RESUMEN
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
Asunto(s)
Parálisis Cerebral , Variaciones en el Número de Copia de ADN , Humanos , Niño , Variaciones en el Número de Copia de ADN/genética , Parálisis Cerebral/genética , Mutación , Secuenciación Completa del Genoma , GenómicaRESUMEN
Cerebral palsy (CP) is the most common movement disorder of childhood. Parents recognized the symptoms of CP at mean age of 13 months. However there was a mean delay of going to a doctor by 23 months and the mean age of diagnosis was 5½ years. Less than half of the CP children were diagnosed by a pediatrician and were receiving treatment methods with weak evidence base of efficacy. Delay in recognition of symptoms and help seeking due to lack of awareness and access to proper medical care and prevalent false beliefs were the leading reason for late diagnosis of CP in Nepal and thus children loose valuable time for intervention in their early developmental stage.
Asunto(s)
Parálisis Cerebral/diagnóstico , Parálisis Cerebral/epidemiología , Diagnóstico Tardío , Tiempo de Tratamiento , Adulto , Parálisis Cerebral/psicología , Niño , Preescolar , Estudios Transversales , Diagnóstico Tardío/psicología , Diagnóstico Tardío/tendencias , Femenino , Humanos , Masculino , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/epidemiología , Nepal/epidemiología , Padres/psicología , Médicos/psicología , Prevalencia , Estudios Prospectivos , Tiempo de Tratamiento/tendenciasRESUMEN
There is very little data pertaining to cerebral palsy (CP) from Nepal. In this retrospective study it was observed that dyskinetic CP was seen in 29 % and the sex ratio of males to females was two in the study population of children with CP. Both of these are much higher than data from developed countries. Hence, further randomized cross-sectional community based study is recommended to enquire into this pattern. Data regarding early identification was encouraging as majority of the cases (56 %) were diagnosed before 4 years of age. There is a stark necessity of early screening and rehabilitation program with provision for follow-up for the affected children, which must also be accessible to the disadvantaged and marginalized groups in Nepal.
