Search

Hypertrophic cardiomyopathy is a disease characterized by left ventricular hypertrophy (with or without right ventricular hypertrophy) not explained by loading conditions, the origin of which may be genetic and whose phenotypic expression is highly variable. The novelties in terms of diagnosis, clinical development, and management have been the subject of an update of the recommendations of the European Society of Cardiology (ESC).

Donohue syndrome or leprechaunism is a severe congenital insulin-resistance syndrome. It is characterized by intra-uterine and neonatal growth retardation, typical dysmorphic features, and metabolic abnormalities with hyperinsulinism and hyperandrogenism. Problems in energy metabolism and loss of glucose homeostasis are responsible for early death in the first year of life. We describe a case with a novel homozygote mutation in the insulin receptor gene. This patient had hypertrophic cardiomyopathy with heart failure and bronchial compression leading to clinical deterioration over 5 days and subsequently death. A treatment with recombinant IGF-1 was tried without efficacy., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Hypertrophic cardiomyopathy is the most common genetic heart disease. It is caused by a variety of mutations in genes encoding sarcomeric proteins. Clinical presentation is heterogeneous just as the clinical course, ranging from asymptomatic forms to sudden cardiac death in the young. The latter is an unpredictable, fortunately rather uncommon, complication with no reliable preventive treatment. The complexity lies in the identification of high risk patients who could benefit from an implantable cardioverter-defibrillator in primary prevention. Symptomatic patients presenting left ventricular outflow tract obstruction despite optimal medical treatment may undergo surgical septal myectomy or percutaneous alcohol septal ablation.

Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency, leads to an accumulation of globotriaosylceramide resulting in a multisystemic disorder. The initial manifestations of the disease are not specific, leading to a delayed diagnosis. We report a patient in whom the diagnosis was obtained by family screening and the confrontation of clinical signs. We also present a 4 year follow-up under enzyme replacement therapy (agalsidase β, 1 mg/kg/14 days)., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Primary hypertrophic cardiomyopathy is a relatively frequent disease (1/500) which results from a mutation in a gene encoding a sarcomeric protein. In a series of 184 cases, nearly half (46 %) were secondary to a mutation in one of the 4 following genes : MYBPC3, MYH7, TNNI3, TNNT2. In Fabry disease, an exclusive or nearly exclusive cardiac expression is possible and referred to as "cardiac variant". The hypertrophic cardiomyopathy of Fabry disease is usually unspecific. Two series reported a prevalence of Fabry disease of about 6% among male cases. An Italian series of 34 female cases with hypertrophic cardiomyopathy demonstrated that it was feasible to diagnose Fabry disease in females by screening for specific lesions in myocardial biopsies. We detected a patient who initially presented with a common hypertrophic cardiomyopathy except that his ECG showed depression of ST segment and inversion of T wave in leads D1, VL and in precordial leads. The family history revealed several affected relatives and female carriers. In conclusion, an isolated common hypertrophic cardiomyopathy may be secondary to Fabry disease. Male patients should be screened systemically for enzyme defect except in cases of father-to-son transmission. In females, an affected male relative should be searched for screening or the GLA gene should be sequenced. It is important to think about a putative Fabry disease in cases with hypertrophic cardiomyopathy not associated with any obvious cause., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Diffuse arterial calcified elastopathy is a very rare and little known hereditary disease, characterized by diffuse calcifications of the arterial wall. It seems common in North Africa and in the Caucasian region. Its incidence appears to be underestimated in Morocco. Clinical pattern is dominated by renovascular hypertension often associated with symptoms of heart failure. Risk of sudden death from myocardial infarction is particularly important. Thus, the diagnosis of diffuse arterial calcified elastopathy must always be suspected in front of an apparently unexplained heart failure or renovascular hypertension occurring in an infant. We report a case of diffuse arterial calcified elastopathy discovered in a neonatal intensive care unit, during management of a cardiogenic shock in a 3-months old infant. This observation demonstrates the importance of systematic measurement of the arterial tension, family screening and the impact of the ultrasound in the detection of vascular calcifications. Treatment remains essentially symptomatic.

Sudden cardiac death is one of the most prevalent cause of death in developed countries. Its aetiology varies according to the age. Some cardiac diseases may explain sudden death with minimal or no anatomic findings. However, many cardiac diseases, as for example channelopathies and hypertrophic cardiomyopathy have a genetic basis. Therefore genetic analyses (molecular autopsy) are becoming a useful tool in forensic medicine to identify the cause of sudden cardiac death and to improve the early diagnosis of asymptomatic carriers among relatives.

Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.

Hypertrophic cardiomyopathy (CMH) is characterised by hypertrophy of the left ventricle, typically predominantly asymmetric on the interventricular septum. The dreaded complication of the disease is sudden death, especially on physical exertion, and this can constitute the first symptom of the disease. Classified as primary or idiopathic for a long time, there have been considerable recent advances in the molecular genetics which have allowed the physiopathology of the disease to be unveiled. There is great genetic heterogeneity but the different genes have in common a coding for sarcomere proteins. Functional studies suggest that the mutations entail a primary alteration of sarcomere function, with secondary and compensatory hypertrophy. The genetic data equally offer the opportunity to re-evaluate the natural history and the clinical spectrum of the disease. A better understanding of the disease, coming from these molecular data, has allowed a great improvement in the relevance of the information given to patients and their relatives during genetic counselling consultations. The performance of a genetic test with a medical aim can equally be discussed in certain specific situations.

Hypertrophic cardiomyopathy (HCM) is a rare, often familial condition, which may be complicated by syncope, atrial or ventricular arrhythmias and episodes of cardiac failure. This genetic disease affects young people and may be observed in women wishing for a pregnancy. The duration and outcome of such pregnancies has not been extensively studied. The authors undertook a retrospective study by questionnaire to compare the pregnancies of 41 women with HCM, a total of 150 pregnancies, with those of 39 unaffected women from the same families: a total of 132 pregnancies. None of the women died, there were no hospital admission for cardiac causes and there was no aggravation of functional status (31% of women with HCM had symptoms before pregnancy compared with 27% during pregnancy). The foetal prognosis was good with no increase in prematurity or neonatal crises. Only the women with symptoms before pregnancy had an increased risk of foetal prematurity compared with healthy women (18% versus 5%). These results indicate the good tolerance of pregnancy of women with HCM and should lead to a revision of systematic medical contra-indication of pregnancy in these patients.

Heart failure is a major health problem and is associated with a high mortality and morbidity. Recently, the role of the genetic background in the onset and the development of the disease has been evidenced in both heart failure with and without systolic dysfunction, and in familial and non familial forms of this condition. Several genes and loci are know identified as responsible for dilated cardiomyopathies and for hypertrophic cardiomyopathies in familial and monogenic forms. Susceptibility genes and modifier genes are also studied in nonfamilial forms of dilated cardiomyopathies. The analysis of genetic factors that predispose to heart failure looks promising. It should allow to better understand the underlying mechanisms that promote the development and the progression of the disease, to identify subjects at risk for the disease who would benefit of an early medical management and promote the development of pharmacogenetics.

Hypertrophic cardiomyopathy (HCM) is defined as primary hypertrophy of the heart muscle, usually the left ventricle which is not dilated. HCM is a relatively common disease with a prevalence estimated at about 1 in 500. It is a complex disease with relatively stereotypical anatomical features but a very variable clinical presentation with a major risk of complication. All forms may be observed from almost asymptomatic hypertrophy to severe familial forms with multiple cases of sudden death. Over the last few years, molecular studies of the genetic abnormalities responsible for HCM have improved our understanding of the clinical variability of this disease. Schematically, HCM is caused by mutation of one of 4 genes which code the proteins of the sarcomere: the gene of the heavy chain of beta-myosin, the gene of cardiac T-troponin, the gene of alpha-tropomyosin and the gene of protein C linked to cardiac myosin. The main problem for clinicians is not making the diagnosis, which is relatively simple by echocardiography, but to assess the risk of complications, especially in adolescents and young adults. Patients over 40 to 45 years of age pose fewer problems as their disease is generally associated with a better prognosis since they have already survived to that age. There are many prognostic factors of sudden death, a reflection of the multifactorial character of sudden death in this disease. Four major risk factors have been identified: a family history of sudden death, abnormal blood pressure changes on exercise, a history of syncope and non-sustained ventricular tachycardia on 24 or 48-hour Holter monitoring. In children and adolescents, only the first three factors may be used, knowing that syncope, though rare, carries a very poor prognosis. On the other hand, in adults up to 40, all 4 factors are valid. Unfortunately, their positive predictive value is relatively poor, all the patients with one of these risk factors not automatically experiencing sudden death. On the other hand, their negative predictive value is excellent. Therefore, a patient with none of these factors has an excellent prognosis and should be allowed to lead a normal life. The risk is considered to be high when 2 or 3 of the factors are associated, theoretically justifying aggressive management (amiodarone? defibrillator?). Finally, there is no established management protocol in cases with a single risk factor. The discovery of mutations causing HCM will probably open up new methods of assessing the risk of sudden death in this disease. It would seem to be possible to assess the impact of the genotype on prognosis. However, this "genetic stratification" remains the realm of top research teams and is not yet accessible routinely in clinical practice.

In order to assess the value of Doppler tissue imaging (DTI) in the differentiation of physiological hypertrophy of athletes from primary hypertrophic cardiomyopathy (HCM), the authors compared a group of 20 normal, non-athletic subjects, a group of 43 competitive athletes and a group of 20 patients with mild HCM. In addition to the conventional echocardiographic criteria, the velocity of wall motion at the endocardium and epicardium of the interventricular septum and the posterior wall as well as their gradients, were measured throughout the cardiac cycle. No significant difference was observed between normal subjects and the athletes with respect to velocities and the gradients of velocity. Early diastolic velocities of the posterior wall and interventricular septum were significantly lower than those of normal subjects and athletes. The systolic and early diastolic gradients of velocity of the posterior wall were significantly lower in HCM compared with the normal subjects and athletes. The gradient of velocity between the endocardium and epicardium of the interventricular septum was significantly lower in HCM compared with normal subjects in early diastole and with athletes in systole and early diastole. The best Doppler tissue imaging parameter to differentiate pathological hypertrophy of HCM from physiological hypertrophy of athletes was analysis of the gradient of velocity in early diastole of the posterior wall. A value of 0.7 sec-1 differentiated HCM with a sensitivity of 89%, a specificity of 95% and a diagnostic accuracy of 94%. Doppler tissue imaging is a more sensitive and specific technique than conventional Doppler echocardiography for detecting moderate forms of HCM.

Familial hypertrophic cardiomyopathy is a disease with very heterogeneous genetic characteristics, both at the intergenic level (7 genes have been identified and some of them are still unknown) and intragenic level (more than 100 mutations have been identified). This genetic heterogeneity at least partly explains the clinical heterogeneity, expressed in terms of the degree of left ventricular hypertrophy and the inherent risk related to the disease (sudden death and/or heart failure). However, the understanding of phenotype/genotype relationships of this disease is only in the very early stages. So-called "modifier" genes are probably involved to modify the clinical profile of the disease. Many healthy carriers have been identified, but their outcome is unknown at the present time. The molecular genetics of HCM allows reevaluation of the classical clinical criteria. In the future, it would be desirable to establish specialized units for predictive and antenatal diagnosis, composed of cardiologists specialized in the disease, geneticists and psychologists in order to consider all clinical, ethical, and psychological aspects of this disease. Hopefully, this new approach to cardiology will be able to establish a more accurate risk profile for exposed subjects and guide treatment options.

Cardiomyopathies, and more specifically hypertrophic cardiomyopathy, have opened the route to what is now called genetic cardiology. Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left and/or right ventricular hypertrophy, and disorganisation of tissular architecture. Approximately 60% of HCM are transmitted as an autosomal dominant trait. The clinical aspects of HCM vary markedly, and several morphological variants were described, depending on the localization of hypertrophy. This pathology is often complicated by cardiac failure, but the major risk is sudden death, and the predictive factors are presently very unrefined. Several pathogenic hypotheses were forwarded in the past, and one surprising result of genetic analyses is that none of these hypotheses was confirmed. Four disease genes were identified, and they encode sarcomeric proteins, cardiac myosin heavy chain, troponin T, tropomyosin and cardiac myosin binding protein C. To this high intergenic heterogeneity is associated a high intragenic heterogeneity. A major fall out of these genetic findings is the recent discovery of adult healthy carriers, around 30% in our experience. Genetype/phenotype relationships are being performed, and this is the first approach to a prognostic evaluation based on genetic localisation. The work on hypertrophic cardiomyopathy is currently being used as a model to analyse dilated cardiomyopathies, characterized by dilatation and impaired contraction of the left or both ventricles. The mode of inheritance of these forms of cardiomyopathies is complex. Five families with an autosomal inheritance were analyzed since two years, the loci were found, but the disease genes are not identified yet. Identification of patients at high risk and early treatment or prevention are the current goals.

Introduction: A survey of all French Centres performing heart and heart lung transplant provided an exhaustive registry of pregnancy after transplantation., Material and Methods: A questionnaire was sent to 36 Centres. Anonymous reports of transplantation and subsequent pregnancies which occurred between 1984 and 1994 were analyzed., Results: Among 1290 heart and 120 heart lung transplantations performed during the study period 10 pregnancies were reported in 9 patients (6 after heart transplantation and 3 heart-lung transplantation) who gave birth to 11 neonates. The interval between the transplantation and the pregnancy is 23.1 months (range: 10-39). High blood pressure complicated nine pregnancies and severe preeclampsia occurred in two cases. Immunosuppressive therapy was i) Cyclosporine alone (n = 1), ii) i with corticosteroid therapy (n = 7), iii) ii with azathioprine (n = 2). One patient developed Kaposi sarcoma of the cervix. Delivery at 35 (27-39) weeks' gestation was by caesarean section in 50% of the cases. Mean birthweight was 1990 gm (range: 700-2880) and 50% of the neonates were below the tenth centile. One child developed cardiomyopathy as diagnosed in her mother and another one was diagnosed with congenital hepatitis B by absence of prophylaxis at birth. All the patients are alive at this time.

Although physiologists have recognised for many years that cardiac performance is based on two functions, systolic and diastolic, it has only been in the last 15 years that clinicians have acknowledged the essentiel role of diastole in the physiopathology of cardiac disease. Many studies have shown that left ventricular diastolic dysfunction resulting from abnormal active relaxation or changes in passive visco-elastic properties of the myocardium modulating its rigidity were responsible for decreased distensibility of the ventricle and an increase in its filling pressures. Therefore, the symptoms of the majority of patients with cardiomyopathy are due, more or less, to diastolic dysfunction. This is particularly the case in hypertrophic cardiomyopathy, most case of which have diastolic dysfunction secondary to an often asymetric distribution of the hypertrophy, to the disorganisation of the myocardiofibres and to interstitial fibrosis. With respect to advanced forms of restrictive cardiomyopathy, as their clinical and haemodynamic characteristics resembling constrictive pericarditis show, they demonstrate caricatural diastolic dysfunction. Finally, although the main abnormality in dilated cardiomyopathies is poor contractility, a decrease in ventricular compliance is constantly observed.

Considerable progress has been accomplished in the understanding of the genetics of familial hypertrophic cardiomyopathy over the last five years. This is a monogenic autosomal dominant condition with much inter- and intragenic variability. Four morbid genes coding for the contractile proteins have been identified: the heavy beta chain of cardiac myosin (14q11), cardiac troponin T (1q3), alpha tropomyosin (15q2), and myosin binding cardiac C protein (11p13-q-13). In addition, other genetic localisations not yet identified are certain. Moreover, many mutations have been reported in the already identified genes. The principal clinical perspectives ot this research lie in the analysis of the relationships between phenotype (clinical expression) and genotype with respect to prognosis, the severity and morphology of the hypertrophic process, the reevaluation of our diagnostic criteria and the long-term follow-up of the many healthy carriers in the identified families. The genetic heterogeneity of the disease is a limiting factor in genetic counselling and there are ethical problems related to the absence of effective treatment.

Hypertrophic cardiomyopathy may be secondary to a mutation in the cardiac beta myosin heavy chain (14q11-q12), alpha tropomyosin (15q22), troponin T (1q32), protein C gene (11p11-q13) or in a non yet mapped gene. A X-linked dilated cardiomyopathy may be due to a mutation in the dystrophin gene (Xp21). The long QT syndrome may be secondary to a mutation in a potassium channel (7q35-36), an alpha subunit of the sodium channel gene (3p21) or in genes not yet identified (11p15.5, 4q25-q27). Marfan syndrome is associated to mutations in the fibrillin 1 gene (15q21.1) and a Marfan-like syndrome with not ocular anomalies was mapped to 3p24. Patients with Williams-Beuren syndrome have microdeletions in 7q11, whereas in the supravalvular aortic stenosis, the elastin gene which maps to the same region, is mutated. In Di George and Shprintzen syndromes but not in conotruncal malformations, microdeletions in 22q11 are observed. Heterotaxia can be transmitted by 3 types of mendelian inheritance (Xq24-q27.1). Finally, other diseases were mapped: Noonan and Holt-Oram syndromes (12q), isolated conduction blocks (19q13.3), arrhythmogenic right ventricular cardiomyopathy (14q23-q24), total anomalous pulmonary venous return (4p13-q12) and Osler-Weber-Rendu (9q33-q34.1, 3p22 and 12q1). In the near future, these incoming data will deeply modify the cardiovascular field.

Hypertrophic cardiomyopathy is an uncommon disease, important to recognize. Family screening is mandatory, with physical examination, EKG and echocardiography. Genetic diagnosis will modify our approach in a near future. The different treatments are described: drugs, surgery, pacing. The role of the general practitioner is complementary to the cardiologist's. His task is especially important in the first step of the diagnosis.

Hypertrophic cardiomyopathy is usually familial with an autosomal dominant mode of transmission. The condition is genetically heterogeneous. The first defective gene to be described was that of the beta heavy chain of cardiac myosin (beta-MHC, chromosome 14 q11-q12) where over 20 different localised false sense mutations and a hot point of mutation in exon 13 have been reported. This locus seems to be implicated in 30% of families studied. Systematic screening of the genome has led to the detection of new sites on chromosomes 1, 11 and 15. No gene has yet been identified in these three new loci. For all new families, present strategy consists in determining the locus responsible for the disease by linkage analysis. For beta-MHC locus a panel of several markers (the two MYO I and MYO II microsatellites of the beta-MHC gene and two new AFN microsatellites) has been established which allows accurate detection of whether the haplotype cosegregates with the disease, even in relatively small families. It is then necessary to define the mutation by PCR amplification of the exons followed by electrophoresis on Hydrolink-MDE gels and sequencing of the mutant exons. Some subjects are genotypically affected but phenotypically normal and it seems the penetrance varies with the type of mutation. Analysis of the genotype/phenotype relationship should be continued in order to improve our knowledge of the consequences of each mutation. The genotype diagnosis is therefore complex and cannot be undertaken at present of the examination of the propositus. Whole families must be sampled.(ABSTRACT TRUNCATED AT 250 WORDS)

An echocardiographic Study of 322 adults (age: 40 +/- 16 years), belonging to 20 families with hypertrophic cardiomyopathy (HCM), was undertaken. Affected subjects had a LV diastolic wall thickness > 13 mm. The patients were classified according to the distribution of left ventricular hypertrophy (LVH) and by Maron's classification: 189 subjects were normal, 127 were affected and 6 could not been classified. By Maron's classification: 3% were type I, 33% were type II, 58% were type III and 6% were type IV. LVH was asymmetrical in 95% of cases (septum/posterior wall ratio > 1.3). The familial distribution of LVH of the 4 families in which HCM was genetically related to different loci (chromosome 11, 14 exon 13, 14 exon 8, fifth locus); the LVH was analysed from two short axis LV parasternal views and each plane was divided into 5 segments. The distribution of LVH was said to be identical between two first degree relations when all the same segments were affected, similar when they differed by only 1 or 2 segments and different when they differed by 3 or more segments. In the 26 pairs studied, LVH was identical in 2/26 (8%), similar in 11/26 (42%) and different in 13/26 (50%). Familial HCM usually gives rise to asymmetrical LVH affecting the septum and free wall. An identical distribution in 50% of affected first degree relatives.

Hypertrophic cardiomyopathy is familial in about 50% of cases and is transmitted in the autosomal dominant mode. The first morbid gene implicated in the disease was the gene coding the beta myosin heavy chain (beta MHC) on chromosome 14. However, only 30% of families have this genetic abnormality. Recently, three new loci have been identified on chromosomes 1q3, 11p13-q13 and 15q2. In order to determine whether other genes could be implicated in the disease a linkage analysis study was performed in a West Indian family. The method is based on the analysis of the distribution of the disease in the family and the microsatellite markers. The microsatellites used were those which recognised the 4 loci previously mentioned and 4 new markers situated and arranged with respect to known microsatellites. The results show that in the family studied, the disease did not concord with the markers of the beta MHC gene or with those recognising the loci on chromosomes 1q3, 11p13-q13 and 15q2. There is, therefore, a fifth gene implicated in familial HCM. The heterogeneity of the disease seems even greater than originally thought.

A French multicentre study of hypertrophic cardiomyopathy has recruited 260 subjects belonging to 18 families. At least 3 persons from each family included had a hypertrophic cardiomyopathy. A Doppler echocardiographic examination was performed in all members of these 18 families. The diagnosis of hypertrophic cardiomyopathy was based on M mode and/or 2D observations of parietal hypertrophy: wall thickness over 13 mm. Asymmetrical forms were distinguished from symmetrical forms by a septum/posterior wall ratio of over 1.3 in M mode or 2D study. The patients had an average age of 40 +/- 18 years, 127 were men and 133 women. One hundred and sixty eight were considered to be normal, 87 had hypertrophic cardiomyopathy and 5 were border line. The maximal diastolic wall thickness on M mode recording of pathological cases was 19.2 +/- 4.8 mm compared with 9.5 +/- 1.9 mm in healthy subjects (p < 0.001). The septum/posterior wall ratio was 1.8 +/- 0.62 in pathological cases and 1.1 +/- 0.8 in normal ones (p < 0.001). Eighty five per cent of the cardiomyopathic cases were asymmetrical (74/87) and only 15% were considered to be symmetrical (13/87) on M mode study whereas 5% were concentric on 2D echocardiography. By Maron's classification, type I hypertrophy was observed in 6% of cases (4/64), type II in 30% (19/64), type III in 58% (37/64), and type IV in 6% (4/64). Signs of obstruction were looked for and systolic anterior motion of the mitral valve was observed in 52% of pathological cases (45/86) and mid-systolic aortic valve closure in 30% (25/83).(ABSTRACT TRUNCATED AT 250 WORDS)

The morphological features, mode of presentation and physiopathology of hypertrophic cardiomyopathy (HCM) are variable. Autosomal dominant seems to be the usual mode of transmission but with variable presentation. From the anatomical point of view, the hypertrophy is asymmetrical with septal predominance. The main histological features are myocytic architectural disorganisation, fibrosis and abnormal coronary arteries of small diameter. Ventricular hyperkinesis is usually present and sometimes associated with outflow obstruction, the physiological role and mechanisms of which are still not fully understood. On the other hand, abnormal diastolic function is frequently observed, and, quite independently of disease of the epicardial coronary arteries, ischaemic phenomena may occur. Although the biological substrate of HCM is unknown, abnormalities of the adrenergic system and transmembrane calcium flux probably play a part in the expression of the disease.

This report concerns a family in which several members presented an involvement of skeletal and velo-pharyngeal muscles, associated with hypertrophic cardiomyopathy, respiratory disturbances and lens opacities. The mode of transmission is autosomal dominant. The E.M.G. showed neither spontaneous activity nor myotonic discharges. In two patients, the muscle biopsies showed identical changes. By light microscopy it was seen that in numerous type I fibres, the intermyofibrillar network was "rubbed out" and this occurred along with splitting of such fibres. Electron microscopy revealed an intrasarcoplasmic accumulation of an electron-dense granulo-filamentous material: in some areas it formed a mesh of threads around the myofibrils and in others it was disposed regularly in small stacks facing the Z lines. Continuity or structural similarity of this material and the Z lines was not observed; its relationship with the dense strips of leptofibrils is suggested.

Fourteen cases of apical hypertrophic cardiomyopathy (i.e. hypertrophy localized to the distal half of the left ventricular wall) are reported. There were 12 men and 2 women aged from 21 to 84 years. Only one of the patients presented, at first consultation, with severe functional symptoms, namely stage IV dyspnoea. ECG tracings were always abnormal, but the classical giant T waves were found in only 7 patients. In the 9 patients who had cardiac catheterization the left ventricular end-diastolic pressure was raised, and angiography showed an "ace of spades" diastolic image of the left ventricle with systolic obliteration of its tip. The distribution of parietal hypertrophy was best studied by two-dimensional echocardiography: the left ventricular apex was affected alone in 7 patients and concomitantly with the adjacent segments of the left or right ventricle in the other 7 patients. A family study showed that 3 patients had a descendant with obstructive cardiomyopathy. At a 4.6 years' follow-up the course of the disease was usually favourable. Apical hypertrophic cardiomyopathy is not a particular entity but one of different possible forms of hypertrophic cardiomyopathy. It seems to be benign in most cases.

An unusual form of familial myocardiopathy is reported. The disease affected siblings entering adulthood and presented as subclinical skeletal muscle and patent cardiac muscle lesions. Quadriceps muscle biopsy performed in a young man who subsequently died of cardial failure revealed excessive lysosomal glycogen storage, as in type II glycogenosis, but biochemistry showed normal enzymatic activity. In a sister with hypertrophic myocardiopathy only leucocytes were examined; they also showed normal enzymatic activity. Other clinical manifestations of this form of familial myocardiopathy are hypoglycaemia and moderate skeletal muscle involvement. At histology, the image is that of Pompe's disease, but the acid maltase level is normal. The condition seems to be transmitted as an autosomal dominant trait.

Two related cases are reported, those of two sisters aged 7 and 13, who had an aortic subvalvular stenosis in the form of a fibro-muscular channel, associated with mitral incompetence, a triangular facies with a pointed chin, pinched lips, a divergent squint, hypertelorism, a mask-like face, normal intelligence, and a peripheral muscular disorder with arthrogriposis. The description of such a combination of malformations is original, and this is discussed.

Hypertrophic myocardiopathy with obstruction (HOMC) is a disease of unknown aetiology with a high familial incidence. This study was undertaken to determine its relationship to the HLA system, as proved in a number of other conditions. The clinical suspicion of HOMC was confirmed in all cases by echocardiography. In addition, 4 patients were also catheterised, confirming the presence of an intraventricular pressure gradient. One patient was investigated after surgery. None of the patients was hypertensive. In two cases, a positive family history of HOMC confirmed the hereditary nature of the condition. The HLA-A and B grouping was performed by the micro-lymphocytotoxic technique. The HLA-DRW was carried out with B lymphocytes separated either by column filtration or by rosetting on a Ficoll gradient. We did not find a statistically significant prevalence of any of the antigens tested on the A, B on DRW loci. Our results were compared with previously published data. They support the findings of Bloch et al. in a genetically comparable study population (HLA A and B only) but contradict those of Matsumori (oriental population). We were unable to demonstrate a liaison between antigens of the HLA system and HOMC. However, as was shown in our study, HLA grouping is valuable in familial forms of HOMC (mechanism of transmission, detection of clinically latent forms).

The treatment of hypertrophic cardiomyopathy is first and foremost symptomatic, its aim being to counteract dyspnea, angina pectoris, syncopes and lipothymias, palpitations. In therapy, use is made of beta-blockers, propranolol in particular at moderate or high doses, which are often efficacious but readily cause muscular asthenia. Calcium antagonists, especially verapamil, are a therapeutic alternative, often more efficacious but exposing the patient to the risks of iatrogenic effects which are sometimes serious and may even be fatal. Surgical myomectomy is another alternative, the functional results of which are remarkable, more often than not, but the mortality at surgery, although declining progressively, is not negligible and leads to this approach being used only in cases not responding to medical treatment as when infra-aortic septal hypertrophy is accompanied by an "obstruction". The second type of therapeutic approach is the treatment and prevention of rhythmic disorders which are an integral part of the risk of sudden death. Reduction of auricular fibrillation must play a role in the prevention of thrombo-embolic disease. Ventricular arrhythmias, especially sustained attacks of ventricular tachycardia systematically detected by ambulant ECG, ought to be prevented by anti-arrhythmics: beta-blockers, in combination or not with anti-arrhythmics of class I, amiodarone, propafenone, etc.

33 patients with hypertrophic cardiomyopathy were followed for a mean duration of 48 months. 29 of them were reviewed; 6 had died, including 4 with a familial form belonging to two different families. No cases of sudden death were observed. The mortality rate was 4 p. cent at 1 year, 11 p. cent at two years and 21 p. cent at 5 years. The clinical course was marked by a functional deterioration in one-third of cases and, on echocardiography, by an increase in the diastolic diameter of the left ventricle and in the thickness of the septum, independent of the clinical course. Subjects from "high risk" families have a very poor prognosis (4 deaths out of 7 patients at an average age of 25). These families present major conductive disturbances on the electrocardiogram and a very marked parietal hypertrophy on the echocardiogram. No other prognosis factor independent of the familial aspect was revealed.

We describe a family in which two generations are affected: two brothers and one of their maternal uncles. One of their two half-sisters (same mother) is also suspected of having the same cardiopathy. This observation confirms the autosomal dominant transmission of the disease and shows its variable expressivity in the family under study.