Management of a patient with hereditary angioneurotic edema.

Patients with a history of hereditary angioneurotic edema can adequate and safely have nonelective surgical procedures performed with proper preoperative and postoperative management. Deficient amounts of C1 esterase inhibitor can be replaced with fresh frozen plasma; capillary permeability and spreading edema can be prevented with antifibrinolytic agents such as Amicar. Once edema has occurred peripherally and no laryngeal symptoms are present, conservative treatment is advisable. When epiglottic and laryngeal edema occurs, intubation or tracheostomy is preferred for maintenance of airway until the edema subsides. During oral surgical procedures, minimal surgical trauma must be achieved. Edema that involves the airway presents the greatest danger to patients. These attacks are usually associated with dental or some sort of oral or pharyngeal manipulation.

Patients with a history of

    hereditary angioneurotic edema
    DIAGNOSIS

 can adequate and safely have

    nonelective surgical procedures
    MEDICATION

 performed with proper

    preoperative and postoperative management
    MEDICATION

.

    Deficient amounts of C1 esterase inhibitor
    BIOCHEMICAL

 can be

    replaced with fresh frozen plasma
    MEDICATION

;

    capillary permeability
    BIOCHEMICAL

 and

    spreading edema
    SYMPTOMS

 can be prevented with

    antifibrinolytic agents such as Amicar
    MEDICATION

. Once

    edema has occurred peripherally
    SYMPTOMS

 and

    no laryngeal symptoms are present
    NEG_FINDINGS

,

    conservative treatment
    MEDICATION

 is advisable. When

    epiglottic and laryngeal edema
    SYMPTOMS

 occurs,

    intubation or tracheostomy
    MEDICATION

 is preferred for

    maintenance of airway
    MEDICATION

 until the

    edema subsides
    SYMPTOMS

. During

    oral surgical procedures
    MEDICATION

,

    minimal surgical trauma
    MEDICATION

 must be achieved.

    Edema that involves the airway
    SYMPTOMS

 presents the greatest danger to patients. These attacks are usually associated with

    dental or some sort of oral or pharyngeal manipulation
    MEDICATION

.

spreading edema
edema has occurred peripherally
epiglottic and laryngeal edema
edema subsides
Edema that involves the airway


Acquired angioedema associated with rectal carcinoma and its response to danazol therapy. Acquired angioedema treated with danazol.

Cases of the acquired form of angioedema have been recognized as a separate entity since 1972. Previously reported cases have been related to various hematologic malignancies. We have recently studied a patient with rectal carcinoma who manifests a complement pattern compatible with the acquired form of angioedema. No previous personal or family history of allergic disease or angioedema was present. Because the episodes of angioedema were laryngeal in location and required emergency intubation to maintain an adequate airway, a trial of danazol prophylaxis, which has been shown to be effective in hereditary angioedema, was undertaken. His beneficial response to this form of therapy is also documented.

Cases of the

    acquired form of angioedema
    DIAGNOSIS

 have been recognized as a separate entity since 1972. Previously reported cases have been related to various

    hematologic malignancies
    DIAGNOSIS

. We have recently studied a patient with

    rectal carcinoma
    DIAGNOSIS

 who manifests a

    complement pattern compatible with the acquired form of angioedema
    SYMPTOMS

.

    No previous personal or family history of allergic disease or angioedema was present
    NEG_FINDINGS

. Because the

    episodes of angioedema were laryngeal in location
    SYMPTOMS

 and required

    emergency intubation to maintain an adequate airway
    MEDICATION

, a

    trial of danazol prophylaxis
    MEDICATION

, which has been shown to be effective in

    hereditary angioedema
    DIAGNOSIS

, was undertaken.

    His
    GENDER

 beneficial response to this

    form of therapy
    MEDICATION

 is also documented.

acquired form of angioedema
hematologic malignancies
rectal carcinoma
hereditary angioedema


[HLA and erythrocyte genetic markers in a family with hereditary angioneurotic edema (author's transl)].

The study deals with a family of 22 members spreading over four generations; 14 members suffer from hereditary angio-neurotic edema; all of them have been typed for 30 antigens of the A and B loci in the HLA System and for ABO and Rhesus erythrocyte markers. There is no connection between the disease and any of the markers considered. As for the HLA system, there should be at least 7 chromosomic recombinants to account for the relationship with one of the haplotypes involved.

The study deals with a family of 22 members spreading over four generations; 14 members suffer from

    hereditary angio-neurotic edema
    SYMPTOMS

; all of them have been typed for

    30 antigens of the A and B loci in the HLA System
    GENETICS

 and for

    ABO and Rhesus erythrocyte markers
    GENETICS

. There is

    no connection between the disease and any of the markers
    NEG_FINDINGS

 considered. As for the

    HLA system
    GENETICS

, there should be at least

    7 chromosomic recombinants
    GENETICS

 to account for the relationship

    with one of the haplotypes involved
    GENETICS

.


Hereditary angioedema: review of literature and dental treatment.

Hereditary angioedema (HAE) is an autosomal dominant syndrome in which the pathogenesis differs from the more common nonhereditary (allergic) angioedema. Respiratory embarrassment precipitated by trauma (including dental manipulation) accounts for the high morbidity of the patients. The purpose of this paper is to establish a successful procedure for dental-medical treatment of patients with HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant syndrome
    GENETICS

 in which the pathogenesis differs from the more common

    nonhereditary (allergic) angioedema
    DIAGNOSIS

.

    Respiratory embarrassment precipitated by trauma (including dental manipulation
    SYMPTOMS

) accounts for the high morbidity of the patients. The purpose of this paper is to establish a successful procedure for

    dental-medical treatment
    MEDICATION

 of patients with

    HAE
    DIAGNOSIS

.

Hereditary angioedema (HAE)
nonhereditary (allergic) angioedema
HAE


Hereditary angio-oedema with mesangiocapillary glomerulonephritis.

A patient with hereditary angio-oedema (HAO) developed mesangiocapillary glomerulonephritis (MCGN) under observation. HAO is characterized by an inherited defect of complement-deficiency of C1 esterase. MCGN is often associated with another complement abnormality which leads to depression of serum C3 and there is some evidence that the complement abnormality precedes the nephritis. The coincidence of these two rare diseases in the present patient, and in one previously described, suggests that other complement abnormalities may predispose to the development of MCGN.

A patient with

    hereditary angio-oedema (HAO)
    DIAGNOSIS

 developed

    mesangiocapillary glomerulonephritis (MCGN)
    DIAGNOSIS

 under observation.

    HAO
    DIAGNOSIS

 is characterized by an

    inherited defect of complement-deficiency of C1 esterase
    GENETICS

.

    MCGN
    DIAGNOSIS

 is often associated with another

    complement abnormality
    BIOCHEMICAL

 which leads to

    depression of serum C3
    BIOCHEMICAL

 and there is some evidence that the

    complement abnormality
    BIOCHEMICAL

 precedes the

    nephritis
    DIAGNOSIS

. The coincidence of these two rare diseases in the present patient, and in one previously described, suggests that other

    complement abnormalities
    BIOCHEMICAL

 may predispose to the development of

    MCGN
    DIAGNOSIS

.

complement abnormality
depression of serum C3
complement abnormality
complement abnormalities


The anesthetic and perioperative management of a patient with documented hereditary angioneurotic edema.

A patient with documented hereditary angioneurotic edema was admitted for elective surgical extraction of 3 impacted 3rd molars under local anesthesia. In order to increase his C'1-INH level, he was prepared for operation with 2 units of fresh-frozen plasma 24 hours preoperatively. Postoperatively, he was observed in the ICU for 24 hours and on the ward for 2 days, and was discharged without any complications from the surgical trauma.

A patient with documented

    hereditary angioneurotic edema
    SYMPTOMS

 was admitted for

    elective surgical extraction of 3 impacted 3rd molars
    MEDICATION

 under

    local anesthesia
    MEDICATION

. In order to

    increase
    BIOCHEMICAL

 his

    C'1-INH level
    BIOCHEMICAL

,

    he
    GENDER

 was

    prepared for operation with 2 units of fresh-frozen plasma 24 hours preoperatively
    MEDICATION

.

    Postoperatively
    MEDICATION

,

    he
    GENDER

 was

    observed in the ICU for 24 hours and on the ward for 2 days
    MEDICATION

, and was discharged

    without any complications from the surgical trauma
    NEG_FINDINGS

.


Hereditary angio-oedema.

A family with three affected but only two symptomatic members with angio-oedema is described. One had potentially life threatening dental treatment at presentation while the other had inexplicable gastro-intestinal disease.

A

    family with three affected but only two symptomatic members with angio-oedema
    FAMILY

 is described. One had

    potentially life threatening dental treatment
    MEDICATION

 at presentation while the other had

    inexplicable gastro-intestinal disease
    DIAGNOSIS

.


[Abdominal manifestations in hereditary acute angioneurotic oedema. Value of study of the complement system (author's transl)].

Four individuals of the same family suffered from a functional deficiency in C1 esterase inhibitor. In three of them, the manifestations of hereditary angioneurotic oedema were abdominal, paroxystic and pseudo-surgical. They were related to the development of visceral or mucosal oedema. The measurement of total complement (and of its fractions) during the acute episode, as well as dynamic complement studies between attacks, represent a simple method for indicating the probable diagnosis. Only estimation of the functional activity of C1 esterase inhibitor provides definite evidence. Familiarity with the clinical and biological characteristics of these acute abdominal episodes makes it possible to avoid repeated, unnecessary operations in these patients. They should be treated medically, under surgical surveillance, since a patient with angioneurotic oedema may have nevertheless a specific lesion, in addition. In addition, the episode may spread at any time, resulting in oedema of the glottis requiring tracheotomy or immediate intubation.

Four individuals of the same family suffered from a

    functional deficiency in C1 esterase inhibitor
    BIOCHEMICAL

. In three of them, the manifestations of

    hereditary angioneurotic oedema
    SYMPTOMS

 were

    abdominal
    SYMPTOMS

    , paroxystic and pseudo-surgical
    SYMPTOMS

. They were related to the development of

    visceral or mucosal oedema
    SYMPTOMS

. The

    measurement of total complement (and of its fractions)
    PARACLINICAL

 during the acute episode, as well as

    dynamic complement studies
    PARACLINICAL

 between attacks, represent a simple method for indicating the probable diagnosis. Only estimation of the

    functional activity of C1 esterase inhibitor
    BIOCHEMICAL

 provides definite evidence. Familiarity with the clinical and biological characteristics of these

    acute abdominal episodes
    SYMPTOMS

 makes it possible to avoid

    repeated, unnecessary operations
    NEG_FINDINGS

 in these patients. They should be treated medically, under

    surgical surveillance
    MEDICATION

, since a patient with

    angioneurotic oedema
    SYMPTOMS

 may have nevertheless a specific lesion, in addition. In addition, the episode may spread at any time, resulting in

    oedema of the glottis
    SYMPTOMS

 requiring

    tracheotomy
    MEDICATION

 or

    immediate intubation
    MEDICATION

.

hereditary angioneurotic oedema
abdominal
, paroxystic and pseudo-surgical
visceral or mucosal oedema
acute abdominal episodes
angioneurotic oedema
oedema of the glottis

surgical surveillance
tracheotomy
immediate intubation


Diagnostic and therapeutic problems associated with hereditary deficiency of the C1 esterase inhibitor.

Six patients in a family with a history of hereditary angioedema reported swelling of the extremities and recurrent abdominal pain occurring spontaneously or after trauma. Attacks of oedema involving the airways, the greatest danger with this disorder, were present only in one case. This autosomal dominant disease is due to deficient activity of the inhibitor of the first component of complement. Low levels of C4, and absence of C1 esterase inhibitor confirm the diagnosis. Two asymptomatic cases with the appropriate biochemical abnormality are reported in this study. For short term prophylaxis of attacks (before surgery expecially), fresh frozen plasma is used, or better still, C1 esterase inhibitor. For long term prophylaxis of attacks antifibrinolytic and hormonal drugs are used: in two cases, the authors obtained good results with methyltestosterone after failure of tranexamic acid.

Six patients in a

    family with a history of hereditary angioedema
    FAMILY

 reported

    swelling of the extremities
    SYMPTOMS

 and

    recurrent abdominal pain
    SYMPTOMS

 occurring

    spontaneously or after trauma
    SYMPTOMS

.

    Attacks of oedema involving the airways
    SYMPTOMS

, the greatest danger with this disorder, were present only in one case. This

    autosomal dominant disease
    GENETICS

 is due to

    deficient activity of the inhibitor of the first component of complement
    BIOCHEMICAL

.

    Low levels of C4,
    BIOCHEMICAL

 and

    absence of C1 esterase inhibitor
    BIOCHEMICAL

 confirm the diagnosis. Two asymptomatic cases with the appropriate biochemical abnormality are reported in this study. For

    short term prophylaxis of attacks (before surgery
    MEDICATION

 expecially),

    fresh frozen plasma
    MEDICATION

 is used, or better still,

    C1 esterase inhibitor
    MEDICATION

. For

    long term prophylaxis of
    MEDICATION

 attacks

    antifibrinolytic and hormonal drugs
    MEDICATION

 are used: in two cases, the authors obtained good results with

    methyltestosterone
    MEDICATION

 after

    failure of tranexamic acid
    NEG_FINDINGS

.

swelling of the extremities
recurrent abdominal pain
spontaneously or after trauma
Attacks of oedema involving the airways


Laryngeal oedema due to hereditary angioedema.

A case is reported in which a young man suffering from hereditary angioedema was admitted with severe airway obstruction due to groww pharyngeal and laryngeal oedema. Tracheostomy was necessary. The rationale of treatment with epsilon aminocaproic acid, tranexamic acid and fresh frozen plasma is discussed. The patient subsequently underwent dental extractions under general anaesthesia with tracheal intubation without complications.

A case is reported in which a

    young
    AGE

    man
    GENDER

 suffering from

    hereditary angioedema
    DIAGNOSIS

 was admitted with

    severe airway obstruction
    SYMPTOMS

 due to

    groww pharyngeal and laryngeal oedema
    SYMPTOMS

.

    Tracheostomy
    MEDICATION

 was necessary. The rationale of

    treatment with epsilon aminocaproic acid, tranexamic acid and fresh frozen plasma
    MEDICATION

 is discussed. The patient subsequently underwent

    dental extractions under general anaesthesia with tracheal intubation
    MEDICATION

    without complications
    NEG_FINDINGS

.

severe airway obstruction
groww pharyngeal and laryngeal oedema


Hereditary complement defect and kinins involvement in asthma.

Relationship between an inherited qualitative defect of the complement system and intrinsic asthma, and the direct participation of the kinin system in producing asthma, are reported. Qualitative complement impairment that produced hereditary angioedema in the son of an asthmatic father indicated that the kinin system was the vasoactive mediator in both cases.

Relationship between an

    inherited qualitative defect of the complement system
    GENETICS

 and

    intrinsic asthma
    DIAGNOSIS

, and the direct participation of the

    kinin system
    BIOCHEMICAL

 in producing asthma, are reported.

    Qualitative complement impairment
    BIOCHEMICAL

 that produced

    hereditary angioedema in the son of an asthmatic father
    FAMILY

 indicated that the

    kinin system
    BIOCHEMICAL

 was the

    vasoactive mediator
    BIOCHEMICAL

 in both cases.

kinin system
Qualitative complement impairment
kinin system
vasoactive mediator


[Abdominal manifestations of hereditary angioneurotic edema. Importance of the exploration of the complement system (apropos of 29 families)].

Abdominal manifestations are almost constantly present (85% of cases) in the current form of hereditary Quincke's disease. In some cases, these abdominal manifestations occur even when cutaneomucosal edema is not present which leads to unwarranted often repeated and sometimes dangerous surgery. Apart from a story of heredity diagnosis of such troubles is possible, provided the total complement has been assayed to note its sharp fall. It can be subsequently explained by a functional defect of the C1 esterase inhibitor or alpha2-neuraminoglycoprotein.

    Abdominal manifestations
    SYMPTOMS

 are almost constantly present (85% of cases) in the current form of

    hereditary Quincke's disease
    DIAGNOSIS

. In some cases, these

    abdominal manifestations
    SYMPTOMS

 occur even when

    cutaneomucosal edema is not present
    NEG_FINDINGS

 which leads to

    unwarranted
    NEG_FINDINGS

 often repeated and sometimes dangerous

    surgery
    MEDICATION

. Apart from a story of heredity diagnosis of such

    troubles
    SYMPTOMS

 is possible, provided the

    total complement has been assayed
    BIOCHEMICAL

 to note

    its sharp fall
    BIOCHEMICAL

. It can be subsequently explained by a

    functional defect of the C1 esterase inhibitor or alpha2-neuraminoglycoprotein
    BIOCHEMICAL

.

Abdominal manifestations
abdominal manifestations
troubles

cutaneomucosal edema is not present
unwarranted


Familial anglo-oedema--a particularly severe form.

A case of hereditary angio-oedema is described together with the family history and manifestations in the father of the patient. The problems encountered in his management are discussed, including tracheostomy and genetic counselling.

A case of

    hereditary angio-oedema
    DIAGNOSIS

 is described together with the

    family history and manifestations in the father of the patient
    FAMILY

. The problems encountered in his management are discussed, including

    tracheostomy
    MEDICATION

 and

    genetic counselling
    MEDICATION

.


Evidence for immune complexes involving anti-lymphocyte antibodies associated with hypocomplementaemia in chronic lymphocytic leukaemia (CLL).

Unmeasurable total haemolytic complement (C) was observed in serum of a patient with untreated chronic lymphocytic leukaemia and recurrent non-hereditary angioedema. Analysis of C components immunochemically demonstrated a marked reduction of C1q and C1s inhibitor, undetectable C1r, C1s and an elevated B. Haemolytic C1, C4 and C2 were less than 5 percent of normal, functional C1s inhibitor was absent. Cryoglobulin and C1q precipitins were present in the serum. Of special interest was the presence of high levels of cold-reactive antilymphocyte antibody, determined by both C-dependent cytotoxicity and indirect immunofluorescence. The antibody exhibited specificities for both autologous lymphocytes and lymphocytes from normal donors; cytotoxic activity for autologous leukaemia cells was removed by absorption with normal isologous tonsil lymphocytes. Specific enrichment of this antibody relative to the serum level was demonstrated in the cryoglobulin and its isolated 19S fractions. Free lymphocyte surface antigen was also demonstrated by gel diffusion using specific rabbit antilymphocyte antiserum. These data strongly suggest the presence of pathogenetically significant circulating complexes of lymphocyte surface antigen and specific antibody in certain patients with CLL.

    Unmeasurable total haemolytic complement (C) was observed in serum
    BIOCHEMICAL

 of a patient with

    untreated chronic lymphocytic leukaemia
    DIAGNOSIS

 and

    recurrent non-hereditary angioedema
    NEG_FINDINGS

.

    Analysis of C components
    PARACLINICAL

    immunochemically
    PARACLINICAL

 demonstrated a

    marked reduction of C1q and C1s inhibitor
    BIOCHEMICAL

,

    undetectable C1r, C1s and an elevated B. Haemolytic C1, C4 and C2 were less than 5 percent of normal
    BIOCHEMICAL

,

    functional C1s inhibitor was absent
    BIOCHEMICAL

.

    Cryoglobulin and C1q precipitins were present in the serum
    BIOCHEMICAL

. Of special interest was the presence of

    high levels of cold-reactive antilymphocyte antibody
    BIOCHEMICAL

, determined by both

    C-dependent cytotoxicity
    BIOCHEMICAL

 and

    indirect immunofluorescence
    PARACLINICAL

. The

    antibody exhibited specificities for both
    BIOCHEMICAL

 autologous lymphocytes and lymphocytes from normal donors;

    cytotoxic activity for autologous leukaemia cells was removed by absorption with normal isologous tonsil lymphocytes
    NEG_FINDINGS

.

    Specific enrichment of this antibody relative to the serum level
    BIOCHEMICAL

 was demonstrated

    in the cryoglobulin and its isolated 19S fractions
    BIOCHEMICAL

.

    Free lymphocyte surface antigen
    MICROSCOPIC

 was also demonstrated by gel diffusion using specific

    rabbit antilymphocyte antiserum
    BIOCHEMICAL

. These data strongly suggest the presence of pathogenetically significant

    circulating complexes of lymphocyte surface antigen and specific antibody
    MICROSCOPIC

 in certain patients with

    CLL
    DIAGNOSIS

.

untreated chronic lymphocytic leukaemia
CLL


Acquired angioedema with lymphoproliferative disorder: association of C1 inhibitor deficiency with cellular abnormality.

A patient with a lymphoproliferative disorder, angioedema, and an acquired deficiency of the inhibitor of the activated first component of complement was studied. The patient's complement profile revealed depletion of the first component of complement, which has not been seen in angioedema of the hereditary type. There was no evidence for C1-depleting activity in the patient's plasma. The majority of the patient's peripheral blood mononuclear cells resembled B cells in their memebrane receptor properties and in that they carried easily detectable immunoglobulin, predominantly IgM. However, these cells were unusual in that they phagocytosed both latex particles and C3-coated erythrocytes. Morphological study of the cells infiltrating the patient's lung revealed immature, atypical, and plasmacytoid lymphocytes and immunoblasts. Both the patient's peripheral blood mononuclear cells and a suspension of cells from the pulmonary infiltrate were capable of depleting the first component of complement and its inhibitor from homologous plasma. Normal ABO-compatible cells did not possess this property. The data suggested that the patient's abnormal lymphoid cells may have interacted with the complement system to produce a biochemical defect and a clinical syndrome closely resembling angioedema of the hereditary type.

A patient with a

    lymphoproliferative disorder
    DIAGNOSIS

,

    angioedema
    DIAGNOSIS

, and an

    acquired deficiency of the inhibitor of the activated first component of complement
    BIOCHEMICAL

 was studied. The patient's

    complement profile
    BIOCHEMICAL

 revealed

    depletion of the first component of complement
    BIOCHEMICAL

, which has not been seen in

    angioedema of the hereditary type
    DIAGNOSIS

. There was

    no evidence for C1-depleting activity in the patient's plasma
    NEG_FINDINGS

. The

    majority of the patient's peripheral blood mononuclear cells resembled B cells in their memebrane receptor properties
    MICROSCOPIC

 and in that they carried easily detectable immunoglobulin, predominantly IgM. However, these cells were unusual in that they

    phagocytosed both latex particles and C3-coated erythrocytes
    MICROSCOPIC

.

    Morphological study of the cells infiltrating the patient's lung
    PARACLINICAL

 revealed

    immature, atypical, and plasmacytoid lymphocytes and immunoblasts
    MICROSCOPIC

.

    Both the patient's peripheral blood mononuclear cells and a suspension of cells from the pulmonary infiltrate
    MICROSCOPIC

    were capable of depleting the first component of complement and its inhibitor from homologous plasma
    BIOCHEMICAL

.

    Normal ABO-compatible cells did not possess this
    NEG_FINDINGS

 property. The data suggested that the patient's

    abnormal lymphoid cells
    MICROSCOPIC

 may have interacted with the complement system to produce a biochemical defect and a clinical syndrome closely resembling

    angioedema of the hereditary type
    DIAGNOSIS

.

lymphoproliferative disorder
angioedema
angioedema of the hereditary type
angioedema of the hereditary type


Acute angioneurotic edema of the lips and tongue due to emotional stress.

Angioneurotic edema, though a fairly common medical condition, is rarely seen in dental practice. As laryngeal involvement can occur spontaneously and suddenly in the dental office or a similar complication can develop abruptly after administration of certain drugs used in dentistry, an understanding of this condition is definitely indicated. Moreover, as the hereditary form of this clinical entity can be precipitated by trauma, such as various dental and oral surgical procedures with a high incidence of laryngeal edema, an awareness of this phenomenon is an absolute necessity for sound medical and dental practice.

    Angioneurotic edema
    SYMPTOMS

, though a fairly common medical condition, is rarely seen in dental practice. As

    laryngeal involvement
    SYMPTOMS

 can occur spontaneously and suddenly in the dental office or a similar complication can develop abruptly after administration of certain drugs used in dentistry, an understanding of this condition is definitely indicated. Moreover, as the hereditary form of this clinical entity can be precipitated by

    trauma
    SYMPTOMS

, such as various dental and

    oral surgical procedures
    MEDICATION

 with a high incidence of

    laryngeal edema
    SYMPTOMS

, an awareness of this phenomenon is an absolute necessity for sound medical and dental practice.

Angioneurotic edema
laryngeal involvement
trauma
laryngeal edema


Hereditary angioneurotic edema treated by partial uvulectomy.

Hereditary angioneurotic edema (HANE) is a rare familial disease of C1 esterase inhibitor deficiency that produces recurring attacks of acute, circumscribed, noninflammatory edema. The technique of partial uvulectomy to treat HANE can reduce the mortality from this condition due to asphyxiation. Three cases in which partial uvulectomy was the successful mode of treatment are described.

    Hereditary angioneurotic edema (HANE)
    DIAGNOSIS

 is a

    rare familial disease
    GENETICS

 of

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

 that produces

    recurring attacks of acute, circumscribed, noninflammatory edema
    SYMPTOMS

. The technique of

    partial uvulectomy
    MEDICATION

 to treat

    HANE
    DIAGNOSIS

 can reduce the mortality from this condition due to

    asphyxiation
    SYMPTOMS

. Three cases in which

    partial uvulectomy
    MEDICATION

 was the successful mode of treatment are described.

Hereditary angioneurotic edema (HANE)
HANE


[Angioneurotic hereditary edema. 3 faimilial cases].

The study involved three families with hane. This disorder differs from the simple condition by its preferential visceral localisation (digestive and, above all, the glottis), its hereditary nature and the existence of a biological abnormality affecting the serum complement system (absence of enzyme activity of C1 esterase inhibitor in the serum of sufferers). The cases reported illustrate the serious prognosis of this condition (four deaths by asphyxia in one family) in the absence of specific therapy. This disorder, although rare, represents a fundamental problem in general pathology by virtue of the enzymatic, immunological and genetic processes which it involves.

The study involved three families with

    hane
    DIAGNOSIS

. This disorder differs from the simple condition by its

    preferential visceral localisation (digestive and
    SYMPTOMS

, above all,

    the glottis)
    SYMPTOMS

, its

    hereditary nature
    GENETICS

 and the existence of a

    biological abnormality affecting the serum complement system
    BIOCHEMICAL

 (

    absence of enzyme activity of C1 esterase inhibitor in the serum of sufferers)
    BIOCHEMICAL

. The cases reported illustrate the serious prognosis of this condition (four

    deaths by asphyxia
    SYMPTOMS

 in one family) in the

    absence of specific therapy
    NEG_FINDINGS

. This disorder, although rare, represents a fundamental problem in general pathology by virtue of the enzymatic, immunological and genetic processes which it involves.


[Hereditary non-allergic angioneurotic edema and the complement system (author's transl)].

By way of example of a patient and his family and by means of the literature, the present knowledge of pathogenesis and therapy of hereditary non-allergic angioneurotic edema has been reviewed.

By way of example of a patient and his family and by means of the literature, the present knowledge of pathogenesis and therapy of

    hereditary non-allergic angioneurotic edema
    DIAGNOSIS

 has been reviewed.


Treatment of hereditary angioneurotic edema with tranexamic acid and cinnarizine.

Six out of 7 Finnish patients suffering from hereditary angioneurotic edema were helped during attacks, by treatment with tranexamic acid (AMCA, Cyklokapron, Kabi) in doses of 1.5 g 3 times daily, follow-up time 3-25 months. 3 of these patients also had continuous AMCA treatment, in the course of which 2 remained nearly symptom-free on a dosage of 1 g 2-3 times daily. Even the third one had shorter and milder attacks. One patient, however, had to stop taking AMCA after 6 weeks' treatment, because of fatigue and nausea. Follow-up time for the others was 9-11 months. For comparative purposes, 3 patients were given continuous treatment with an antihistamine, cinnarizine in a dosage of 20-30 mg daily. Two of the patients were helped by it, one becoming nearly symptom-free and the other having fewer and milder attacks; follow-up time 9-10 months.

Six out of 7

    Finnish
    ETHNICITY

 patients suffering from

    hereditary angioneurotic edema
    DIAGNOSIS

 were helped during attacks, by

    treatment with tranexamic acid (AMCA, Cyklokapron, Kabi) in doses of 1.5 g 3 times daily
    MEDICATION

, follow-up time 3-25 months. 3 of these patients also had

    continuous AMCA treatment
    MEDICATION

, in the course of which 2 remained

    nearly symptom-free
    SYMPTOMS

    on a dosage of 1 g 2-3 times daily
    MEDICATION

. Even the third one had

    shorter and milder attacks
    SYMPTOMS

. One patient, however, had to

    stop taking AMCA after 6 weeks' treatment
    MEDICATION

, because of

    fatigue
    SYMPTOMS

 and

    nausea
    SYMPTOMS

. Follow-up time for the others was 9-11 months. For comparative purposes, 3 patients were given

    continuous treatment with an antihistamine, cinnarizine in a dosage of 20-30 mg daily
    MEDICATION

. Two of the patients were helped by it, one becoming

    nearly symptom-free
    SYMPTOMS

 and the other having

    fewer and milder attacks
    SYMPTOMS

; follow-up time 9-10 months.

nearly symptom-free
shorter and milder attacks
fatigue
nausea
nearly symptom-free
fewer and milder attacks


Adrenalin treatment for hereditary angioneurotic edema.

In two patients studied with HAE the repeated use of 1.0 cc of 1:1000 epinephrine every hour for episodes threatening the upper airway resulted in both subjective and objective improvement of signs and symptoms in a manner we interpret as helpful. No harmful side effects have been encountered in these two young, otherwise healthy, people. Until a more definite therapy is found, we believe repeated high doses of adrenalin should be considered in young patients with HAE presenting with symptoms and signs of airway involvement.

In two patients studied with

    HAE
    DIAGNOSIS

 the

    repeated use of 1.0 cc of 1:1000 epinephrine every hour for episodes threatening the upper airway
    MEDICATION

 resulted in

    both subjective and objective improvement of signs and symptoms
    SYMPTOMS

 in a manner we interpret as helpful.

    No harmful side effects
    NEG_FINDINGS

 have been encountered in these two

    young
    AGE

, otherwise healthy, people. Until a more definite therapy is found, we believe

    repeated high doses of adrenalin
    MEDICATION

 should be considered in

    young
    AGE

 patients with

    HAE
    DIAGNOSIS

 presenting with

    symptoms and signs of airway involvement
    SYMPTOMS

.


Hereditary angioedema with 14-year remission.

The concept that hereditary angioedema assumes a benign form in some families is supported by documented disease in a 37-year-old man who had had recurrent attacks for one year but has been without symptoms for 14 years. Although numerous members of the patient's family have been affected during the past five generations, known causes of death have not been directly related to angioedema.

The concept that

    hereditary angioedema
    DIAGNOSIS

 assumes a benign form in some families is supported by documented disease in a

    37-year-old
    AGE

    man
    GENDER

 who had had

    recurrent attacks for one year
    SYMPTOMS

 but

    has been without symptoms for 14 years
    NEG_FINDINGS

. Although

    numerous members of the patient's family have been affected during the past five generations
    FAMILY

, known causes of

    death
    SYMPTOMS

 have not been directly related to

    angioedema
    DIAGNOSIS

.


Late-Onset Dystrophinopathy.

Dystrophinopathy is a spectrum of muscular dystrophies resulting from absolute to relative deficiency of dystrophin - a protein essential for muscle fiber integrity. This includes a severe form called Duchenne muscular dystrophy, a mild form called Becker muscular dystrophy, and intermediate muscular dystrophy. Becker muscular dystrophy relates to late-onset and slow progression muscle dystrophy caused by deletions or duplications in the dystrophin gene. Individuals with this type of tardive slow progression have a life expectancy of 60 years. A patient in his late 40s presented this disease with duplication of exon 2 in the dystrophin gene.

    Dystrophinopathy
    DIAGNOSIS

 is a spectrum of

    muscular dystrophies
    DIAGNOSIS

 resulting from

    absolute to relative deficiency of dystrophin -
    BIOCHEMICAL

 a protein essential for

    muscle fiber integrity
    SYMPTOMS

. This includes a severe form called

    Duchenne muscular dystrophy
    DIAGNOSIS

, a mild form called

    Becker muscular dystrophy
    DIAGNOSIS

, and

    intermediate muscular dystrophy
    DIAGNOSIS

.

    Becker muscular dystrophy
    DIAGNOSIS

 relates to

    late-onset and slow progression muscle dystrophy
    DIAGNOSIS

 caused by

    deletions or duplications in the dystrophin gene
    GENETICS

. Individuals with this type of

    tardive slow progression
    SYMPTOMS

 have a

    life expectancy of 60 years
    AGE

. A patient in

    his
    GENDER

    late 40s
    AGE

 presented this disease with

    duplication of exon 2 in the dystrophin gene
    GENETICS

.

muscle fiber integrity
tardive slow progression


Early treatment with Ataluren of a 2-year-old boy with nonsense mutation Duchenne dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked myopathy caused by mutations, in most cases deletions and duplications, in the dystrophin gene. Point mutations account for 13% and stop codon mutations are even rarer. Ataluren was approved for the treatment of DMD caused by nonsense mutations in 2014, and several clinical trials documented its efficacy and safety. However, few real-life experience data is available, especially in pediatric age. We report the case of a 2-year- ambulant child affected by DMD caused by the stop-codon mutation c.10801C > T, p.Gln3601X in exon 76, who was early treated with Ataluren at a dosage of 40 mg/kg/die, and presented a rapid improvement in both muscle strength and cognitive and social skills.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    myopathy
    DIAGNOSIS

 caused by

    mutations,
    GENETICS

 in most cases

    deletions and duplications, in the dystrophin gene
    GENETICS

.

    Point mutations
    GENETICS

 account for 13% and

    stop codon mutations
    GENETICS

 are even rarer.

    Ataluren
    MEDICATION

 was approved for the treatment of

    DMD
    DIAGNOSIS

 caused by

    nonsense mutations
    GENETICS

 in 2014, and several clinical trials documented its efficacy and safety. However, few real-life experience data is available, especially in

    pediatric
    AGE

    age
    AGE

. We report the case of a

    2-year- ambulant
    AGE

    child
    AGE

 affected by

    DMD
    DIAGNOSIS

 caused by the

    stop-codon mutation c.10801C > T, p.Gln3601X in exon 76
    GENETICS

, who was

    early treated with Ataluren at a dosage of 40 mg/kg/die
    MEDICATION

, and presented a

    rapid improvement in both muscle strength and cognitive and social skills
    SYMPTOMS

.

Duchenne muscular dystrophy (DMD)
myopathy
DMD
DMD


Integrating Whole-Genome Sequencing in Clinical Genetics: A Novel Disruptive Structural Rearrangement Identified in the Dystrophin Gene (DMD).

While in most patients the identification of genetic alterations causing dystrophinopathies is a relatively straightforward task, a significant number require genomic and transcriptomic approaches that go beyond a routine diagnostic set-up. In this work, we present a Becker Muscular Dystrophy patient with elevated creatinine kinase levels, progressive muscle weakness, mild intellectual disability and a muscle biopsy showing dystrophic features and irregular dystrophin labelling. Routine molecular techniques (Southern-blot analysis, multiplex PCR, MLPA and genomic DNA sequencing) failed to detect a defect in the DMD gene. Muscle DMD transcript analysis (RT-PCR and cDNA-MLPA) showed the absence of exons 75 to 79, seen to be present at the genomic level. These results prompted the application of low-coverage linked-read whole-genome sequencing (WGS), revealing a possible rearrangement involving DMD intron 74 and a region located upstream of the PRDX4 gene. Breakpoint PCR and Sanger sequencing confirmed the presence of a ~8 Mb genomic inversion. Aberrant DMD transcripts were subsequently identified, some of which contained segments from the region upstream of PRDX4. Besides expanding the mutational spectrum of the disorder, this study reinforces the importance of transcript analysis in the diagnosis of dystrophinopathies and shows how WGS has a legitimate role in clinical laboratory genetics.

While in most patients the identification of

    genetic alterations
    GENETICS

 causing

    dystrophinopathies
    DIAGNOSIS

 is a relatively straightforward task, a significant number require genomic and transcriptomic approaches that go beyond a routine diagnostic set-up. In this work, we present a

    Becker Muscular Dystrophy
    DIAGNOSIS

 patient with

    elevated creatinine kinase levels
    BIOCHEMICAL

,

    progressive muscle weakness
    SYMPTOMS

,

    mild intellectual disability
    SYMPTOMS

 and a

    muscle biopsy
    PARACLINICAL

 showing

    dystrophic features
    SYMPTOMS

 and

    irregular dystrophin labelling
    MICROSCOPIC

.

    Routine molecular techniques (Southern-blot analysis
    NEG_FINDINGS

,

    multiplex PCR, MLPA and genomic DNA sequencing
    PARACLINICAL

)

    failed to detect a defect in the DMD gene
    NEG_FINDINGS

.

    Muscle DMD transcript analysis (RT-PCR and cDNA-MLPA)
    PARACLINICAL

 showed the

    absence of exons 75 to 79, seen to be present at the genomic level
    GENETICS

. These results prompted the application of

    low-coverage linked-read whole-genome sequencing (WGS)
    PARACLINICAL

, revealing a

    possible rearrangement involving DMD intron 74 and a region located upstream of the PRDX4 gene
    GENETICS

.

    Breakpoint PCR and Sanger sequencing
    PARACLINICAL

 confirmed the

    presence of a ~8 Mb genomic inversion
    GENETICS

.

    Aberrant DMD transcripts
    GENETICS

 were subsequently identified,

    some of which contained segments from the region upstream of PRDX4
    GENETICS

. Besides expanding the mutational spectrum of the disorder, this study reinforces the importance of

    transcript analysis
    PARACLINICAL

 in the diagnosis of

    dystrophinopathies
    DIAGNOSIS

 and shows how WGS has a legitimate role in

    clinical laboratory genetics
    PARACLINICAL

.

dystrophinopathies
Becker Muscular Dystrophy
dystrophinopathies

progressive muscle weakness
mild intellectual disability
dystrophic features


Successful Surgical Management of a Tracheo-Innominate Artery Fistula in a Patient with Duchenne Muscular Dystrophy: A Case Report.

Tracheo-innominate artery fistula (TIF) is a rare, life-threatening complication of tracheostomy that makes it difficult to secure the airway due to massive bleeding, constituting a medical emergency. Therefore, most successful surgical treatments include innominate artery debridement and tracheal fistula repair. Herein, we report a case of successful surgical treatment of a TIF while maintaining cerebral blood flow through an artificial vascular graft.

    Tracheo-innominate artery fistula (TIF)
    SYMPTOMS

 is a rare,

    life-threatening
    SYMPTOMS

 complication of

    tracheostomy
    MEDICATION

 that makes it

    difficult to secure the airway
    NEG_FINDINGS

 due to

    massive bleeding
    SYMPTOMS

, constituting a medical emergency. Therefore, most successful surgical treatments include

    innominate artery debridement
    MEDICATION

 and

    tracheal fistula repair
    MEDICATION

. Herein, we report a case of

    successful surgical treatment of a TIF
    MEDICATION

 while

    maintaining cerebral blood flow through an artificial vascular graft
    MEDICATION

.

Tracheo-innominate artery fistula (TIF)
life-threatening
massive bleeding


[Family genetic analysis of paternal Dystrophin gene mutations in a case of female Duchenne muscular dystrophy].

A pedigree genetic analysis of a female Duchenne muscular dystrophy (DMD) inherited from paternal chimerism was conducted to explore the genetic diagnosis strategy. No large deletions/duplications was found in the DMD gene of the proband. Next-generation sequencing (NGS) results showed that the proband had a heterozygous mutation in the DMD gene c.4707C>A (p.C1569X). This locus has not been reported in the literature and is considered as a pathogenic mutation. Sanger sequencing revealed that the father of the proband carried the same mutation, and the mosaic ratio was about 17.7%. The specific enzyme digestion test showed that the proband had maternal skewed X-inactivation. DMD a recessive inherited disease of the X chromosome, exists in female patients, and very few of them are inherited from paternal origin. Female patients need to pay close attention to skewed X-inactivation and suspected new mutations. Mosaic is not excluded, especially the inheritance of paternal mosaicism with normal phenotype. Prenatal gene screening is necessary for reproduction.

A

    pedigree genetic analysis
    PARACLINICAL

 of a

    female
    GENDER

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

    inherited from paternal chimerism
    FAMILY

 was conducted to explore the genetic diagnosis strategy.

    No large deletions/duplications was found in the DMD gene of the proband
    NEG_FINDINGS

.

    Next-generation sequencing (NGS) results
    PARACLINICAL

 showed that the

    proband
    GENDER

 had a

    heterozygous mutation in the DMD gene c.4707C>A (p.C1569X)
    GENETICS

. This locus has not been reported in the literature and is considered as a pathogenic mutation.

    Sanger sequencing
    PARACLINICAL

 revealed that

    the father of the proband carried the same mutation
    FAMILY

, and the

    mosaic ratio was about 17.7%
    GENETICS

. The

    specific enzyme digestion test
    PARACLINICAL

 showed that the

    proband
    GENDER

 had

    maternal skewed X-inactivation
    GENETICS

.

    DMD
    DIAGNOSIS

 a

    recessive inherited disease of the X chromosome
    GENETICS

, exists in

    female
    GENDER

 patients, and very few of them are

    inherited from paternal origin
    GENETICS

.

    Female
    GENDER

 patients need to pay close attention to

    skewed X-inactivation
    GENETICS

 and suspected new mutations.

    Mosaic
    DIAGNOSIS

 is not excluded, especially the

    inheritance of paternal mosaicism
    FAMILY

 with normal phenotype.

    Prenatal gene screening
    PARACLINICAL

 is necessary for

    reproduction
    MEDICATION

.

Duchenne muscular dystrophy (DMD)
DMD
Mosaic


Co-Occurrence of Fragile X Syndrome with a Second Genetic Condition: Three Independent Cases of Double Diagnosis.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism caused by the instability of a CGG trinucleotide repeat in exon 1 of the FMR1 gene. The co-occurrence of FXS with other genetic disorders has only been occasionally reported. Here, we describe three independent cases of FXS co-segregation with three different genetic conditions, consisting of Duchenne muscular dystrophy (DMD), PPP2R5D--related neurodevelopmental disorder, and 2p25.3 deletion. The co-occurrence of DMD and FXS has been reported only once in a young boy, while in an independent family two affected boys were described, the elder diagnosed with FXS and the younger with DMD. This represents the second case in which both conditions coexist in a 5-year-old boy, inherited from his heterozygous mother. The next double diagnosis had never been reported before: through exome sequencing, a girl with FXS who was of 7 years of age with macrocephaly and severe psychomotor delay was found to carry a de novo variant in the PPP2R5D gene. Finally, a maternally inherited 2p25.3 deletion associated with a decreased level of the MYT1L transcript, only in the patient, was observed in a 33-year-old FXS male with severe seizures compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by FXS and vice versa.

    Fragile X syndrome (FXS)
    DIAGNOSIS

 is the most common form of

    inherited intellectual disability
    GENETICS

 and

    autism
    DIAGNOSIS

 caused by the

    instability of a CGG trinucleotide repeat in exon 1 of the FMR1 gene
    GENETICS

. The

    co-occurrence of FXS with other genetic disorders
    DIAGNOSIS

 has only been occasionally reported. Here, we describe three independent cases of

    FXS
    DIAGNOSIS

    co-segregation with three different genetic conditions
    FAMILY

, consisting of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

,

    PPP2R5D--related neurodevelopmental disorder
    DIAGNOSIS

, and

    2p25.3 deletion
    GENETICS

. The

    co-occurrence of DMD and FXS
    FAMILY

 has been reported only once in a

    young
    AGE

    boy
    GENDER

, while in an

    independent family two affected boys
    FAMILY

    were described, the elder diagnosed with FXS and the younger with DMD
    FAMILY

. This represents the second case in which

    both conditions coexist in a 5-year-old
    FAMILY

    boy
    GENDER

,

    inherited from his heterozygous mother
    FAMILY

. The next double diagnosis had never been reported before: through

    exome sequencing
    PARACLINICAL

, a

    girl
    GENDER

 with

    FXS
    DIAGNOSIS

 who was

    of 7 years of age
    AGE

 with

    macrocephaly
    SYMPTOMS

 and

    severe psychomotor delay
    SYMPTOMS

 was found to carry a

    de novo variant in the PPP2R5D gene
    GENETICS

. Finally, a

    maternally inherited 2p25.3 deletion associated with a decreased level of the MYT1L transcript
    GENETICS

, only in the patient, was observed in a

    33-year-old
    AGE

    FXS
    DIAGNOSIS

    male
    GENDER

 with

    severe seizures
    SYMPTOMS

 compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by

    FXS
    DIAGNOSIS

 and vice versa.

macrocephaly
severe psychomotor delay
severe seizures


The identification of a novel splicing mutation in the DMD gene of a Chinese family.

The proband is a five-year-old boy diagnosed with Duchenne muscular dystrophy (DMD) by clinical manifestations and laboratory examination, but clinical phenotype of his parents is normal. In the study, his mother had a second pregnancy, and they went to obstetrics for genetic counseling to make informed reproductive choices.

The proband is a

    five-year-old
    AGE

    boy
    GENDER

 diagnosed with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 by clinical manifestations and

    laboratory examination
    PARACLINICAL

, but

    clinical phenotype of his parents is normal
    NEG_FINDINGS

. In the study,

    his
    GENDER

    mother had a second pregnancy
    FAMILY

, and they went to

    obstetrics
    MEDICATION

 for

    genetic counseling
    MEDICATION

 to make

    informed reproductive choices
    MEDICATION

.

obstetrics
genetic counseling
informed reproductive choices


To increase body height and muscle strength - one medicine for two diseases? Case report of a boy with Silver-Russell syndrome and Duchenne muscular dystrophy.

The coexistence of 2 genetic diseases can mutually modify their course. We describe the case of a 10-year-old boy with Sliver-Russell syndrome (SRS) and Duchenne muscular dystrophy (DMD). The patient's short stature, which is part of the clinical picture of both diseases, has been additionally aggravated by the steroid therapy, which is necessary to delay the progression of DMD. From the age of 9 years, the patient was treated with recombinant human growth hormone (rhGH) for 18 months. The following study discusses whether rhGH therapy in a child with SRS and DMD may alleviate or worsen the course of DMD, and how it affects carbohydrate metabolism disorders.

The

    coexistence of 2 genetic diseases
    DIAGNOSIS

 can mutually modify their course. We describe the case of a

    10-year-old
    AGE

    boy
    GENDER

 with

    Sliver-Russell syndrome (SRS)
    DIAGNOSIS

 and

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. The patient's

    short stature
    SYMPTOMS

, which is part of the clinical picture of both diseases, has been additionally aggravated by the

    steroid therapy
    MEDICATION

, which is necessary to delay the progression of

    DMD
    DIAGNOSIS

. From the

    age of 9 years
    AGE

, the patient was

    treated with recombinant human growth hormone (rhGH) for 18 months
    MEDICATION

. The following study discusses whether

    rhGH therapy
    MEDICATION

 in a

    child
    AGE

 with

    SRS
    DIAGNOSIS

 and

    DMD
    DIAGNOSIS

 may alleviate or worsen the course of

    DMD
    DIAGNOSIS

, and how it affects

    carbohydrate metabolism disorders
    DIAGNOSIS

.

coexistence of 2 genetic diseases
Sliver-Russell syndrome (SRS)
Duchenne muscular dystrophy (DMD)
DMD
SRS
DMD
DMD
carbohydrate metabolism disorders


Anesthetic management with remimazolam for a pediatric patient with Duchenne muscular dystrophy.

With Duchenne muscular dystrophy (DMD) being the most common and most severe type of muscular dystrophy, DMD patients are at risk for complications from general anesthesia due to impaired cardiac and respiratory functions as the pathological condition progresses. In recent years, advances in multidisciplinary treatment have improved the prognosis of DMD patients, and the number of patients requiring surgery has increased. Remimazolam is a benzodiazepine derivative similar to midazolam. Its circulatory stability and the fact that it has an antagonist make it superior to propofol.There are no reports of pediatric patients with DMD undergoing total intravenous anesthesia with remimazolam.

A 4-year boy was scheduled for single-incision laparoscopic percutaneous extraperitoneal closure for inguinal hernia under general anesthesia, but the surgery was postponed because his serum creatine phosphokinase level was extremely high.

He was diagnosed with DMD. According to the results of the genetic test, exon deletion of the DMD gene was detected using multiplex ligation-dependent probe amplification, although he had no symptoms of DMD except for elevated serum levels of creatine phosphokinase, etc.

He was admitted for the same surgical purpose. Anesthesia was induced with 3 mg of intravenously administered remimazolam. He lost the ability to respond to verbal commands. After the intravenous administration of 100 μg of fentanyl, a continuous infusion of remifentanil (1.0 μg/kg/min) and remimazolam (15 mg/h) was started, and the endotracheal tube was inserted smoothly after the administration of 10 mg of rocuronium with which the muscle twitches disappeared in train-of-four monitoring. At the end of the surgery, 15 mg of flurbiprofen was administered intravenously. After surgery, we injected 40 mg of sugammadex to confirm a train-of-four count of 100%.

Although the dose of remimazolam was reduced to 5 mg/h 30 minutes before the end of the surgery, it took 20 minutes after the discontinuation of remimazolam for the patient to open his eyes upon verbal command. On postoperative Day 2, he was discharged from the hospital without any complications.

Remimazolam was shown to be safe to use for general anesthesia in a pediatric patient with DMD.

With

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 being the most common and most severe type of

    muscular dystrophy
    DIAGNOSIS

,

    DMD
    DIAGNOSIS

 patients are at risk for complications from

    general anesthesia
    MEDICATION

 due to

    impaired cardiac and respiratory functions
    SYMPTOMS

 as the pathological condition progresses. In recent years, advances in

    multidisciplinary treatment
    MEDICATION

 have improved the prognosis of

    DMD
    DIAGNOSIS

 patients, and the number of patients requiring

    surgery
    MEDICATION

 has increased.

    Remimazolam is a benzodiazepine derivative similar to midazolam
    MEDICATION

. Its

    circulatory stability
    SYMPTOMS

 and the fact that it has an

    antagonist
    MEDICATION

 make it superior to

    propofol
    MEDICATION

.There are no reports of

    pediatric
    AGE

 patients with

    DMD
    DIAGNOSIS

 undergoing

    total intravenous anesthesia with remimazolam
    MEDICATION

.

A

    4-year boy
    AGE

 was scheduled for

    single-incision laparoscopic percutaneous extraperitoneal closure for inguinal hernia
    MEDICATION

 under

    general anesthesia
    MEDICATION

, but the

    surgery
    MEDICATION

 was postponed because

    his
    GENDER

    serum creatine phosphokinase level was extremely high
    BIOCHEMICAL

.

    He
    GENDER

 was diagnosed with

    DMD
    DIAGNOSIS

. According to the results of the

    genetic test
    PARACLINICAL

,

    exon deletion of the DMD gene
    GENETICS

 was detected using

    multiplex ligation-dependent probe amplification
    PARACLINICAL

,

    although he had no symptoms of DMD
    NEG_FINDINGS

 except for

    elevated serum levels of creatine phosphokinase, etc.
    BIOCHEMICAL

    He
    GENDER

 was admitted for the same

    surgical purpose
    MEDICATION

.

    Anesthesia
    MEDICATION

 was induced with

    3 mg of intravenously administered remimazolam
    MEDICATION

.

    He
    GENDER

    lost the ability to respond to verbal commands
    NEG_FINDINGS

. After the

    intravenous administration of 100 μg of fentanyl
    MEDICATION

, a

    continuous infusion of remifentanil (1.0 μg/kg/min) and remimazolam (15 mg/h)
    MEDICATION

 was started, and the

    endotracheal tube was inserted
    MEDICATION

 smoothly after the

    administration of 10 mg of rocuronium
    MEDICATION

 with which the

    muscle twitches disappeared in train-of-four monitoring
    SYMPTOMS

. At the end of the

    surgery
    MEDICATION

,

    15 mg of flurbiprofen was administered intravenously
    MEDICATION

. After

    surgery
    MEDICATION

, we

    injected 40 mg of sugammadex
    MEDICATION

 to confirm a

    train-of-four count of 100%
    PARACLINICAL

.

    Although the dose of remimazolam was reduced to 5 mg/h 30 minutes before the end of the surgery
    MEDICATION

, it took 20 minutes after the

    discontinuation of remimazolam
    MEDICATION

 for the patient to

    open his eyes upon verbal command
    NEG_FINDINGS

. On postoperative Day 2,

    he
    GENDER

 was

    discharged from the hospital without any complications
    MEDICATION

.

    Remimazolam
    MEDICATION

 was shown to be safe to use for

    general anesthesia
    MEDICATION

 in a

    pediatric
    AGE

 patient with

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
muscular dystrophy
DMD
DMD
DMD
DMD
DMD


Early Identification of DMD in the Setting of West Syndrome.

Duchene muscular dystrophy (DMD) is the most common muscular dystrophy in childhood, affecting ∼1:5000 male live births worldwide. DMD is a genetic disorder with X-linked recessive inheritance pattern characterized by a severe muscular phenotype with progressive muscle weakness and atrophy due to pathogenic variations within the DMD gene. Two cases are reported to date in the literature of individuals with a diagnosis of both DMD and West syndrome; neither of which had the degree of additional genetic abnormalities that our patient demonstrates. We present a male infant with West syndrome, and multiple pathogenic variants, the ominous one being in the DMD gene. This case adds to confirming that West syndrome expands the spectrum of epilepsy that may be present in DMD patients. Additionally, this case can identify how the early use of steroids may shed light on effects of early symptomatic treatment of DMD.

    Duchene muscular dystrophy (DMD)
    DIAGNOSIS

 is the most common

    muscular dystrophy
    DIAGNOSIS

 in

    childhood
    AGE

, affecting ∼1:5000

    male
    GENDER

 live births worldwide.

    DMD
    DIAGNOSIS

 is a

    genetic disorder
    GENETICS

 with

    X-linked recessive inheritance pattern
    GENETICS

 characterized by a

    severe muscular phenotype
    SYMPTOMS

 with

    progressive muscle weakness
    SYMPTOMS

 and

    atrophy
    SYMPTOMS

 due to

    pathogenic variations within the DMD gene
    GENETICS

. Two cases are reported to date in the literature of individuals with a diagnosis of both

    DMD
    DIAGNOSIS

 and

    West syndrome
    DIAGNOSIS

; neither of which had the degree of additional genetic abnormalities that our patient demonstrates. We present a

    male
    GENDER

    infant
    AGE

 with

    West syndrome
    DIAGNOSIS

, and

    multiple pathogenic variants, the ominous one being in the DMD gene
    GENETICS

. This case adds to confirming that

    West syndrome
    DIAGNOSIS

 expands the spectrum of

    epilepsy
    DIAGNOSIS

 that may be present in

    DMD
    DIAGNOSIS

 patients. Additionally, this case can identify how the

    early use of steroids
    MEDICATION

 may shed light on effects of

    early symptomatic treatment
    MEDICATION

 of

    DMD
    DIAGNOSIS

.

Duchene muscular dystrophy (DMD)
muscular dystrophy
DMD
DMD
West syndrome
West syndrome
West syndrome
epilepsy
DMD
DMD

severe muscular phenotype
progressive muscle weakness
atrophy

early use of steroids
early symptomatic treatment


Rhabdomyosarcoma in a Patient With Duchenne Muscular Dystrophy: A Possible Association.

Duchenne muscular dystrophy (DMD), caused by a mutation in the DMD gene, is known to be associated with co-morbidities including cardiomyopathy, respiratory failure, neuromuscular scoliosis and intellectual disability. Animal studies have explored the susceptibility of dystrophin-deficient mice with the development of myogenic tumors. While there is adequate literature describing both DMD and rhabdomyosarcoma (RMS) separately, there has yet to be a comprehensive literature review investigating the possibility that patients with DMD may be at a higher risk of developing RMS and other myogenic tumors. We present the case of a pediatric patient with DMD who developed alveolar RMS and review the literature for susceptibility to development of myogenic tumors in cases of DMD gene mutation.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, caused by a

    mutation in the DMD gene
    GENETICS

, is known to be associated with co-morbidities including

    cardiomyopathy
    SYMPTOMS

,

    respiratory failure
    SYMPTOMS

,

    neuromuscular scoliosis
    SYMPTOMS

 and

    intellectual disability
    SYMPTOMS

. Animal studies have explored the susceptibility of

    dystrophin-deficient
    GENETICS

 mice with the development of

    myogenic tumors
    DIAGNOSIS

. While there is adequate literature describing both

    DMD
    DIAGNOSIS

 and

    rhabdomyosarcoma (RMS)
    DIAGNOSIS

 separately, there has yet to be a comprehensive literature review investigating the possibility that patients with

    DMD
    DIAGNOSIS

 may be at a higher risk of developing

    RMS
    DIAGNOSIS

 and other

    myogenic tumors
    DIAGNOSIS

. We present the case of a

    pediatric
    AGE

 patient with

    DMD
    DIAGNOSIS

 who developed

    alveolar RMS
    DIAGNOSIS

 and review the literature for susceptibility to development of

    myogenic tumors
    DIAGNOSIS

 in cases of

    DMD gene mutation
    GENETICS

.

Duchenne muscular dystrophy (DMD)
myogenic tumors
DMD
rhabdomyosarcoma (RMS)
DMD
RMS
myogenic tumors
DMD
alveolar RMS
myogenic tumors

mutation in the DMD gene
dystrophin-deficient
DMD gene mutation

cardiomyopathy
respiratory failure
neuromuscular scoliosis
intellectual disability


Non-compaction cardiomyopathy, Becker muscular dystrophy, neuropathy and recurrent syncope.

We present the case of a 50-year-old man presenting with new heart failure symptoms. He had no evidence of any ischaemic cardiomyopathy, however, further cardiac imaging showed a left ventricular non-compaction cardiomyopathy. He was noted to have muscular weakness and an exhaustive search for associated comorbidities yielded a diagnosis of Becker muscular dystrophy. In this report, we review the pathophysiology, comorbidities and diagnostic workup in patients presenting with left ventricular non-compaction in the context of dystrophinopathy. Ultimately, we suggest the consideration of rare cardiomyopathies in all patients presenting with neuromuscular syndromes and vice versa.

We present the case of a

    50-year-old
    AGE

    man
    GENDER

 presenting with

    new heart failure symptoms
    SYMPTOMS

.

    He
    GENDER

 had

    no evidence of any ischaemic cardiomyopathy
    NEG_FINDINGS

, however, further

    cardiac imaging
    PARACLINICAL

 showed a

    left ventricular non-compaction cardiomyopathy
    SYMPTOMS

.

    He
    GENDER

 was noted to have

    muscular weakness
    SYMPTOMS

 and an exhaustive search for associated comorbidities yielded a diagnosis of

    Becker muscular dystrophy
    DIAGNOSIS

. In this report, we review the pathophysiology, comorbidities and diagnostic workup in patients presenting with

    left ventricular non-compaction
    SYMPTOMS

 in the context of

    dystrophinopathy
    DIAGNOSIS

. Ultimately, we suggest the consideration of

    rare cardiomyopathies
    DIAGNOSIS

 in all patients presenting with

    neuromuscular syndromes
    DIAGNOSIS

 and vice versa.

Becker muscular dystrophy
dystrophinopathy
rare cardiomyopathies
neuromuscular syndromes


Complex glycerol kinase deficiency - long-term follow-up of two patients.

Complex glycerol kinase deficiency (CGKD) is a rare genetic syndrome which belongs to the group of contiguous gene syndromes and is caused by microdeletion of genes located in Xp21. Patients with CGKD present with features characteristic for adrenal hypoplasia, glycerol kinase deficiency, Duchenne muscular dystrophy and sometimes intellectual disability. We present a long-term follow-up of two unrelated boys with molecular diagnosis of complex glycerol kinase deficiency. Genetic examinations in both patients revealed a deletion on Xp21 chromosome including complete deletion of NR0B1 and GK genes. Additionally in patient 2 IL1RAPL1 genes were deleted. In separate MLPA test DMD gene deletion was diagnosed in both patients as follow: in patient 1 whole gene while in patient 2 the C-terminal region of DMD was deleted. Although the first symptom in both was salt loss syndrome, the course of the disease was different for them. We share our experience resulting from the opportunity of caring for patients with this rare disease from the beginning of their life to the end of pediatric care.

    Complex glycerol kinase deficiency (CGKD)
    DIAGNOSIS

 is a

    rare genetic syndrome
    DIAGNOSIS

 which belongs to the group of

    contiguous gene syndromes
    DIAGNOSIS

 and is caused by

    microdeletion of genes located in Xp21
    GENETICS

. Patients with

    CGKD
    DIAGNOSIS

 present with features characteristic for

    adrenal hypoplasia
    SYMPTOMS

,

    glycerol kinase deficiency
    BIOCHEMICAL

,

    Duchenne muscular dystrophy
    DIAGNOSIS

 and sometimes

    intellectual disability
    SYMPTOMS

. We present a long-term follow-up of two unrelated

    boys
    GENDER

 with

    molecular diagnosis
    PARACLINICAL

 of

    complex glycerol kinase deficiency
    DIAGNOSIS

.

    Genetic examinations
    PARACLINICAL

 in both patients revealed a

    deletion on Xp21 chromosome
    GENETICS

 including

    complete deletion of NR0B1 and GK genes
    GENETICS

. Additionally in patient 2

    IL1RAPL1 genes were deleted
    GENETICS

. In separate

    MLPA test
    PARACLINICAL

    DMD gene deletion
    GENETICS

 was diagnosed in both patients as follow: in patient 1

    whole gene
    GENETICS

 while in patient 2

    the C-terminal region of DMD was deleted
    GENETICS

. Although the first symptom in both was

    salt loss syndrome
    SYMPTOMS

, the course of the disease was different for them. We share our experience resulting from the opportunity of caring for patients with this

    rare disease
    DIAGNOSIS

 from the beginning of their life to the end of pediatric care.

adrenal hypoplasia
intellectual disability
salt loss syndrome


Becker muscular dystrophy: case report, review of the literature, and analysis of differentially expressed hub genes.

Becker muscular dystrophy (BMD) is a genetic and progressive neuromuscular disease caused by mutations in the dystrophin gene with no available cure. A case report and comprehensive review of BMD cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from microarray data of muscle samples from patients with BMD help uncover the potential mechanism and provide novel therapeutic targets for dystrophin-deficient muscular dystrophies.

We describe a BMD family with a 10-year-old boy as the proband and reviewed BMD cases from PubMed. Datasets from the Gene Expression Omnibus database were downloaded and integrated with the online software.

The systematic review revealed the clinical manifestations and mutation points of the dystrophin gene. Gene ontology analysis showed that extracellular matrix organization and extracellular structure organization with enrichment of upregulated genes coexist in three datasets. We present the first report of TUBA1A involvement in the development of BMD/Duchenne muscular dystrophy (DMD).

This study provides important implications for clinical practice, uncovering the potential mechanism of the progress of BMD/DMD, and provided new therapeutic targets.

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 is a

    genetic and progressive neuromuscular disease
    DIAGNOSIS

 caused by

    mutations in the dystrophin gene
    GENETICS

 with

    no available cure
    NEG_FINDINGS

. A case report and comprehensive review of

    BMD
    DIAGNOSIS

 cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from

    microarray data of muscle samples
    PARACLINICAL

 from patients with

    BMD
    DIAGNOSIS

 help uncover the potential mechanism and provide novel therapeutic targets for

    dystrophin-deficient muscular dystrophies
    DIAGNOSIS

.

We describe a

    BMD
    DIAGNOSIS

    family with a 10-year-old
    FAMILY

    boy
    GENDER

 as the proband and reviewed

    BMD
    DIAGNOSIS

 cases from PubMed. Datasets from the Gene Expression Omnibus database were downloaded and integrated with the online software.

The systematic review revealed the clinical manifestations and

    mutation points of the dystrophin gene
    GENETICS

.

    Gene ontology analysis
    PARACLINICAL

 showed that

    extracellular matrix organization and extracellular structure organization
    MICROSCOPIC

 with

    enrichment of upregulated genes
    MICROSCOPIC

 coexist in three datasets. We present the first report of

    TUBA1A
    GENETICS

 involvement in the development of

    BMD/Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

.

This study provides important implications for clinical practice, uncovering the potential mechanism of the progress of

    BMD/DMD
    DIAGNOSIS

, and provided new therapeutic targets.

mutations in the dystrophin gene
mutation points of the dystrophin gene
TUBA1A


A rare co-occurrence of duchenne muscular dystrophy, congenital adrenal hypoplasia and glycerol kinase deficiency due to Xp21 contiguous gene deletion syndrome: case report.

Contiguous gene deletion syndromes are rare genomic disorders caused by deletion of large segments of DNA resulting in co-occurrence of apparently unrelated multiple clinical phenotypes. We report a boy with contiguous gene deletion involving Xp21 genomic location.

A Sri Lankan boy with developmental delay and failure to thrive first presented at three years of age with hypovolaemia, hyperpigmentation and drowsiness. Investigations done at that time revealed hypoglycaemia, hyponatraemia, hyperkalaemia, low cortisol, low aldosterone, high ACTH and low 17-hydroxyprogesterone. He was diagnosed to have primary adrenal insufficiency. During follow-up at five years, he was noted to have progressive difficulty in walking, waddling gait, hypotonia, calf hypertrophy and positive Gower's sign. His creatine kinase was very high, and the electromyogram showed myopathy. Genetic analysis revealed hemizygous deletion involving the final 35 exons of the dystrophin gene confirming the diagnosis of Duchenne muscular dystrophy. Further investigations revealed pseudohypertriglyceridemia, large glycerol peak on urine organic acid analysis and hemizygous deletion of the glycerol kinase gene confirming glycerol kinase deficiency. Based on the presence of Duchenne muscular dystrophy, glycerol kinase deficiency and probable congenital adrenal hypoplasia along with genetic confirmation of deletions involving dystrophin and glycerol kinase genes, the diagnosis of Xp21 contiguous gene deletion syndrome was made.

We report a child with contiguous gene deletion syndrome who was initially diagnosed as having isolated primary adrenal insufficiency probably due to congenital adrenal hypoplasia. Later he was confirmed to have Duchenne muscular dystrophy and glycerol kinase deficiency, as well. This case report highlights the importance of pre-emptive evaluation and identification of genetic defects when patients present with seemingly unrelated diseases that could aid in accurate diagnoses of contiguous gene deletion syndromes.

    Contiguous gene deletion syndromes
    DIAGNOSIS

 are

    rare genomic disorders
    GENETICS

 caused by

    deletion of large segments of DNA
    GENETICS

 resulting in

    co-occurrence of apparently unrelated multiple clinical phenotypes
    FAMILY

. We report a

    boy
    GENDER

 with

    contiguous gene deletion involving Xp21 genomic location
    GENETICS

.

A

    Sri Lankan
    ETHNICITY

    boy
    GENDER

 with

    developmental delay
    SYMPTOMS

 and

    failure to thrive
    SYMPTOMS

 first presented at

    three years of age
    AGE

 with

    hypovolaemia
    BIOCHEMICAL

,

    hyperpigmentation
    SYMPTOMS

 and

    drowsiness
    SYMPTOMS

. Investigations done at that time revealed

    hypoglycaemia
    BIOCHEMICAL

,

    hyponatraemia
    BIOCHEMICAL

,

    hyperkalaemia
    BIOCHEMICAL

,

    low cortisol, low aldosterone
    BIOCHEMICAL

,

    high ACTH
    BIOCHEMICAL

 and

    low 17-hydroxyprogesterone
    BIOCHEMICAL

.

    He
    GENDER

 was diagnosed to have

    primary adrenal insufficiency
    DIAGNOSIS

. During

    follow-up
    PARACLINICAL

 at

    five years
    AGE

,

    he
    GENDER

 was noted to have

    progressive difficulty in walking
    SYMPTOMS

,

    waddling gait
    SYMPTOMS

,

    hypotonia
    SYMPTOMS

,

    calf hypertrophy
    SYMPTOMS

 and

    positive Gower's sign
    SYMPTOMS

. His

    creatine kinase was very high
    BIOCHEMICAL

, and the

    electromyogram
    PARACLINICAL

 showed

    myopathy
    SYMPTOMS

.

    Genetic analysis
    PARACLINICAL

 revealed

    hemizygous deletion involving the final 35 exons of the dystrophin gene
    GENETICS

 confirming the diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

. Further investigations revealed

    pseudohypertriglyceridemia
    BIOCHEMICAL

,

    large glycerol peak on urine organic acid analysis
    BIOCHEMICAL

 and

    hemizygous deletion of the glycerol kinase gene
    GENETICS

 confirming

    glycerol kinase deficiency
    BIOCHEMICAL

. Based on the presence of

    Duchenne muscular dystrophy
    DIAGNOSIS

,

    glycerol kinase deficiency
    BIOCHEMICAL

 and

    probable congenital adrenal hypoplasia
    SYMPTOMS

 along with genetic confirmation of

    deletions involving dystrophin and glycerol kinase genes
    GENETICS

, the diagnosis of

    Xp21 contiguous gene deletion syndrome
    DIAGNOSIS

 was made.

We report a

    child
    AGE

 with

    contiguous gene deletion syndrome
    DIAGNOSIS

 who was initially diagnosed as having

    isolated primary adrenal insufficiency
    SYMPTOMS

 probably due to

    congenital adrenal hypoplasia
    NEG_FINDINGS

. Later

    he
    GENDER

 was confirmed to have

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    glycerol kinase deficiency
    BIOCHEMICAL

, as well. This case report highlights the importance of pre-emptive evaluation and identification of

    genetic defects
    GENETICS

 when patients present with seemingly unrelated diseases that could aid in accurate diagnoses of

    contiguous gene deletion syndromes
    DIAGNOSIS

.

Contiguous gene deletion syndromes
primary adrenal insufficiency
Duchenne muscular dystrophy
Duchenne muscular dystrophy
Xp21 contiguous gene deletion syndrome
contiguous gene deletion syndrome
Duchenne muscular dystrophy
contiguous gene deletion syndromes

developmental delay
failure to thrive
hyperpigmentation
drowsiness
progressive difficulty in walking
waddling gait
hypotonia
calf hypertrophy
positive Gower's sign
myopathy
probable congenital adrenal hypoplasia
isolated primary adrenal insufficiency


Autism Spectrum Disorder and Duchenne Muscular Dystrophy: A Clinical Case on the Potential Role of the Dystrophin in Autism Neurobiology.

A diagnosis of autism spectrum disorder is reported in up to 19% of dystrophinopathies. However, over the last ten years, only a few papers have been published on this topic. Therefore, further studies are required to analyze this association in depth and ultimately to understand the role of the brain dystrophin isoform in the pathogenesis of ASD and other neurodevelopmental disorders. In this paper, we report a clinical case of a patient affected by ASD and Duchenne muscular dystrophy, who carries a large deletion of the dystrophin gene. Then we present a brief overview of the literature about similar cases and about the potential role of the dystrophin protein in the neurobiology of autism spectrum disorder.

A diagnosis of

    autism spectrum disorder
    DIAGNOSIS

 is reported in up to 19% of

    dystrophinopathies
    DIAGNOSIS

. However, over the last ten years, only a few papers have been published on this topic. Therefore, further studies are required to analyze this association in depth and ultimately to understand the role of the brain dystrophin isoform in the pathogenesis of

    ASD
    DIAGNOSIS

 and other

    neurodevelopmental disorders
    DIAGNOSIS

. In this paper, we report a clinical case of a patient affected by

    ASD
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

, who carries a

    large deletion of the dystrophin gene
    GENETICS

. Then we present a brief overview of the literature about similar cases and about the potential role of the dystrophin protein in the neurobiology of

    autism spectrum disorder
    DIAGNOSIS

.

autism spectrum disorder
dystrophinopathies
ASD
neurodevelopmental disorders
ASD
Duchenne muscular dystrophy
autism spectrum disorder


Acute perimyocarditis mimicking acute myocardial infarction in a 12-year-old boy with duchenne muscular dystrophy: a case report.

Differential diagnosis of chest pain in the pediatric population is important but can be challenging. A 12-year-old boy with Duchenne muscular dystrophy presented with chest pain, cardiac enzyme elevation, and convex ST elevations in the inferior leads with reciprocal ST depression in the anterior leads on electrocardiogram. Echocardiography on admission revealed normal left ventricular function. Suspecting acute myocardial infarction, we performed invasive coronary angiography, which revealed normal coronary arteries. A follow-up electrocardiogram showed an acute pericarditis pattern with concave ST elevations in most leads and PR depression, and follow-up echocardiography revealed global left ventricular dysfunction, suggestive of acute perimyocarditis. Ibuprofen was administered for acute pericarditis, and a continuous milrinone infusion was commenced for myocardial dysfunction. The chest pain improved by the next day, and the ST segment elevations normalized on day 4. Echocardiography on day 9 revealed improved left ventricular function. The patient was discharged on day 11, and he is doing well without chest pain through 12 months of follow-up. The last electrocardiogram showed normal sinus rhythm without ST change. Differential diagnosis of acute myocardial infarction and acute perimyocarditis is important for proper treatment strategies and the different prognoses of these two conditions.

    Differential diagnosis
    PARACLINICAL

 of

    chest pain
    SYMPTOMS

 in the

    pediatric
    AGE

 population is important but can be challenging. A

    12-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 presented with

    chest pain
    SYMPTOMS

,

    cardiac enzyme elevation
    BIOCHEMICAL

, and

    convex ST elevations in the inferior leads with reciprocal ST depression in the anterior leads
    SYMPTOMS

 on

    electrocardiogram
    PARACLINICAL

.

    Echocardiography
    PARACLINICAL

 on admission revealed

    normal left ventricular function
    NEG_FINDINGS

. Suspecting

    acute myocardial infarction
    SYMPTOMS

, we performed

    invasive coronary angiography
    PARACLINICAL

, which revealed

    normal coronary arteries
    NEG_FINDINGS

. A

    follow-up electrocardiogram
    PARACLINICAL

 showed an

    acute pericarditis pattern
    SYMPTOMS

 with

    concave ST elevations in most leads and PR depression
    SYMPTOMS

, and

    follow-up echocardiography
    PARACLINICAL

 revealed

    global left ventricular dysfunction
    SYMPTOMS

, suggestive of

    acute perimyocarditis
    DIAGNOSIS

.

    Ibuprofen
    MEDICATION

 was administered for

    acute pericarditis
    DIAGNOSIS

, and a

    continuous milrinone infusion
    MEDICATION

 was commenced for

    myocardial dysfunction
    SYMPTOMS

. The

    chest pain improved
    SYMPTOMS

 by the next day, and the

    ST segment elevations normalized
    SYMPTOMS

 on day 4.

    Echocardiography
    PARACLINICAL

 on day 9 revealed

    improved left ventricular function
    SYMPTOMS

. The patient was discharged on day 11, and

    he
    GENDER

 is doing well

    without chest pain
    NEG_FINDINGS

 through 12 months of follow-up. The last electrocardiogram showed

    normal sinus rhythm without ST change
    NEG_FINDINGS

.

    Differential diagnosis
    PARACLINICAL

 of

    acute myocardial infarction
    DIAGNOSIS

 and

    acute perimyocarditis
    DIAGNOSIS

 is important for proper treatment strategies and the different prognoses of these two conditions.

Duchenne muscular dystrophy
acute perimyocarditis
acute pericarditis
acute myocardial infarction
acute perimyocarditis

normal left ventricular function
normal coronary arteries
without chest pain
normal sinus rhythm without ST change


Non-invasive mechanical ventilation as an alternative respiratory support during gastrostomy tube placement, in a patient with Duchenne muscular dystrophy, 24/24 hours ventilation dependent.

Patients with Duchenne muscular dystrophy may benefit from gastrostomy tube feeding due to progressive dysphagia and malnutrition. However, due to concomitant pathologies, they are often at high risk for anesthesiologic complications. We describe how the non-invasive mechanical ventilation has been an alternative successful respiratory support option during the gastrostomy tube placement in a patient with Duchenne muscular dystrophy, on continuous NIV treatment. This report confirms how the use of NIV can support alveolar ventilation, before, during and after mini-invasive procedures, and prevent respiratory complications.

Patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 may benefit from

    gastrostomy tube feeding
    MEDICATION

 due to

    progressive dysphagia
    SYMPTOMS

 and

    malnutrition
    SYMPTOMS

. However, due to concomitant pathologies, they are often at high risk for

    anesthesiologic complications
    SYMPTOMS

. We describe how the

    non-invasive mechanical ventilation
    MEDICATION

 has been an alternative

    successful respiratory support option during the gastrostomy tube placement
    MEDICATION

 in a patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

, on

    continuous NIV treatment
    MEDICATION

. This report confirms how the

    use of NIV can support alveolar ventilation, before, during and after mini-invasive procedures
    MEDICATION

, and

    prevent respiratory complications
    SYMPTOMS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy

progressive dysphagia
malnutrition
anesthesiologic complications
prevent respiratory complications


Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East.

The timely and accurate genetic diagnosis of Duchenne muscular dystrophy (DMD) enables prompt initiation of disease management and genetic counseling and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of DMD, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with DMD in Middle Eastern countries and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of DMD. A lack of disease awareness and consequential failure to recognize the signs and symptoms of DMD significantly contributed to the delayed diagnoses of these patients. Additional challenges included limited available funding for genetic testing and a lack of local specialist and genetic testing centers, causing patients and their families to travel vast distances for appointments in some countries. Earlier and more accurate genetic diagnosis of DMD in this region would allow patients to benefit from effective disease management, leading to improvements in health-related quality of life.

The timely and accurate genetic diagnosis of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 enables

    prompt initiation of disease management and genetic counseling
    MEDICATION

 and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of

    DMD
    DIAGNOSIS

, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with

    DMD
    DIAGNOSIS

 in

    Middle Eastern countries
    ETHNICITY

 and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of

    DMD
    DIAGNOSIS

. A

    lack of disease awareness
    NEG_FINDINGS

 and consequential

    failure to recognize the signs and symptoms of DMD
    NEG_FINDINGS

 significantly contributed to the delayed diagnoses of these patients. Additional challenges included limited available funding for genetic testing and a lack of local specialist and genetic testing centers, causing patients and their families to travel vast distances for appointments in some countries. Earlier and more accurate genetic diagnosis of

    DMD
    DIAGNOSIS

 in this region would allow patients to benefit from effective disease management, leading to improvements in health-related quality of life.

Duchenne muscular dystrophy (DMD)
DMD
DMD
DMD
DMD


[Diagnosis of a patient with adjacent gene deletion syndrome with DMD complete deletion type of Duchenne muscular dystrophy].

To identify the etiology of a patient with severe symptoms of DMD and to trace its pathogenic gene, so as to provide a basis for genetic counseling and clinical intervention.

Multiple ligation-dependent probe amplification (MLPA) technique was used to analyze exon deletion/repetitive variant of DMD gene, and further analysis was performed by chromosome G-banding, fluorescence in situ hybridization (FISH) and SNP array analysis.

The MLPA results of the proband showed that the exon 1-79 of DMD gene were deleted, the G-banding karyotype of blood sample was 46, XY, and the deletion of the short arm of X chromosome was found by FISH. SNP array results showed that 5.8Mb (29 628 158-35 434 714) deletion occurred in the Xp21.2p21.1 region of X chromosome, and the patient was diagnosed as the contiguous deletion syndrome involving the genes of IL1RAPL, MAGEB1-4, ROB, CXorf2, GM, AP3K7IP, FTHL1, DMD, FAM47A, TMEM47, and FAM47B.

The exact pathogenic site of this family is the deletion of 5.8 Mb (29 628 158-35 434 714) in the Xp21.2p21.1 region of X chromosome, which can be used for prenatal diagnosis. High resolution SNP array technique plays an important role in detecting potential chromosome abnormalities in patients.

To identify the etiology of a patient with

    severe symptoms
    SYMPTOMS

 of

    DMD
    DIAGNOSIS

 and to trace its pathogenic gene, so as to provide a basis for

    genetic counseling
    MEDICATION

 and

    clinical intervention
    MEDICATION

.

    Multiple ligation-dependent probe amplification (MLPA) technique
    PARACLINICAL

 was used to

    analyze exon deletion/repetitive variant of DMD gene
    PARACLINICAL

, and further analysis was performed by

    chromosome G-banding
    PARACLINICAL

,

    fluorescence in situ hybridization (FISH)
    PARACLINICAL

 and

    SNP array analysis
    PARACLINICAL

.

The

    MLPA results
    PARACLINICAL

 of the proband showed that

    the exon 1-79 of DMD gene were deleted
    GENETICS

, the

    G-banding karyotype of blood sample
    PARACLINICAL

 was

    46, XY
    GENETICS

, and the

    deletion of the short arm of X chromosome
    GENETICS

 was found by

    FISH
    PARACLINICAL

.

    SNP array results
    PARACLINICAL

 showed that

    5.8Mb (29 628 158-35 434 714) deletion occurred in the Xp21.2p21.1 region of X chromosome
    GENETICS

, and the patient was diagnosed as the

    contiguous deletion syndrome
    DIAGNOSIS

    involving the genes of IL1RAPL, MAGEB1-4, ROB, CXorf2, GM, AP3K7IP, FTHL1, DMD, FAM47A, TMEM47, and FAM47B.
    GENETICS

The exact pathogenic site of this family is the

    deletion of 5.8 Mb (29 628 158-35 434 714) in the Xp21.2p21.1 region of X chromosome
    GENETICS

, which can be used for

    prenatal diagnosis
    PARACLINICAL

.

    High resolution SNP array technique
    PARACLINICAL

 plays an important role in detecting potential

    chromosome abnormalities
    GENETICS

 in patients.

genetic counseling
clinical intervention


Case Report: ISPD Gene Mutation Leads to Dystroglycanopathies: Genotypic Phenotype Analysis and Treatment Exploration.

ISPD gene mutation-related diseases have high clinical and genetic heterogeneity, and no studies have yet reported any effective treatments. We describe six patients with dystroglycanopathies caused by ISPD gene mutations and analyze their genotypes and phenotypes to explore possible effective treatments. Our results confirm that the phenotype of limb-girdle muscular dystrophies can be easily misdiagnosed as Duchenne muscular dystrophy and that exon deletions of ISPD gene are relatively common. Moreover, low-dose prednisone therapy can improve patients' exercise ability and prolong survival and may be a promising new avenue for ISPD therapy.

    ISPD gene mutation-related diseases
    GENETICS

 have high clinical and genetic heterogeneity, and no studies have yet reported any effective treatments. We describe six patients with

    dystroglycanopathies
    DIAGNOSIS

 caused by

    ISPD gene mutations
    GENETICS

 and analyze their genotypes and phenotypes to explore possible effective treatments. Our results confirm that the phenotype of

    limb-girdle muscular dystrophies
    DIAGNOSIS

 can be easily misdiagnosed as

    Duchenne muscular dystrophy
    DIAGNOSIS

 and that

    exon deletions of ISPD gene
    GENETICS

 are relatively common. Moreover,

    low-dose prednisone therapy
    MEDICATION

 can improve patients'

    exercise ability
    SYMPTOMS

 and

    prolong survival
    SYMPTOMS

 and may be a promising new avenue for

    ISPD therapy
    MEDICATION

.

ISPD gene mutation-related diseases
ISPD gene mutations
exon deletions of ISPD gene

dystroglycanopathies
limb-girdle muscular dystrophies
Duchenne muscular dystrophy

low-dose prednisone therapy
ISPD therapy


A novel DMD intronic alteration: a potentially disease-causing variant of an intermediate muscular dystrophy phenotype.

Pathogenic germline variants in DMD gene, which encodes the well-known cytoskeletal protein named dystrophin, are associated with a wide range of dystrophinopathies disorders, such as Duchenne muscular dystrophy (DMD, severe form), Becker muscular dystrophy (BMD, mild form) and intermediate muscular dystrophy (IMD). Muscle biopsy, immunohistochemistry, molecular (multiplex ligation-dependent probe amplification (MLPA)/next-generation sequencing (NGS) and Sanger methods) and in silico analyses were performed in order to identify alterations in DMD gene and protein in a patient with a clinical manifestation and with high creatine kinase levels. Herein, we described a previously unreported intronic variant in DMD and reduced dystrophin staining in the muscle biopsy. This novel DMD variant allele, c.9649+4A>T that was located in a splice donor site within intron 66. Sanger sequencing analysis from maternal DNA showed the presence of both variant c.9649+4A>T and wild-type (WT) DMD alleles. Different computational tools suggested that this nucleotide change might affect splicing through a WT donor site disruption, occurring in an evolutionarily conserved region. Indeed, we observed that this novel variant, could explain the reduced dystrophin protein levels and discontinuous sarcolemmal staining in muscle biopsy, which suggests that c.9649+4A>T allele may be re-classified as pathogenic in the future. Our data show that the c.9649+4A>T intronic sequence variant in the DMD gene may be associated with an IMD phenotype and our findings reinforce the importance of a more precise diagnosis combining muscle biopsy, molecular techniques and comprehensive in silico approaches in the clinical cases with negative results for conventional genetic analysis.

    Pathogenic germline variants in DMD gene
    GENETICS

, which encodes the

    well-known cytoskeletal protein named dystrophin
    GENETICS

, are associated with a wide range of

    dystrophinopathies disorders
    DIAGNOSIS

, such as

    Duchenne muscular dystrophy (DMD, severe form)
    DIAGNOSIS

,

    Becker muscular dystrophy (BMD, mild form)
    DIAGNOSIS

 and

    intermediate muscular dystrophy (IMD)
    DIAGNOSIS

.

    Muscle biopsy
    PARACLINICAL

,

    immunohistochemistry
    PARACLINICAL

,

    molecular (multiplex ligation-dependent probe amplification (MLPA)/next-generation sequencing (NGS) and Sanger methods) and in silico analyses
    PARACLINICAL

 were performed in order to identify

    alterations in DMD gene and protein
    GENETICS

 in a patient with a clinical manifestation and with

    high creatine kinase levels
    BIOCHEMICAL

. Herein, we described a

    previously unreported intronic variant in DMD
    GENETICS

 and

    reduced dystrophin staining in the muscle biopsy
    SYMPTOMS

. This

    novel DMD variant allele, c.9649+4A>T that was located in a splice donor site within intron 66
    GENETICS

.

    Sanger sequencing analysis from maternal DNA
    PARACLINICAL

 showed the

    presence of both variant c.9649+4A>T and wild-type (WT) DMD alleles
    GENETICS

. Different computational tools suggested that this

    nucleotide change might affect splicing through a WT donor site disruption, occurring in an evolutionarily conserved region
    GENETICS

. Indeed, we observed that this novel variant, could explain the

    reduced dystrophin protein levels
    BIOCHEMICAL

 and

    discontinuous sarcolemmal staining in muscle biopsy
    SYMPTOMS

, which suggests that

    c.9649+4A>T allele
    GENETICS

 may be re-classified as pathogenic in the future. Our data show that the

    c.9649+4A>T intronic sequence variant in the DMD gene
    GENETICS

 may be associated with an

    IMD
    DIAGNOSIS

 phenotype and our findings reinforce the importance of a more precise diagnosis combining

    muscle biopsy
    PARACLINICAL

,

    molecular techniques
    PARACLINICAL

 and comprehensive in silico approaches in the clinical cases with

    negative results for conventional genetic analysis
    NEG_FINDINGS

.

high creatine kinase levels
reduced dystrophin protein levels


Acute Chest Pain in Duchenne Muscular Dystrophy Patient With Anomalous Coronary Artery: An Etiologic Conundrum.

A 14-year-old with Duchenne muscular dystrophy (DMD) developed chest pain with ST-segment elevation, elevated serum troponin, and progressive ventricular dysfunction. Multimodality imaging showed an anomalous right coronary artery from the left sinus of Valsalva with intramural course, but further diagnostic testing led to the diagnosis of acute presentation of DMD-associated cardiomyopathy. (Level of Difficulty: Beginner.).

A

    14-year-old
    AGE

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 developed

    chest pain
    SYMPTOMS

 with

    ST-segment elevation
    SYMPTOMS

,

    elevated serum troponin
    BIOCHEMICAL

, and

    progressive ventricular dysfunction
    SYMPTOMS

.

    Multimodality imaging
    PARACLINICAL

 showed an

    anomalous right coronary artery from the left sinus of Valsalva with intramural course
    SYMPTOMS

, but further diagnostic testing led to the diagnosis of

    acute presentation of DMD-associated cardiomyopathy
    DIAGNOSIS

. (Level of Difficulty: Beginner.).