPTOMS

.

    She
    GENDER

 was diagnosed with

    Val30Met hereditary ATTR cardiomyopathy
    DIAGNOSIS

 by

    cardiac biopsy
    PARACLINICAL

 and

    genetic testing
    PARACLINICAL

. During the past 5 year period,

    significant LV concentric remodelling with small LV cavity
    SYMPTOMS

 occurred, resulting in an

    increased LV stiffness
    SYMPTOMS

 and

    prolonged LV relaxation
    SYMPTOMS

. This case report highlights the time course of changes in

    LV geometry and diastolic function
    SYMPTOMS

 and the importance of early diagnosis of

    ATTR cardiomyopathy
    DIAGNOSIS

.

ATTR cardiomyopathy
Val30Met hereditary ATTR cardiomyopathy
ATTR cardiomyopathy


Cardiac Amyloidosis-Challenging Diagnosis and Unclear Clinical Picture.

Cardiac amyloidosis (CA) is a rare systemic disease determined by the extracellular deposition of amyloid protein in the heart. The protein can accumulate in any part of the heart: myocardium, vessels, endocardium, valves, epicardium and parietal pericardium. The types of CA include the following types: light chain (AL), amyloidosis AA (Amyloid A) and transthyretin (ATTR). The detection of specific subtypes remains of great importance to implement the targeted treatment. We present the case of a 65-year-old woman, who was admitted with severe deterioration of exercise capacity, a bilateral reduction of physiological vesicular murmur, ascites and edema of lower extremities. CA was suspected due to echocardiographic examination results, which led to further examination and final diagnosis. The aim of this study is to improve the disease awareness among clinicians and shorten the delay between the first symptoms and the diagnosis establishment resulting in a better outcome.

    Cardiac amyloidosis (CA)
    DIAGNOSIS

 is a

    rare systemic disease
    DIAGNOSIS

 determined by the

    extracellular deposition of amyloid protein in the heart
    MICROSCOPIC

. The

    protein can accumulate in any part of the heart: myocardium, vessels, endocardium, valves, epicardium and parietal pericardium
    MICROSCOPIC

. The types of

    CA
    DIAGNOSIS

 include the following types:

    light chain (AL)
    DIAGNOSIS

,

    amyloidosis AA (Amyloid A)
    DIAGNOSIS

 and

    transthyretin (ATTR)
    DIAGNOSIS

. The detection of specific subtypes remains of great importance to implement the targeted treatment. We present the case of a

    65-year-old
    AGE

    woman
    GENDER

, who was admitted with

    severe deterioration of exercise capacity
    SYMPTOMS

, a

    bilateral reduction of physiological vesicular murmur
    SYMPTOMS

,

    ascites
    SYMPTOMS

 and

    edema of lower extremities
    SYMPTOMS

.

    CA
    DIAGNOSIS

 was suspected due to

    echocardiographic examination
    PARACLINICAL

 results, which led to further examination and final diagnosis. The aim of this study is to improve the disease awareness among clinicians and shorten the delay between the first symptoms and the diagnosis establishment resulting in a better outcome.

Cardiac amyloidosis (CA)
rare systemic disease
CA
light chain (AL)
amyloidosis AA (Amyloid A)
transthyretin (ATTR)
CA


Noninvasive Diagnostic Modalities in an Isolated Case of Cardiac Amyloidosis.

Amyloidoses are a family of inherited or acquired disorders characterized by the deposition of insoluble extracellular protein fibrils in various organs and tissues, thereby impairing their function. Amyloidoses are typically misfolded proteins, and on rare occasions, can deposit in the myocardium resulting in an infiltrative/restrictive cardiomyopathy. Restrictive cardiomyopathy is an underdiagnosed cause of congestive heart failure (CHF) with preserved ejection fraction, atrial and ventricular arrhythmias along with conduction defects. In elderly patients, as with this study, cardiac amyloidosis most often results from abnormalities in the liver protein transthyretin (TTR), a thyroxine and retinol-retinol binding complex transporter in blood. Mutated serum TTR results in familial systemic amyloidosis, whereas wild-type TTR results in senile cardiac amyloidosis predominantly seen in elderly males. Scintigraphy, a common non-invasive method used to facilitate early diagnosis of cardiac amyloidosis was the method used in this study. However, the gold standard for definitive diagnosis of cardiac amyloidosis is endomyocardial biopsy (EMB). Besides organ transplant, which is rarely done, therapy for cardiac amyloidosis is mainly aimed at symptomatic and supportive care. Plenty of evidence has shown that the left ventricular ejection fraction (LVEF) in patients with restrictive cardiomyopathy is usually preserved. However, in this study, we review the unique case of an 82-year-old male who was diagnosed with isolated cardiac amyloidosis with severe systolic dysfunction (decreasedLVEF), the methods used to establish the diagnosis, as well as the therapeutic interventions.

    Amyloidoses
    DIAGNOSIS

 are a family of

    inherited or acquired disorders
    GENETICS

 characterized by the

    deposition of insoluble extracellular protein fibrils in various organs and tissues
    MICROSCOPIC

, thereby

    impairing their function
    SYMPTOMS

.

    Amyloidoses
    DIAGNOSIS

 are typically

    misfolded proteins
    MICROSCOPIC

, and on rare occasions, can

    deposit in the myocardium
    MICROSCOPIC

 resulting in an

    infiltrative/restrictive cardiomyopathy
    DIAGNOSIS

.

    Restrictive cardiomyopathy
    DIAGNOSIS

 is an underdiagnosed cause of

    congestive heart failure (CHF)
    DIAGNOSIS

 with

    preserved ejection fraction
    SYMPTOMS

,

    atrial and ventricular arrhythmias
    SYMPTOMS

 along with

    conduction defects
    SYMPTOMS

. In

    elderly
    AGE

 patients, as with this study,

    cardiac amyloidosis
    DIAGNOSIS

 most often results from

    abnormalities in the liver protein transthyretin (TTR
    GENETICS

), a

    thyroxine and retinol-retinol binding complex transporter in blood
    BIOCHEMICAL

.

    Mutated serum TTR
    GENETICS

 results in

    familial systemic amyloidosis
    DIAGNOSIS

, whereas

    wild-type TTR
    GENETICS

 results in

    senile cardiac amyloidosis
    DIAGNOSIS

 predominantly seen in

    elderly
    AGE

    males
    GENDER

.

    Scintigraphy
    PARACLINICAL

, a common non-invasive method used to facilitate early diagnosis of

    cardiac amyloidosis
    DIAGNOSIS

 was the method used in this study. However, the gold standard for definitive diagnosis of

    cardiac amyloidosis
    DIAGNOSIS

 is

    endomyocardial biopsy (EMB)
    PARACLINICAL

. Besides

    organ transplant
    MEDICATION

, which is rarely done, therapy for

    cardiac amyloidosis
    DIAGNOSIS

 is mainly aimed at

    symptomatic and supportive care
    MEDICATION

. Plenty of evidence has shown that the

    left ventricular ejection fraction (LVEF)
    SYMPTOMS

 in patients with

    restrictive cardiomyopathy
    DIAGNOSIS

    is usually preserved
    SYMPTOMS

. However, in this study, we review the unique case of an

    82-year-old
    AGE

    male
    GENDER

 who was diagnosed with

    isolated cardiac amyloidosis
    DIAGNOSIS

 with

    severe systolic dysfunction (decreasedLVEF)
    SYMPTOMS

, the methods used to establish the diagnosis, as well as the therapeutic interventions.

Amyloidoses
Amyloidoses
infiltrative/restrictive cardiomyopathy
Restrictive cardiomyopathy
congestive heart failure (CHF)
cardiac amyloidosis
familial systemic amyloidosis
senile cardiac amyloidosis
cardiac amyloidosis
cardiac amyloidosis
cardiac amyloidosis
restrictive cardiomyopathy
isolated cardiac amyloidosis

organ transplant
symptomatic and supportive care


False-positive bone scintigraphy denoting transthyretin amyloid in elderly hypertrophic cardiomyopathy.

A positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc-HPD) is believed to have high sensitivity (>99%) and specificity (91%) for the diagnosis of transthyretin amyloid cardiomyopathy. We report the case of an 85-year-old man with increased thickness of ventricular walls and a positive bone scintigraphy, who was unexpectedly found to have sarcomeric hypertrophic cardiomyopathy at left ventricular endomyocardial biopsy. Congo Red staining, immunohistochemistry, and transmission electronmicroscopy on six left ventricular samples scored negative for amyloidosis but were suggestive for sarcomeric hypertrophic cardiomyopathy. Genetic study did not show TTR and most commonly involved sarcomeric genes mutations. In hypertrophic cardiomyopathy focal cell necrosis related to demand/supply oxygen mismatch, small vessels disease or inflammation could be responsible of a false-positive bone scintigraphy signal for transthyretin amyloidosis. Because of this, especially in view of a possible specific treatment, endomyocardial biopsy is highly recommended for the correct diagnosis of cardiomyopathies with hypertrophic phenotype.

A

    positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc-HPD)
    PARACLINICAL

 is believed to have high sensitivity (>99%) and specificity (91%) for the diagnosis of

    transthyretin amyloid cardiomyopathy
    DIAGNOSIS

. We report the case of an

    85-year-old
    AGE

    man
    GENDER

 with

    increased thickness of ventricular walls
    SYMPTOMS

 and a

    positive bone scintigraphy
    SYMPTOMS

, who was unexpectedly found to have

    sarcomeric hypertrophic cardiomyopathy
    DIAGNOSIS

 at

    left ventricular endomyocardial biopsy
    PARACLINICAL

.

    Congo Red staining
    PARACLINICAL

,

    immunohistochemistry
    PARACLINICAL

, and

    transmission electronmicroscopy on six left ventricular samples
    PARACLINICAL

    scored negative for amyloidosis
    NEG_FINDINGS

 but were suggestive for

    sarcomeric hypertrophic cardiomyopathy
    DIAGNOSIS

.

    Genetic study did not show TTR and most commonly involved sarcomeric genes mutations
    NEG_FINDINGS

. In

    hypertrophic cardiomyopathy
    DIAGNOSIS

    focal cell necrosis related to demand/supply oxygen mismatch
    SYMPTOMS

,

    small vessels disease
    SYMPTOMS

 or

    inflammation
    SYMPTOMS

 could be responsible of a

    false-positive bone scintigraphy signal
    SYMPTOMS

 for

    transthyretin amyloidosis
    DIAGNOSIS

. Because of this, especially in view of a possible specific treatment,

    endomyocardial biopsy
    PARACLINICAL

 is highly recommended for the correct diagnosis of

    cardiomyopathies
    DIAGNOSIS

 with

    hypertrophic phenotype
    DIAGNOSIS

.

transthyretin amyloid cardiomyopathy
sarcomeric hypertrophic cardiomyopathy
sarcomeric hypertrophic cardiomyopathy
hypertrophic cardiomyopathy
transthyretin amyloidosis
cardiomyopathies
hypertrophic phenotype


Carpal Tunnel Syndrome in Transthyretin Cardiac Amyloidosis: Implications and Protocol for Diagnosis and Treatment.

Amyloidosis is a group of disorders that occurs due to the aggregation of insoluble and misfolded proteins in the extracellular space, eventually resulting in organ dysfunction. Type II amyloidosis is caused by the deposition of transthyretin (TTR), which will be the main focus of this article. Deposition of TTR in the myocardium results in a restrictive form of cardiomyopathy. TTR can also deposit in the flexor tenosynovium resulting in carpal tunnel syndrome (CTS). CTS develops five to ten years prior to cardiac amyloidosis (CA), and therefore, the temporal relationship allows CTS to be a diagnostic indicator for CA. This report discusses a 65-year-old female and a 76-year-old male, both presenting with pain and paresthesia in the distribution of the median nerve in the left and right wrist. In each case, the diagnosis of bilateral CTS was supported by a positive Phalen's maneuver and Tinel's sign. Subsequent tenosynovial and transverse carpal ligament biopsies were performed with Congo red stain revealing amyloid deposits of TTR monomers. This prompted the investigation into possible cardiac involvement. Following cardiac evaluation, the diagnosis of CA was established for the deposition of TTR amyloid monomers. CA has gained much attention in the medical community due to the improvements in cardiac imaging, therapeutic interventions, and diagnostic indicators. Medical professionals should be urged to have a high level of clinical suspicion and refer patients with CTS and select risk factors for cardiac evaluation.

    Amyloidosis
    DIAGNOSIS

 is a group of disorders that occurs due to the

    aggregation of insoluble and misfolded proteins in the extracellular space
    MICROSCOPIC

, eventually resulting in

    organ dysfunction
    SYMPTOMS

.

    Type II amyloidosis
    DIAGNOSIS

 is caused by the

    deposition of transthyretin (TTR)
    MICROSCOPIC

, which will be the main focus of this article.

    Deposition of TTR in the myocardium
    MICROSCOPIC

 results in a

    restrictive form of cardiomyopathy
    DIAGNOSIS

. TTR can also

    deposit in the flexor tenosynovium
    MICROSCOPIC

 resulting in

    carpal tunnel syndrome (CTS)
    DIAGNOSIS

.

    CTS
    DIAGNOSIS

 develops five to ten years prior to

    cardiac amyloidosis (CA)
    DIAGNOSIS

, and therefore, the temporal relationship allows

    CTS
    DIAGNOSIS

 to be a diagnostic indicator for

    CA
    DIAGNOSIS

. This report discusses a

    65-year-old
    AGE

    female
    GENDER

 and a

    76-year-old
    AGE

    male
    GENDER

, both presenting with

    pain and paresthesia in the distribution of the median nerve in the left and right wrist
    SYMPTOMS

. In each case, the diagnosis of

    bilateral CTS
    DIAGNOSIS

 was supported by a

    positive Phalen's maneuver
    SYMPTOMS

 and

    Tinel's sign
    SYMPTOMS

. Subsequent

    tenosynovial and transverse carpal ligament biopsies
    PARACLINICAL

 were performed with

    Congo red stain
    PARACLINICAL

 revealing

    amyloid deposits of TTR monomers
    MICROSCOPIC

. This prompted the investigation into possible

    cardiac involvement
    SYMPTOMS

. Following

    cardiac evaluation
    PARACLINICAL

, the diagnosis of

    CA
    DIAGNOSIS

 was established for the

    deposition of TTR amyloid monomers
    MICROSCOPIC

.

    CA
    DIAGNOSIS

 has gained much attention in the medical community due to the improvements in

    cardiac imaging
    PARACLINICAL

, therapeutic interventions, and diagnostic indicators. Medical professionals should be urged to have a high level of clinical suspicion and refer patients with

    CTS
    DIAGNOSIS

 and select risk factors for

    cardiac evaluation
    PARACLINICAL

.

Amyloidosis
Type II amyloidosis
restrictive form of cardiomyopathy
carpal tunnel syndrome (CTS)
CTS
cardiac amyloidosis (CA)
CTS
CA
bilateral CTS
CA
CA
CTS