RESUMEN
Opitz-Kaveggia syndrome is a rare X-linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty-three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz-Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.
Asunto(s)
Complejo Mediador/genética , Mutación , Síndrome Acrocallosal/genética , Adolescente , Agenesia del Cuerpo Calloso , Secuencia de Aminoácidos , Ano Imperforado/genética , Estreñimiento/genética , Humanos , Lactante , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/genética , Datos de Secuencia Molecular , Hipotonía Muscular/congénito , Hipotonía Muscular/genética , Linaje , Alineación de SecuenciaRESUMEN
Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with various array platforms, we detected 22 individuals (14 index patients and 8 family members) with deletions in 16p11.2, which are genomically identical to those identified in the autism studies. Though some patients shared a facial resemblance and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism was not the presenting feature in our series. The assembled evidence indicates that recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges from MR and/or MCA, autism, learning and speech problems, to a normal phenotype.
Asunto(s)
Trastorno Autístico/genética , Deleción Cromosómica , Cromosomas Humanos Par 16 , Discapacidad Intelectual/genética , Anomalías Múltiples , Adolescente , Adulto , Niño , Preescolar , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Pruebas Genéticas , Humanos , Lactante , Discapacidades para el Aprendizaje , Masculino , Trastornos del Habla , Adulto JovenRESUMEN
A 22-month-old girl had cramps and stiffness of her muscles. After medical history, physical examination and an EMG, a short differential diagnosis based on the symptoms of myotonia was made. Initially, the symptoms were incorrectly assumed to be due to Becker's myotonia, an autosomal recessive condition caused by a mutation in the chloride channel. Molecular analysis did not show a defect in the chloride channel, but instead a defect in the sodium channel of the muscle fibre. Since defects in the sodium channel are responsible for several myotonic diseases, further analysis was necessary. Based on knowledge of the structure and mechanism of the sodium channel and study of literature on cases involving the identical mutation, the diagnosis 'potassium-aggravated myotonia' (PAM) was made. Re-evaluation of the patient showed that her symptoms fitted the diagnosis 'myotonia permanens', the severest form of PAM. She was treated with mexiletine. In myotonia several features can give direction to the diagnosis, including sensitivity to temperature and exercise, and family history. However, it is often necessary to use molecular analysis to be able to diagnose the disease correctly, make a prognosis and predict the risk of recurrence as well as to formulate a treatment plan.
Asunto(s)
Calambre Muscular/genética , Miotonía/diagnóstico , Miotonía/genética , Canales de Sodio/genética , Análisis Mutacional de ADN , Diagnóstico Diferencial , Electromiografía , Femenino , Humanos , Lactante , Músculo Esquelético/inervación , Potasio/efectos adversos , Canales de Sodio/metabolismoRESUMEN
MR spectroscopy results in a mild case of guanidinoacetate methyltransferase (GAMT) deficiency are presented. The approach differs from previous MRS studies in the acquisition of a chemical shift imaging spectral map showing gray and white matter with the corresponding spectra in one overview. MR spectroscopy revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA signals are more prominent in gray matter than in white. In the prevailing view, that enzyme deficiency is localized in liver and pancreas and that all GAA is transported into the brain from the blood and the cerebrospinal fluid, this would be compatible with a more limited uptake and/or better clearance of GAA from the white matter compared to the grey matter.