RESUMO
Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.
Assuntos
Anormalidades Múltiplas/genética , Hipotireoidismo Congênito/genética , Anormalidades Craniofaciais/genética , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Fatores de Transcrição NFI/genética , Síndrome de Sotos/genética , Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Hipotireoidismo Congênito/fisiopatologia , Anormalidades Craniofaciais/fisiopatologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Éxons/genética , Feminino , Deformidades Congênitas da Mão/fisiopatologia , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Megalencefalia/genética , Megalencefalia/fisiopatologia , Mutação de Sentido Incorreto/genética , Fenótipo , Displasia Septo-Óptica/genética , Displasia Septo-Óptica/fisiopatologia , Síndrome de Sotos/fisiopatologia , Adulto JovemRESUMO
Macrocephaly-capillary malformation (M-CM) is a genetic syndrome of unknown etiology characterized by an enlarged head circumference and patchy, reticular capillary malformation. We describe the clinical features of 13 cases, report on the genome-wide Copy Number Variation characterization of these patients, analyze the main clinical features of this syndrome and propose a modification of the current diagnostic criteria: the inclusion of both overgrowth/asymmetry and neuroimaging alterations as major criteria.
Assuntos
Anormalidades Múltiplas/diagnóstico , Capilares/anormalidades , Megalencefalia/diagnóstico , Mancha Vinho do Porto/diagnóstico , Telangiectasia/diagnóstico , Adolescente , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Frequência do Gene , Marcadores Genéticos , Genótipo , Humanos , Livedo Reticular , Masculino , Megalencefalia/patologia , Mancha Vinho do Porto/patologia , Dermatopatias Vasculares/genética , Síndrome , Telangiectasia/congênito , Telangiectasia/genética , Telangiectasia/patologiaRESUMO
The Simpson-Golabi-Behmel syndrome (SGBS) (OMIM 312870) is an overgrowth/multiple congenital anomalies syndrome caused by a semi-dominant X-linked gene encoding glypican 3 (GPC3). It shows great clinical variability, ranging from mild forms in carrier females to lethal forms with failure to thrive in males. The most consistent findings in SGBS are pre- and postnatal macrosomia, characteristic facial anomalies and abnormalities affecting the internal organs, skeleton, and on some occasions, mental retardation of variable degree. SGBS is also associated with an increased risk of developing embryonal tumors, mostly Wilms and liver tumors. We describe two molecularly-confirmed families with SGBS. All patients had typical manifestations of SGBS including some female relatives who had minor manifestations of the disorder. Some patients had novel findings such as a deep V-shaped sella turcica and six lumbar vertebrae. Molecular studies in affected patients showed a deletion of exon 6 in family 1 and an intronic mutation in family 2.