Syndrome de Silver Russell: à propos de 3 cas et revue de la litterature

Abstract Le syndrome de Silver Russell (SSR) est une maladie génétique rare. Sa prévalence est estimée à 1/100.000. Il s’agit d’une pathologie de l’empreinte parentale, caractérisée par une grande diversité phénotypique. Ses signes cliniques majeurs sont: un retard de croissance intra-utérin sévère, un retard staturo-pondéral post natal, une dysmorphie cranio-faciale particulière et une asymétrie des membres. Nous rapportons dans ce travail les observations de trois patients, qui présentent un retard staturo-pondéral, une dysmorphie faciale caractéristique du SSR et une hemihypertrophie corporelle. Nous discutons à travers ces cas les aspects cliniques et génétiques de ce rare syndrome.Pan African Medical Journal 2013; 14: 9

Clinical description and mutational profile of a moroccan series of patients with rubinstein taybi syndrome

Background: Rubinstein-Taybi syndrome (RSTS; OMIM 180849) is a rare autosomal dominant developmental disorder with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical face, broad thumbs and halluces, short stature, and intellectual disability. Facial dysmorphy is characteristic with microcephaly, low frontal hairline, arched eyebrows, long eyelashes, convex profile of nose, narrow palate, and micrognathia. RSTS is mainly due to mutations or microdeletions of the CREBBP gene (about 60%) and more rarely of the EP300 gene (8%). Objective: Clinical description and identification of mutations of patients with Rubinstein Taybi syndrome Methods: PCR and direct sequencing of CREBBP gene. Results: We report here, the clinical and molecular data of a series of six Moroccan patients with a phenotype of RSTS. The molecular study of the major gene CREBBP (by Sanger Sequencing followed by CGH array, if sequence normal) revealed point mutations in five patients. For the sixth patient, CGH array revealed a microdeletion carrying the CREBBP gene. Through this work, we emphasize the importance of clinical expertise in the diagnosis, management and genetic counseling in Rubinstein Taybi syndrome

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Heimler Syndrome is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities and occasional or late onset retinal pigmentation. We ascertained eight families with HS, and - using a whole exome sequencing approach - identified biallelic mutations in PEX1 or PEX6 in six of them. Loss of function mutations in both genes are known causes of a spectrum of autosomal recessive peroxisome biogenesis disorders (PBDs), including Zellweger syndrome. PBDs are characterized by leukodystrophy, hypotonia, SNHL, retinopathy, and skeletal, craniofacial, and liver abnormalities. We demonstrate that each HS family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. Although individuals with HS share some subtle clinical features found in PBDs, the overlap is minimal and the diagnosis was not suggested by routine blood and skin fibroblast analyses used to detect PBDs. In conclusion, our findings define Heimler syndrome as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6

A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder. It is a spondyloepimetaphyseal dysplasia associated with mental retardation. Clinical manifestations include coarse facies, microcephaly, short trunk dwarfism, and mental retardation. Mutations in Dymeclin gene (DYM), mapped to chromosome 18q21.1, is responsible for DMC. We report here the observation of a consanguineous Moroccan patient having DMC syndrome. The molecular studies showed a previously reported homozygous mutation at c.1878delA of DYM gene. We discuss this recurrent mutation in Moroccan patients with DMC syndrome with a review

A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder. It is a spondyloepimetaphyseal dysplasia associated with mental retardation. Clinical manifestations include coarse facies, microcephaly, short trunk dwarfism, and mental retardation. Mutations in Dymeclin gene (DYM), mapped to chromosome 18q21.1, is responsible for DMC. We report here the observation of a consanguineous Moroccan patient having DMC syndrome. The molecular studies showed a previously reported homozygous mutation at c.1878delA of DYM gene. We discuss this recurrent mutation in Moroccan patients with DMC syndrome with a review

Clinical and molecular findings in a Moroccan patient with popliteal pterygium syndrome: a case report

International audienceIntroduction: Popliteal pterygium syndrome is a congenital malformation that includes orofacial, musculoskeletal and genitourinary anomalies. It is a rare autosomal dominant disorder due to a mutation of the IRF6 gene on 1q32.2.Case presentation: A one-month-old Moroccan baby boy was diagnosed with typical features of popliteal pterygium syndrome and carried the c.250C>T; p.Arg84Cys mutation of the IRF6 gene.Conclusions: We report on the first description of a Moroccan popliteal pterygium syndrome patient. This diagnosis allowed us to provide an appropriate course of management to the patient and offer genetic counseling to his family