ICNC Abstracts, ICNC 2018

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X linked infantile epileptic encephalopathy due to SMC1A truncating mutation - ‘An emerging phenotypic syndrome’
Ami Shah, Neeta Naik, Salil Gundewar

Last modified: 2018-09-09


Till date PCDH19 related early onset epilepsy, with fever sensitive seizure clusters and mild developmental impairment was the only well described X linked epileptic encephalopathy.  SMC1A truncating mutations have recently been described in fifteen females with early onset epileptic encephalopathy and absence of typical features of Cornelia de Lange Syndrome (CdLS).

We describe a 17-month girl born of non-consanguineous marriage who presented with moderate motor delay, severe impairment in speech and social communication and self-absorbed behavior. She had clusters of generalized negative myoclonic seizures on awakening and episodes of non-convulsive status epilepticus since 9 months of age. She regressed further after seizure onset. She had flattened mid face, short nose, small philtrum, microcephaly, short stature, hypertrichosis and hypotonia on examination. EEG showed frequent generalized spike and wave abnormalities with occasional background suppression. MRI was normal. Seizures were pharmacoresistant but showed marked and sustained reduction after ketogenic diet with marginal improvement in development.

Gene panel identified a heterozygous frameshift deletion (c.3305_3312del) in SMC1A gene (OMIM entry *300040) predicted to cause a premature termination of protein.  Missense mutations or small in frame deletions in this gene are associated with X-linked CdLS (OMIM entry # 300590). Some phenotypic similarity with CdLS was seen in our case in the form of short stature, microcephaly and developmental delay. But presence of seizure clusters, pharmacoresistant epilepsy, severity of developmental impairment and subtle facial dysmorphisms were features distinct from CdLS.

This emerging phenotype should be considered in females with early onset refractory epileptic and developmental encephalopathy.


Epileptic encephalopathy; X-linked; SMC1A; Cornelia de Lange

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