RESUMEN
BACKGROUND: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. METHODS: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. RESULTS: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. CONCLUSION: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.
Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/genética , Corteza Cerebral/anomalías , Predisposición Genética a la Enfermedad/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación/genética , Malformaciones del Sistema Nervioso/genética , Adolescente , Adulto , Movimiento Celular/genética , Cerebelo/anomalías , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Niño , Preescolar , Coristoma/genética , Coristoma/metabolismo , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Lactante , Masculino , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/fisiopatología , Penetrancia , FenotipoRESUMEN
BACKGROUND: Growth retardation is common in children with cerebral palsy. This may in part be due to the cerebral injury, but insufficient nutrition may also play a role. The aim of the present study was to estimate the prevalence of feeding problems, growth retardation, underweight and overweight in children with cerebral palsy. MATERIAL AND METHODS: Population-based study of children with cerebral palsy in two Norwegian counties. Information was obtained both from parents and from medical records. 154 children born between 1 January 1982 and 31 December 1996 were included in the study. RESULTS: 30% of the children had height below the 2.5th centile, 10% had weight for height below the 2.5th centile, and 7% were obese (weight above the 97.5th centile). 26% of the children had oral motor dysfunction and 33% were unable to self-feed. Although these problems were more prominent in children with severe forms of cerebral palsy, the results of the multivariate analyses suggested that lack of ability to self-feed was a significant independent risk factor for height growth retardation and underweight. Parents of 24 (15%) children reported that the family's quality of life was significantly impaired by the feeding problems of the child. INTERPRETATION: Our results are consistent with previous hospital-based studies and suggest that assessment of nutrition and growth should receive particular attention in the rehabilitation of children with cerebral palsy, in particular if the child is unable to self-feed.
