Genotype-phenotype correlation of congenital anomalies in multiple congenital anomalies hypotonia seizures syndrome (MCAHS1)/PIGN-related epilepsy.

Journal Article (Journal Article)

Mutations in PIGN, resulting in multiple congenital anomalies-hypotonia-seizures syndrome, a glycosylphosphatidylinositol anchor deficiency, have been published in four families to date. We report four patients from three unrelated families with epilepsy and hypotonia in whom whole exome sequencing yielded compound heterozygous variants in PIGN. As with previous reports Patients 1 and 2 (full siblings) have severe global developmental delay, gastroesophageal reflux disease, and minor dysmorphic features, including high palate, bitemporal narrowing, depressed nasal bridge, and micrognathia; Patient 3 had early global developmental delay with later progressive spastic quadriparesis, intellectual disability, and intractable generalized epilepsy; Patient 4 had bilateral narrowing as well but differed by the presence of hypertelorism, markedly narrow palpebral fissures, and long philtrum, had small distal phalanges of fingers 2, 3, and 4, absent distal phalanx of finger 5 and similar toe anomalies, underdeveloped nails, unusual brain anomalies, and a more severe early clinical course. These patients expand the known clinical spectrum of the disease. The severity of the presentations in conjunction with the patients' mutations suggest a genotype-phenotype correlation in which congenital anomalies are only seen in patients with biallelic loss-of-function. In addition, PIGN mutations appear to be panethnic and may be an underappreciated cause of epilepsy.

Full Text

Duke Authors

Cited Authors

  • Fleming, L; Lemmon, M; Beck, N; Johnson, M; Mu, W; Murdock, D; Bodurtha, J; Hoover-Fong, J; Cohn, R; Bosemani, T; Barañano, K; Hamosh, A

Published Date

  • January 2016

Published In

Volume / Issue

  • 170A / 1

Start / End Page

  • 77 - 86

PubMed ID

  • 26394714

Pubmed Central ID

  • PMC4886552

Electronic International Standard Serial Number (EISSN)

  • 1552-4833

Digital Object Identifier (DOI)

  • 10.1002/ajmg.a.37369


  • eng

Conference Location

  • United States