RESUMO
Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.
Assuntos
Transtornos Dismórficos Corporais/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Metiltransferases/genética , Adolescente , Adulto , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 3/genética , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Penetrância , Fenótipo , Sequenciamento do Exoma , Adulto JovemRESUMO
We report on three patients with terminal deletions of chromosome 10q and compare them to 15 previously reported patients. A similar facial appearance with a prominent beaked nose, large and/or malformed ears, and a pattern of major abnormalities including severe mental retardation, cardiac anomalies, and anogenital anomalies are reviewed. We feel the manifestations of del 10qter are sufficiently distinct to suggest this diagnosis on clinical examination.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 10 , Anormalidades Múltiplas/patologia , Aberrações Cromossômicas/patologia , Bandeamento Cromossômico , Face/anormalidades , Feminino , Humanos , Recém-Nascido , Masculino , FenótipoRESUMO
Planning of service delivery systems for children with special health care needs would be enhanced by knowledge of numbers of cases anticipated in defined geographic areas. A method is described for predicting numbers of children who will likely have mental retardation sufficient to require special education services, based on the birth prevalence of birth defects and clinicians' estimates of the likelihood of mental retardation associated with each specific birth defect. This method is applied to the 1980-82 birth cohort of a 28-county area of south and central Arkansas, and it is compared with special education enrollment data for children ages 6 to 8 in academic year 1988-89. According to this estimate, children with birth defects may account for 32 to 56 percent of the cases of mental retardation among 6- to 8-year-olds reported by the public schools.