Schwartz-Jampel syndrome (SJS, MIM 255800), also known as chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia, skeletal abnormalities and facial ...dysmorphism. Using homozygosity mapping, we localized the SJS locus to chromosome 1p34-p36.1 in a 8 cM interval flanked by markers D1S199 and D1S234. Families of different ethnic backgrounds (Tunisia and South Africa) showed genetic linkage to the same locus. Moreover, one Algerian family also demonstrated evidence of genetic linkage to 1p34-p36.1. Taken altogether, our results suggest genetic homogeneity, at least in the group of families analyzed.
The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreich's ataxia and 15 patients with ...Friedreich's ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreich's ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreich's ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreich's ataxia and central distal axonopathy in Friedreich's ataxia phenotype with selective vitamin E deficiency.
Autosomal dominant cerebellar ataxias (ADCA) type 1 are a clinically and genetically heterogeneous group of neurodegenerative disorders. We report a large Tunisian ADCA type 1 family in which 17 ...patients (mean age at onset +/- SD = 35.6 +/- 15.3 years) were examined. There was mean anticipation of 10.3 +/- 15.4 years in this family; anticipation was greater in paternal (28 +/- 8.2 years) than in maternal (2.7 +/- 10.9 years) transmission. Linkage analysis performed with microsatellite markers linked to the spinal cerebellar ataxia 1 (SCA1) locus on chromosome 6p and the SCA2 locus on chromosome 12q excluded linkage to SCA1, but there was close linkage with marker D12S105 (Zmax = 2.51 at theta = 0.00). This result was confirmed by multipoint analysis, which generated a maximal lod score of 3.46 at this locus. Multipoint analysis and haplotype reconstruction reduced the interval containing the SCA2 locus to 6.4 cM, a narrowing of the 35-cM interval in a previously described Cuban SCA2 family with a clinical picture similar to that of our family, including a high frequency of postural and action tremor.
Schwartz-Jampel syndrome (SJS), or chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia resulting in a particular, recognizable facies and ...osteoarticular abnormalities. Some of us have recently shown genetic linkage of SJS to a locus on 1p34-p36.1 in five families. Here, we show by homozygosity mapping and segregation analysis that eight new families are most likely linked to the SJS locus on chromosome 1, confirming the localization of SJS to chromosome 1p and suggesting genetic homogeneity. Recombination events reduced the SJS locus from a genetic interval of 8 to 3 cM, which should facilitate the identification of the SJS gene. Low clinical variability was observed between the studied families, except for osteoarticular abnormalities. Since the severity and the location of osteoarticular abnormalities varied from one individual to another, even in the same families, other factors than the SJS gene itself, genetic or epigenetic, might contribute to the phenotype.
Objectives. To report clinical, pathological and genetic findings in a Tunisian kindred with autosomal recessive juvenile parkinsonism (AR-JP) linked to parkin gene.
Background. AR-JP has been mapped ...to chromosome 6q and is caused by several mutations of the parkin gene (Park 2). Pathological features in AR-JP are characterized by neuronal loss in substantia nigra (SN) without Lewy bodies (LB).
Patients and methods. Three affected siblings with juvenile Parkinson's disease were studied. Pathological examination of the brain was performed in one of them. Linkage studies and mutation analysis of the parkin gene were performed.
Results. Clinical picture was characterized by the association of rest tremor, bradykinesia and rigidity. Parkinsonian signs markedly improved with levodopa treatment in the three siblings. Dystonia was observed in one patient and diurnal fluctuations of parkinsonian signs in another one. Linkage analysis showed homozygous haplotypes in patients as compared to unaffected individuals and mutation analysis of the parkin gene revealed a homozygous two-base AG deletion in exon 2 (101–102). Pathological examination of the brain in one patient showed marked loss of pigmented neurons with extraneuronal free melanin in the lateral and medial parts of the SN associated to a slight spongiosis and astrocytic gliosis. In the locus coeruleus, there was also loss of pigmented neurons without gliosis. No LB or neurofibrillary tangles were found neither by traditional nor by histo-immunological stainings.
Conclusion. This Tunisian kindred with AR-JP linked to a micro-deletion of the parkin gene shows clinical similarities with the previously reported Japanese and European families. Pathological features of this kindred are compared to what has been reported in AR-JP families linked to large exonic deletions of this gene.
Amyotrophic lateral sclerosis (ALS) usually presents as a sporadic disorder of motor neurons. However, familial forms of ALS have been described--autosomal dominant forms (ALS1, ALS3), clinically ...indistinguishable from the sporadic form, and autosomal recessive forms with early onset and slower progression of symptoms (ALS2). To localize the gene for one of the autosomal recessive forms of ALS, we applied linkage analysis to a large inbred family from Tunisia. A lod score maximum of Zmax = 8.2 at theta = 0.00 was obtained with marker D2S72 located on chromosome 2q33-q35. The fine mapping of this region suggested that the ALS2 locus lies in the 8 cM segment flanked by D2S155 and D2S115.
La cardiomyopathie du péripartum (CMPP) dont la pathogénie reste mal connue est caractérisée par une défaillance myocardique qui peut survenir durant le dernier mois de la grossesse et jusqu’à cinq ...mois après l’accouchement. L’objectif de cette revue est de détailler les mécanismes physiopathologiques, les manifestations cliniques, les moyens diagnostiques, aussi bien que la prise en charge thérapeutique et le pronostic de cette pathologie.
Nous avons fait une analyse de la littérature sur cette pathologie et nous avons recherché sur le Medline, PubMed et sur le Google la liste des articles pour des références appropriées.
La CMPP est une cardiomyopathie dilatée fréquente en Afrique noire. Sa physiopathologie semble être complexe et plusieurs hypothèses physiopathologiques ont été avancées : le rôle de l’inflammation, des infections virales et des mécanismes auto-immunes semble être prédominant. Ce diagnostic devrait être limité aux femmes en bonne santé qui se présentent pour une insuffisance cardiaque pouvant s’aggraver très rapidement. La confirmation diagnostique se fait par l’échographie cardiaque qui montre une cardiomyopathie dilatée survenant pendant le péripartum, avec une altération de la fonction ventriculaire gauche (fraction d’éjection <
45 %). Le traitement conventionnel repose sur l’utilisation des diurétiques, des vasodilatateurs et parfois de la digoxine. Les tonicardiaques seront utilisés chez les patients qui ne répondent pas aux traitements conventionnels. Dans les cas résistants, les immunoglobulines et/ou les immunosuppresseurs peuvent être utilisés. Le pronostic est fortement lié à la récupération de la fonction cardiaque. En se basant sur les données récentes, une grossesse ultérieure ne peut être autorisée que chez les patientes qui récupèrent une fonction cardiaque normale.
La CMPP est une forme rare mais grave de l’insuffisance cardiaque dont la pathogénie reste mal connue. Le pronostic est étroitement lié à la récupération complète de la fonction cardiaque.
Peripartum cardiomyopathy (PPCM) is a rare and life-threatening disease of unknown aetiology. The primary objective of this review was to analysed aetiopathogeneses, clinical presentation and diagnosis, as well as pharmacological, perioperative and intensive care management and prognosis of this pathology.
We undertook a systematic review of the literature using Medline, Google Scholar and PubMed searches.
Unlike other parts of the world in which cardiomyopathy are rare, dilated cardiomyopathy is a major cause of heart failure throughout Africa. Its aetiopathogenesis is still poorly understood, but recent evidence supports inflammation, viral infection and autoimmunity as the leading causative hypotheses. This diagnosis should be limited to previously healthy women who present with congestive heart failure (CHF) and decreased left ventricular systolic function in the last month of pregnancy or within 5 months after delivery. Recently, introduction of echocardiography has made diagnosis of PPCM easier and more accurate. Conventional treatment consists of diuretics, vasodilators, and sometimes digoxin and anticoagulants, usually in combination. Patients who fail to recover may require inotropic therapy. In resistant cases, newer therapeutic modalities such as immunomodulation, immunoglobulin and immunosuppression may be considered. Prognosis is highly related to reversal of ventricular dysfunction. Compared to historically higher mortality rates, recent reports describe better outcome, probably because of advances in medical care. Based on current information, future pregnancy is usually not recommended in patients who fail to recover normal heart function.
PPCM is a rare but serious form of cardiac failure affecting women in the last months of pregnancy or early puerperium. Its aetiopathogenesis is still poorly understood. Introduction of echocardiography has made diagnosis of PPCM easier and more accurate. Prognosis is highly related to reversal of ventricular dysfunction.
We report three brothers belonging to a consanguineous family and suffering from ataxia telangiectasia with severe early neurogenic amyotrophy. Pathological examination of the brain and spinal cord ...in one of them showed Purkinje cell loss with empty baskets and numerous axonal spheroids, dorsal column demyelination with astrocytic proliferation and severe anterior horn cell degeneration. We consider these pathological findings to be related to Louis-Bar disease. Anterior horn cell changes may be one of the early pathological features in ataxia telangiectasia.
To explore the myocardial perfusion by thallium-201 scintigraphy for patients with evidence of myocardial damage after scorpion envenomation.
Prospective study over 1-year period.
Medical intensive ...care unit of a university hospital (Sfax, Tunisia).
We have prospectively included six patients admitted for scorpion envenomation over a period of 1 year in the 22-bed intensive care unit (ICU) of our university hospital. The evidence of myocardial damage was confirmed by electrocardiography and echocardiography in all patients. Myocardial perfusion scintigraphy ((201)Tl scintigraphy) coupled with radionuclide ventriculography ((99m)Tc) was performed for all patients, occurring 32 h on average (range 12-72 h) after the sting.
Radionuclide ventriculography was abnormal in all cases; the abnormalities observed were similar to those observed by echocardiography. Moreover (201)Tl scintigraphy showed evidence of myocardial hypoperfusion in all cases. The myocardial hypoperfusion grade and localisation were more marked in the abnormal localisation shown by echocardiography and electrocardiography, compared to the normal wall. Repeated studies, obtained only in two patients within 6 and 15 days, respectively, showed considerable, but not complete, improvement of wall motion and myocardial perfusion. Segments with improved perfusion showed greatly improved regional wall motion.
This study confirms the evidence of myocardial hypoperfusion after severe scorpion envenomation.
Décrire les caractéristiques cliniques, détailler la prise en charge thérapeutique et dégager les éléments de mauvais pronostic maternel de la stéatose hépatique aiguë gravidique (SHAG) dans notre ...région.
Étude rétrospective sur une période de 11 ans (1993–2003). Nos critères d'inclusion sont : un diagnostic de stéatose hépatique aiguë gravidique confirmée histologiquement et/ou un tableau typique d'insuffisance hépatocellulaire survenant au cours du troisième trimestre de grossesse.
Nous avons colligé 22 patientes d'âge moyen de 30
±
5,4 ans. Les patientes étaient multipares dans 77,3 % des cas. Le terme moyen de grossesse a été de 36
±
2,76 SA (31 à 41 SA). Le fœtus était de sexe masculin dans 75 % des cas. La phase préictérique a été présente chez dix patientes (45,45 %), phase caractérisée par la présence de symptomatologie digestive (60 %). Quinze patientes ont développé un ictère soit à leur admission, soit durant leur évolution. À l'admission en réanimation le SAPS II moyen a été de 24,86
±
11,2 points. Sur le plan biologique, le bilan hépatique était perturbé dans 100 % des cas. Nous avons noté une cytolyse hépatique dans 91 % des cas, une tendance à l'hypoglycémie dans 86 % des cas, une hypoprotidémie dans 66,7 % des cas, et une CIVD dans 32 % des cas. Durant leur séjour en réanimation, 19 patientes (86,4 %) ont développé une ou plusieurs défaillances viscérales associées à l'atteinte hépatique. Après un séjour moyen de 7,5 jours, l'évolution a été marquée par la mort de sept patientes (31,8 %). Les éléments corrélés avec un mauvais pronostic sont : le retard de prise en charge, l'installation de l'ictère, l'encéphalopathie hépatique, l'état de choc et la détresse respiratoire.
La SHAG reste une pathologie grave. Le diagnostic à la phase préictérique et l'évacuation utérine précoce constituent les seuls éléments pouvant améliorer sensiblement son pronostic.
To report the clinical experience, biochemical findings, complications and maternal outcome in patients with acute fatty liver of pregnancy (AFLP).
Retrospective study over a period of 11 years (1993–2003). The diagnosis of AFLP was confirmed by liver biopsy in 15 women. However, in 7 women a medical committee that took into account clinical symptoms, and laboratory findings assessed the diagnosis.
Were included in this study, 22 women with a mean age of 30
±
5.4 years. Only 22.7% of cases were primigravid. The mean gestational age was 36
±
2.76 weeks (range 31–41 weeks). The fetus was a male infant in 75% of cases. Ten women were admitted in the hospital without jaundice. However 15 women had developed an icterus since their hospital admission or during ICU stay. The mean SAPS II on the ICU admission was of 24.86
±
11.2 points. Biological disturbances observed were mainly: liver cytolysis in 91% of cases, a trend to hypoglycaemia in 86%, a hypoprotidemia in 66.7% and CIVD in 32%. During their ICU stay, 19 women (86.4%) developed one or several organ failures associated to the hepatic failure and 18 women required blood transfusion. After an average stay of 7.5 days, evolution was marked by the death of seven patients (31.8%). Factors correlated with a poor prognosis were: the delay of medical consultation, the development of jaundice, the development of encephalopathy, respiratory or a circulatory failure.
AFLP is a rare but life-threatening complication. Furthermore AFLP shares features with other more common and less perilous illnesses. An early diagnosis and appropriate therapy of this pathology should improve the poor prognosis in our country.
