Bernard Echenne

Early Onset Collagen VI Myopathies: Genetic and Clinical Correlations

Mutations in the genes encoding the extracellular matrix protein collagen VI (ColVI) cause a spectrum of disorders with variable inheritance including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate phenotypes. We extensively characterized, at the clinical, cellular, and molecular levels, 49 patients with onset in the first 2 years of life to investigate genotype‐phenotype correlations.

Treatment of infantile spasms with intravenous gamma-globulins

In a prospective study, 23 children with infantile spasms received intravenous gammaglobulins in high doses. 19 patients present a West syndrome. 4 older patients were included in the study because infantile spasms had preceded their Lennox-Gastaut syndrome. None of the patients had recently undergone corticosteroid therapy. No effect was observed in 15 patients, while transitory clinical and/or electroencephalographic improvement was noted in 3. Complete normalization was obtained in the remaining 5 patients, of whom 4 had severe brain lesions. No correlation existed between the therapeutic results and immunological abnormalities, a deficiency in IgG subclasses in particular. On the whole, the therapeutic results were disappointing. But the existence of some cases in which spectacular electroencephalographic and/or clinical improvement was obtained leads us to suggest that IV gamma-globulins be used as auxiliary treatment in infantile spasms.

Congenital muscular dystrophy with cerebral white matter spongiosis

Two siblings affected with a slowly progressive congenital myopathy presented mental retardation, epilepsy and craniofacial dysmorphy. The cerebral necropsic study of one of these patients showed severe anomalies of the white matter, with spongiosis, astrogliosis and vascular hyperplasia, whereas a diffuse and marked hypodensity of white matter was observed at cerebral CT scan in the other patient. There were any lesion of cerebellar grey matter, heterotopy, micropolygyria or neuronal destruction. This syndrome seems to be an original variant of congenital neuromyopathy.

Congenital and infantile myotonic dystrophy

Myotonic dystrophy (DM) encompasses two gene defects, DM1 (myotonic dystrophy type 1) being currently the sole disorder leading to a childhood form of the disease. As consequence of the non coding unstable CTG repeat expansion mutation, DM1 presents as an extremely wide and diverse clinical continuum ranging from antenatal to late adult forms, the complexity of the disease being reinforced by multisystemic involvement. The congenital form appears as the most severe end of the phenotypic spectrum and may include marked neonatal hypotonia, respiratory failure, facial diplegia, contractures, and mental retardation. Brain involvement is the hallmark of childhood-onset DM1, distinguished by a normal neonatal period, with learning difficulties as the main presenting symptom, resulting from various degrees of mental delay, psychopathological manifestations, speech defects, hypersomnolence, and fatigue. In contrast, muscle weakness remains usually moderate in childhood, limited to facial weakness, ptosis, and dysarthria, until a decline from the second decade. Orthopedic manifestations including kyphoscoliosis and equinovarus may require surgery. Other organs involvement includes frequent abdominal symptoms, whereas endocrine disturbance is rare. Symptomatic cardiac arrhythmia, mainly exercise-induced, can be observed. While current treatment is mainly symptomatic, future clinical trials are expected following significant progress in pathophysiology and the recent development of molecular therapy approaches.

Vertebro-basilar arterial occlusion in childhood — Report of a case and review of the literature —

A 9-year-old boy developed ataxia, right transient hemiparesis, left transient hemichorea, dysarthria and swallowing difficulties with left velar paralysis following two transient episodes of vomiting, headache and dizziness. Angiography demonstrated an occlusion of the distal part of the basilar artery. Thirty-six previously reported cases of vertebro-basilar arterial occlusion in children were reviewed, with particular regard to possible etiologies.

Multicore Disease and Marfan’s Syndrome: A Case Report

A 16-year-old girl with a generalized nonprogressive motor weakness and clinical signs of Marfans syndrome is reported. A minicore disease was diagnosed after muscle biopsy. The association of Marfans syndrome with muscular dystrophies is discussed.

Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature

Background Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a multisystem inborn error of metabolism. Objectives To better characterise the natural history of PMM2-CDG. Methods Medical charts of 96 patients with PMM2-CDG (86 families, 41 males, 55 females) were retrospectively reviewed. Data on clinical, laboratory and molecular parameters at diagnosis were analysed. Follow-up data at last examination were reported for 25 patients. Results The patients were born between 1963 and 2011. Diagnosis of PMM2-CDG was made at a mean (SD) age of 6.8 (8.5) years. The presenting signs were mostly neurological (hypotonia, intellectual disability, cerebellar syndrome) and observed in almost all the patients. A total of 38 patients (14 males, 24 females) exhibited, in addition to neurological signs, visceral features including at least one of these: feeding difficulty requiring a nutritional support (n=23), cardiac features (n=20; pericarditis: 14, cardiac malformation: 9, cardiomyopathy: 2), hepato-gastrointestinal features (n=12; chronic diarrhoea: 7, protein-losing enteropathy: 1, ascites: 3, liver failure: 1, portal hypertension: 1), kidney features (n=4; nephrotic syndrome: 2, tubulopathy: 2) and hydrops fetalis (n=1). Twelve patients died at a mean age of 3.8 years (especially from pericarditis and other cardiac issues). Laboratory abnormalities mostly included elevated transaminases and abnormal coagulation parameters. High thyreostimulin levels, hypocholesterolemia, hypoalbuminemia and elevated transaminases were associated with the visceral phenotype. Besides the common Arg141His PMM2 variant harboured by half of the patients, 45 different variants were observed. Conclusions PMM2-CDG clinical phenotype is heterogeneous in terms of clinical course, with no clear division between neurological and visceral presentations.

Convulsions bénignes du nourrisson. Étude collaboratrice française

Resume Cette etude se propose de definir les caracteristiques cliniques et electroencephalographiques (EEG) des convulsions dites benignes du nourrisson. Patients et methodes Entre 1981 et 1994, 34 patients ont ete regroupes avec les criteres dinclusion suivants: convulsions non febriles, survenant chez un nourrisson entre lâge de 1 mois et 2 ans, sans antecedent neurologique, sans anomalies aux examens cliniques et paracliniques. et dont levolution neurodeveloppementale savere normale avec au moins 2 ans de recul. Resultats Ces 34 patients rassemblent 14 cas familiaux (crises identiques dans la famille), 11 cas non familiaux (sans aucun antecedent familial depilepsie) et neuf cas avec epilepsie distincte ou imprecise dans la famille. Les caracteristiques cliniques et EEG sont constantes: a lâge moyen de 6 mois, des convulsions breves, partielles (souvent secondairement generalisees), surviennent en ≪orages≫ de deux a 12 episodes par jour, sur une duree moyenne de 2,5 jours. LEEG critique montre une decharge focalisee; lEEG entre les crises est souvent lent et/ou avec des pointes focales, alors que lEEG a distance de lorage de crises est toujours normal. Il nexiste pas de difference nette entre les cas familiaux et non familiaux. Conclusion Ces caracteristiques cliniques et EEG permettent de reconnaitre un syndrome benin depilepsie du nourrisson, qui est de bon pronostic et dont le traitement doit rester peu agressif.

Study of clinical characteristics in young subjects with Developmental coordination disorder.

BACKGROUNDnDevelopmental Coordination Disorder (DCD) is a chronic neurological disorder observed in children. DCD is characterized by slowness in activities and motor impairment that affects the childrens daily living and academic achievements, and later their professional and social behavior. Our aim in this work was to report characteristics frequencies in a group of children with DCD and to propose a subtyping of DCD characteristics.nnnMETHODSnThirty three clinical DCD characteristics, the mostly reported in the literature, were assessed in 129 patients, boys and girls aged from 4years to 18years, and their subtyping was proposed. The statistical analyses were carried out with the Chi square, the t-test and the correlation for the statistical differences, and with the Ward clustering method for subtyping.nnnRESULTSnWe found that there were 3.17 boys for one girl, all patients were characterized as slow, 47% were left-handers or ambidextrous, 36% and 26% had orofacial and verbal dyspraxia, respectively, 83% were found anxious, and 84% were described as being clumsy.nnnCONCLUSIONSnIt appears from these results that a child with DCD expresses more than a single difficulty. Three subtypes emerged from the statistical analysis in this study: (1) clumsiness and other characteristics except language difficulties; (2) self-esteem and peer relation without clumsiness and language difficulties; (3) language difficulties and orofacial dyspraxia.

Insights in Developmental Coordination Disorder

BACKGROUNDnDevelopmental Coordination Disorder (DCD) is a neurological impairment occurring in nearly 6% of general population, and sometimes mimics other developmental disorders like Attention Deficit Hyperactivity Disorder (ADHD) or, in the most severe cases, intellectual deficiency.nnnOBJECTIVESnTo review the general portrait of DCD, the physiology, the clinical assessments, and to provide an overview of functional studies on the subject. We finally report some proposed DCD managements which vary depending on the manifestation of the disorder and on the goals of the therapy.nnnRESULTSnDCD can be stated as a sum of fine motor, perceptual visual and executive difficulties, emerging during childhood brain development and lasting throughout adulthood. Even if DCD can be isolated from other co-morbidities in certain individuals, it is still difficult to categorize it in delimited subclasses of characteristics, e.g. problems of vision or language. The findings in functional imaging also diverge in locating the cerebral deficit for a given motor task.nnnCONCLUSIONnFinding a single explanation seems difficult as many cerebral regions are associated with DCD and many clinical aspects are involved, but, further studies could explore genetic (or epigenetic) explanation for the prevalence of DCD in population.