ABSTRACT
Pontocerebellar hypoplasia (PCH) type 12 is a rare, perinatal lethal neurodegenerative genetic disorder caused by biallelic mutations in the COASY gene. Herein, we describe the clinical and neuroradiological profile of nine affected fetuses/neonates from five families identified with a common COASY: c.1486-3C>G biallelic variant. Four of the five families were identified after data reanalysis of unresolved, severe PCH like phenotype and the fifth family through collaboration. The common antenatal phenotype was cerebellar hypoplasia. Microcephaly, arthrogryposis, and intrauterine growth restriction were the shared postnatal findings. The neurological manifestations included seizures, poor sucking, and spasticity. Novel findings of corpus callosum agenesis, simplified gyral pattern, normal sized pons, optic neuropathy, and a small thorax are reported in this series. The allele frequency of the COASY: c.1486-3C>G variant was 0.62% in the available Asian Indian database. We describe this as a possible common Indian origin variant. To the best of our knowledge, this is the largest PCH12 series reported.
Subject(s)
Cerebellar Diseases , Microcephaly , Transferases , Cerebellar Diseases/genetics , Female , Humans , Microcephaly/genetics , Mutation , Phenotype , Pregnancy , Transferases/geneticsSubject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Vitamin B 12 Deficiency/chemically induced , Aged , Diabetes Mellitus, Type 2/complications , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Metformin/therapeutic use , Middle Aged , Retrospective Studies , Treatment Outcome , Vitamin B 12/therapeutic use , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/drug therapy , Vitamin B Complex/therapeutic useABSTRACT
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