Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not show a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases.

Prevalence and characteristics of children with mild intellectual disability in a French county.

BACKGROUND: Studies conducted on mild intellectual disability (MID) in children are infrequent and the prevalence rates vary widely. This study aimed to estimate the prevalence of MID in children in a French county (Isère), to describe the clinical signs and associated comorbidities, and to specify the aetiologies of this disability. METHODS: The target population was comprised of the 15 100 children born in 1997 residing in Isère County, France, in 2008. Our goal was to find the children in this group with MID diagnosed between 9 and 13 years of age. MID was defined as an overall IQ score of between 50 and 69 [International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)]; this definition was adjusted for the study by integrating confidence intervals so that the risk of IQ measurement relativity and possible discrepancy of scores could be taken into account. Children were identified through an administrative data source designed to assist disabled persons that contains health information, and an educational data source. Parents who agreed to let their children participate responded to an in-depth questionnaire on their child's medical and academic history. A genetic investigation was proposed for those children whose MID had an unknown aetiology. RESULTS: The preliminary selection included 267 children, resulting in a prevalence rate of 18 per 1000 (CI [15.6; 19.9]), within the expected mean. Of these 267 cases, 181 families agreed to participate in the study (68%). MID more often affected boys [male gender ratio = 1.4 (CI [1.2; 1.6])], low socioeconomic groups, and families with a history of intellectual disability. The clinical signs and comorbidities associated with MID were very frequent, with 54% spoken language disorders and 10% pervasive developmental disorder. Only 9% of the children had undergone a genetic investigation before the study. The known aetiology rate for MID was 19% among all the children who had had genetic tests performed. CONCLUSION: MID is an important public health issue based on its prevalence. The associated clinical signs and comorbidities may be warning signs of MID in case of learning difficulties. This study may help decision-makers to develop and organise screening and care for MID.

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis.

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than - 2. The mean lumbar spine Z score (- 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than - 2, respectively. The mean femoral neck (- 1.1 ± 1.1) and total hip (- 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = - 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

Brachytelephalangic chondrodysplasia punctata: prenatal diagnosis and postnatal outcome.

We report the prenatal management of a brachytelephalangic chondrodysplasia punctata (CDPX1) case and how postnatal findings confirmed the diagnosis. The mother was initially referred after ultrasound revealed an abnormal fetal mid-face and punctuation of upper femoral epiphyses. Chondrodysplasia punctata (CP) with Binder anomaly was suspected. 3D-HCT revealed brachytelephalangy suggesting CDPX1. At birth, mid-face hypoplasia was marked. Postnatal imaging and genetic analysis confirmed the initial diagnosis. Binder anomaly is probably always associated with CP. The newly revised CP classification facilitates the diagnosis. The main etiologies are metabolic and chromosomal abnormalities, and arylsulfatase E enzyme dysfunction. Thus, screening for arylsulfatase E mutation is mandatory for an accurate diagnosis and can lead to better delineation among CP etiologies associated with a Binder phenotype.

[Function of aurora kinase C (AURKC) in human reproduction]. / Rôle d'aurora kinase C (AURKC) dans la reproduction humaine.

Infertility concerns at least 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. Hundreds of genes are probably involved in spermatogenesis and oogenesis and this genetic heterogeneity has so far hindered the identification of genes causing infertility in the human. Careful morphological examination of spermatozoa can provide cues to identify homogeneous cohorts of patients likely to have the same genetic defect. We studied a cohort of North-Africans patients with a rare phenotype of large-headed spermatozoa. Using a homozygosity mapping strategy, we could map the morbid gene and we identified the same homozygous mutation (c.144delC) in the aurora kinase C gene (AURKC) of all patients studied initially. We then genotyped a total of 62 patients. All who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n=34), whereas no AURKC mutations were detected in the others. A carrier frequency of 1/50 was established from individuals from the Maghrebian population, indicating that 1 in 10,000 men from North-African can be expected to present this form of infertility, a frequency comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. Then we demonstrated by flow cytometry that all spermatozoa have in fact a homogeneous 4C. We recommend the realisation of a molecular diagnosis to all patients with large-headed spermatozoa. ICSI is formally contraindicated for all homozygous patients who can have recourse to donor sperm or adoption. One cannot be as categorical for the patients not harbouring an AURKC mutation.

[Type 1 neurofibromatosis: Onset of two tumors before the age of 5years]. / Neurofibromatose de type 1 : survenue de deux tumeurs avant l'âge de 5 ans.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant genetic disorder that predisposes to the development of benign and malignant tumors. Mutation of the NF1 gene affects the RAS-MAPK signaling pathway and leads to a dysfunction in cell proliferation and induces tumor development. Epidemiology of cancer in children with NF1 is very different from the general pediatric population, which requires regular and specific monitoring. Neurofibroma is the most frequent benign tumor. It can be very invalidating depending on the size and location of the tumor. Currently, there is no specific treatment for these tumors. The most frequent malignancies in children with NF1 are leukemias, rhabdomyosarcomas, malignant peripheral nerve sheath tumors and gliomas. The treatment of these tumors should consider the risk of second cancers induced by radio- and chemotherapy. We report on the case of a 5-year-old boy with NF1 developing two tumors.

[Schooling and care of mild intellectual disability children]. / Parcours scolaire et prise en charge médico-éducative des enfants avec déficience intellectuelle légère.

Studies on mild intellectual disability (MID) are scarce. The aim of this study was to describe the educational and medical care trajectories and their determinants in children with MID. The study population concerned children born in 1997 and resident in a French county (Isère) in 2008. MID was defined as an overall IQ score between 50 and 69. For the present study, this definition was adjusted by integrating the IQ confidence intervals so that the risk of IQ measurement relativity and possible score discrepancy could be taken into account. Of the 267 children included, 180 (67%) were identified through an institute that decides upon special education and allowances (MDPH) and 87 (33%) through the educational system. The parents of 181 children (68%) accepted to answer a telephone questionnaire, describing their child's educational and medical history. Children with MID frequently presented clinical signs and comorbidities. Educational trajectories were quite varied: a majority of the children (52.9%) were oriented toward sections with adapted general and professional education (SEGPA) after finishing primary school, a minority (41.3%) were oriented towards specialized schools, such as medical-educational institutions, and a small proportion of children (5.8%) stayed in ordinary school. Children followed the SEGPA orientation more frequently when a relative written language disorder was present, and autism-spectrum disorders or other clinical signs were absent. Concerning follow-up care and rehabilitation, children mostly took part in speech therapy (76.2%) and psychotherapy (55.8%). The French law dating from 2005, ensuring equal opportunity for people with disabilities, has borne fruit in the diversification of educational trajectories.

Corticotropin-releasing factor receptors in human small cell lung carcinoma cells: radioligand binding, second messenger, and northern blot analysis data.

Numerous peptides, growth factors, and receptors have been identified in small cell lung carcinoma (SCLC) cells. The present study was designed to examine the radioligand binding, second messenger, and messenger RNA (mRNA) characteristics of CRF receptors in a variety of SCLC lines and to compare their characteristics to CRF receptors in the mouse pituitary tumor AtT-20 cells. The human SCLC cell lines NCI-H69, H82, H146, H209, H345, H446, and H510A and control AtT-20 cells all demonstrated specific [125I]Tyr(o)-ovine CRF ([125I]oCRF) binding, which was linear with increasing protein concentrations, saturable, reversible, and of high affinity. NCI-H82 cells showed the highest level of specific [125I]oCRF binding (approximately 60% of the total binding). Scatchard analysis revealed a single homogeneous class of binding sites in NCI-H82 and AtT-20 cells, with Kd values of 263 +/- 48 and 285 +/- 75 pM, respectively, and binding capacities of 74 +/- 7 and 70 +/- 13 fmol/mg protein, respectively. [125I]oCRF-binding sites on NCI-H82 and AtT-20 cells had comparable pharmacological characteristics with the following rank order of inhibitory potencies: rat/human CRF approximately ovine CRF approximately bovine CRF > alpha-helical oCRF-(9-41) > bovine CRF-(1-41)OH >> vasoactive intestinal peptide, secretin, GH-releasing hormone. [125I]oCRF binding in the cell lines was inhibited by guanine nucleotides, suggesting a coupling of receptors to guanine nucleotide-binding proteins. The functional nature of the CRF receptor was demonstrated in second messenger studies in which rat/human CRF stimulated cAMP production in NCI-H82 and AtT-20 cells with comparable EC50 values of about 3 nM; the percent stimulation over basal activity was significantly higher in NCI-H82 cells (approximately 30-fold increase) than in AtT-20 cells (approximately 12-fold increase). Northern blot analysis of total RNA revealed the presence of a 2.6-kilobase mRNA band in NCI-H82 cells corresponding to the recently cloned human CRF receptor. In summary, the data demonstrate the presence of CRF receptors in SCLC cell lines with kinetic, pharmacological, second messenger, and mRNA characteristics comparable to those in pituitary and brain and suggest a possible role for CRF as a regulatory peptide in human SCLC.

Mutation and expression analysis of corticotropin-releasing factor 1 receptor in adrenocorticotropin-secreting pituitary adenomas.

The present study was designed to investigate a possible role of CRF1 receptors (CRF1-R) in the pathogenesis of Cushing's disease. ACTH-secreting pituitary adenomas and nonsecreting pituitary adenomas have been analyzed for mutations in the CRF1-R gene by PCR and sequencing and been compared with the sequences of normal anterior pituitaries. No mutations affecting the CRF1-R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF1-R messenger RNA in ACTH-secreting pituitary adenomas vs. inactive adenomas and normal pituitaries. We conclude that mutations of the CRF1-R are unlikely to be involved in Cushing's disease. We suggest that the overexpression of the CRF1-R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas.

Expression of members of the interleukin-6 family of cytokines and their receptors in human pituitary and pituitary adenomas.

There is increasing evidence for the role of members of the Interleukin (IL)-6 family in pituitary function, particularly in the regulation of the hypothalamo-pituitary-adrenal axis. However, there is only a limited amount of data available on the expression in human normal and tumorous pituitary tissue. In this study we investigated the expression of members of the IL-6 family of cytokines and their receptors in normal human pituitaries as well as pituitary adenomas using the RT-PCR technique. Eighteen pituitary adenoma biopsies removed in transsphenoidal surgery (six corticotrophic adenomas, four nonfunctioning adenomas, four somatotrophinomas, four prolactinomas) and six normal anterior pituitaries were examined for the expression of IL-6 receptor (-R), leukemia inhibitory factor (LIF), LIF-R, IL-11, IL-11-R, oncostatin M (OSM), OSM-R, ciliary neurotrophic factor (CNTF), CNTF-R and cardiotrophin-1 (CT-1). All pituitaries and pituitary adenomas expressed OSM transcripts, whereas no expression of CT-1 was found. The expression of all other cytokines (LIF, IL-11, CNTF) and receptors (IL-6-R, LIF-R, IL-11-R, OSM-R, CNTF-R) was found in different patterns in the adenoma subtypes and normal pituitaries. However, we did not detect expression of LIF-, IL-11-, IL-6-R and CNTF-R in prolactinomas, of CNTF in normal pituitaries and of OSM-R in ACTH-secreting adenomas. In conclusion, our study provides further evidence for a role of the members of the IL-6 family of cytokines in pituitary function.

Functional corticotropin-releasing factor receptors in human neuroblastoma cells.

The present study examined the presence of functional corticotropin-releasing factor (CRF) receptors in IMR-32 neuroblastoma cells. [125I]Tyro-ovine CRF binding was linear with increasing protein concentrations, saturable, reversible and of high affinity. Scatchard analysis indicated a Kd of approximately 0.8 nM and a Bmax of approximately 32 fmol/mg protein. Competition studies with CRF and related peptides revealed a pharmacological profile characteristic of the CRF1 receptor subtype. CRF stimulated cAMP production in a dose-dependent manner with an apparent EC50 of approximately 4 nM. In addition, the putative CRF receptor antagonist alpha-helical CRF9-41 dose-dependently inhibited CRF stimulated (10 nM) cAMP production with an IC50 of approximately 60 nM. CRF treatment down regulated its own receptor while treatment with the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), increased CRF binding in neuroblastoma cells. Taken together, these data demonstrate the utility of the human neuroblastoma cell line for functional studies on CRF receptors and suggest that CRF may play a regulatory role in the pathophysiology of human neuroblastoma.

Homologous desensitization of human corticotropin-releasing factor1 receptor in stable transfected mouse fibroblast cells.

Previous radioligand binding and second messenger studies have shown that corticotropin-releasing factor (CRF) modulates its receptor following both in vivo and in vitro treatment. In the present study, we determined the sequence of events leading to CRF-induced downregulation and desensitization of cloned CRF receptors in murine fibroblast cells (Ltk-) stably transfected with CRF1 DNA (from human pituitary). Treatment of cells with rat/human CRF produced a dose- and time-dependent decrease in [125I]Tyr degrees-ovine CRF ([125I]oCRF) binding and a concomitant decrease in CRF-stimulated adenylate cyclase activity. Significant decreases in [125I]oCRF binding and agonist-stimulated cAMP production were evident minutes after CRF treatment with maximal (60-80%) reductions seen following 1 h of CRF treatment. Scatchard analysis revealed that the decrease in [125I]oCRF binding was due to the downregulation of the receptor with no significant alteration seen in the affinity of the ligand. Since the transfected cell line is engineered using an artificial promoter, we did not detect any significant changes in CRF1 receptor mRNA levels following CRF treatment for up to 24 h.

Cyclic AMP-dependent modulation of interleukin-1 receptors in the mouse AtT-20 pituitary tumor cell line.

Previous studies have demonstrated an upregulation of interleukin-1 (IL-1) receptors following treatment of mouse AtT-20 pituitary tumor cells with corticotropin-releasing factor (CRF). In the present study, we determined the modulation of IL-1 receptors and adenylate cyclase activity in AtT-20 cultures following treatment with CRF, isoproterenol, forskolin, somatostatin and dexamethasone. CRF, isoproterenol and forskolin dose-dependently increased cAMP production and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding. Parallel modulation of IL-1 receptors by agents that stimulate (CRF, isoproterenol and forskolin) or inhibit (somatostatin) cAMP production in AtT-20 cells suggest the importance of this second messenger in regulating IL-1 receptors.

[Representative enzymes of energy supplying metabolism in the normal and denervated human brachial biceps, deltoid and anterior tibial muscles (author's transl)]. / Repräsentative Enzyme des energieliefernden Stoffwechsels im normalen und denervierten M. biceps brachii, M. deltoideus und M. tibialis anterior des Menschen

Representative enzyme activities of energy supplying metabolism were measured in muscle specimens of brachial biceps, deltoid or anterior tibial muscle of patients with affections of the peripheral nerves. Simultaneously performed measurements of the same enzyme activities in the contralateral normal muscles served as a control. 5 patients suffered from a lesion of the brachial plexus, 7 patients had a paralysis of the axillary nerve, and 8 patients had a peroneal paralysis. In all denervated muscles no electrophysiological signs of reinnervation were present. The activities of glycogen phosphorylase, triosephosphate dehydrogenase, lactate dehydrogenase and alpha-glycerophosphate dehydrogenase were found to be highest in the normal brachial biceps muscle. Lower activities were measured in the normal deltoid and anterior tibial muscle. The oxidative enzymes, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase as well as hexokinase, showed no significant difference from the levels of the control. It is suggested that a probable factor determining the differences of the enzyme activities of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation between brachial biceps, deltoid and anterior tibial muscle, might be the pattern of impulse activity in the motor nerves of these muscles. The enzyme activities of glycogen phosphorylase, triosephosphate dehydrogenase, lactate dehydrogenase and alpha-glycerophosphate dehydrogenase, decreased rapidly during the first 2 months after denervation in the brachial biceps, deltoid and anterior tibial muscle, whereas the decrease was slight during the following months. The activities of the oxidative enzymes (3-hydroxyacyl-CoA dehydrogenase and citrate synthase) showed no significant change after denervation. The metabolic difference of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation between the three muscles was no longer maintained. The possible causes of the deeply decreased enzyme activities of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation, as well as the causes of the unchanged oxidative enzyme activities and of the increased hexokinase activity after denervation in the human brachial biceps, deltoid and anterior tibial muscle, are discussed.

Decreased expression of corticotropin-releasing factor-binding protein mRNA in ACTH-secreting pituitary adenomas.

This study was designed to analyze the sequence and the expression of CRF-BP mRNA in ACTH-secreting pituitary adenomas. Direct sequencing analysis revealed no apparent mutations in the CRF-BP mRNA. Thus, we conclude that mutations in the coding region of the CRF-BP gene are not involved in the pathogenesis of Cushing's disease. However, using a semiquantitative PCR approach coamplifying the house-keeping gene GAPDH we detected a reduced expression of CRF-BP mRNA in ACTH-secreting pituitary adenomas when compared with normal pituitaries. We suggest that the decreased CRF-BP gene expression in ACTH-secreting pituitary adenomas is most likely an effect due to high cortisol levels in Cushing patients.

Expression of leptin receptor mRNA and the long form splice variant in human anterior pituitary and pituitary adenoma.

Expression of leptin receptor (OB-R) mRNA was detected in the human anterior pituitary as well as in ACTH-secreting and nonsecreting pituitary adenomas by RT-PCR with primers recognizing all receptor splice variants. Primers specific to the long splice variant of the leptin receptor (OB-Rb), containing the putative intracellular signalling domain, also revealed a strong expression in normal and adenomatous anterior pituitaries. These results indicate that the pituitary is a possible target tissue of leptin action and might be involved in leptin regulation of pituitary hormone secretion.

Corticotropin-releasing factor receptors: an overview.

Corticotropin-releasing factor (CRF) is the primary physiological regulator of basal and stress-induced release of ACTH, beta-endorphin and other POMC-derived peptides from the pituitary and plays a major role in the brain and periphery in coordinating endocrine, electrophysiological, autonomic, behavioral and immune responses to stress. In addition, recent clinical data implicate CRF in the etiology and pathophysiology in a variety of endocrine, psychiatric and neurodegenerative disorders. The various effects of CRF are mediated by two distinct CRF receptors expressed at high levels in selected brain areas, but also at different levels in several other non-neuronal tissues. This chapter provides an overview of the current knowledge about CRF receptors including tissue specificity and regulatory aspects as well as molecularbiological, biochemical and pharmacological characteristics. In addition, neuroimmune, neuroendocrine and behavioral-related implications of the CRF receptor as well as its involvement in a variety of disorders are discussed. This review summarizes four decades of research beginning with the search for the factor that governs the release of ACTH and getting to the recent findings including the successful cloning of different receptor subtypes and the discovery of a new endogenous CRF-related ligand.

Mutation analysis of leukemia inhibitory factor-receptor (LIF-R) in ACTH-secreting pituitary adenomas.

Numerous cytokines and particularly leukemia inhibitory factor (LIF) are involved in the differentiation, proliferation, and secretory function of ACTH-producing pituitary cells. LIF and its receptor LIF-R are abundantly expressed in normal pituitaries and in ACTH producing adenomas. The present study was performed to evaluate the possible role of LIF-R in the pathogenesis of ACTH-secreting pituitary adenomas. To test the hypothesis that a possible mutation of LIF-R might be involved in pathogenesis of Cushing's disease we analyzed ACTH-producing pituitary adenomas as well as inactive pituitary adenomas by RT-PCR and direct cycle sequencing. No mutations have been found in the adenomas investigated. We thus conclude that mutations in LIF-R are an unlikely cause for the development of Cushing's disease.

[Five hundred outpatient hernioplasties using the Lichtenstein method]. / Ambulante Hernioplastik nach Lichtenstein. 500 ambulante Herniotomien in einer chirurgischen Praxis.

UNLABELLED: The Lichtenstein repair method is an excellent and simple technique for hernia repair performed as a day-case procedure. A consecutive series of 500 ambulatory groin hernia repairs from 1994 to 2002 was studied. The mean follow-up for 84.6% of the patients was 2 years (range 6-86 months). There were no severe complications. The rate of clinically important wound haematomas (n=6, 1.2%) was low, as well as the numbers of testicular atrophies (n=1, 0.2%) and deep wound infection (n=1, 0.2%). We saw no thrombosis. There were 15 recurrences (3.5%). Ninety-six per cent of the patients were satisfied with the outpatient operation. In day-case surgery, conditions for the patients' treatment at home should be checked carefully by surgeons before the operation. CONCLUSION: Our results suggest that the number of day-case hernia repairs can be increased without severe complications. The procedure can be performed on an outpatient basis without problems under general anaesthesia. Increasing day-case surgery could significantly reduce the costs of health care.

[A rare cause of respiratory failure in infants: distal spinal-muscular atrophy 1 (DSMA1 or SMARD1)]. / Une cause rare d'insuffisance respiratoire aiguë chez le nourrisson : l'amyotrophie spinale distale de type 1 (DSMA1 ou SMARD1).

Distal spinal-muscular atrophy 1 (DSMA1) or spinal-muscular atrophy with respiratory distress type 1 (SMARD1) is a rare neuromuscular disorder resulting from IGHMBP2 mutations. It is an autosomal recessive disease. We present the case of a 1-year-old girl admitted for respiratory failure associated with pneumonia. Right hemidiaphragmic elevation on the chest radiograph and distal retractions suggested the diagnosis of DSMA1. It was confirmed by muscle biopsy and molecular analysis. This unrecognized diagnosis should be considered when respiratory failure develops in the first year of life and is associated with diaphragmatic paralysis and distal muscle atrophy. Electromyography with measurement of nerve conduction velocity and muscle biopsy suggest the diagnosis, which must be confirmed by genetic analysis. After identifying the mutations, it is possible to perform prenatal diagnosis.