Gillespie syndrome in a South Asian child: a case report with confirmation of a heterozygous mutation of the ITPR1 gene and review of the clinical and molecular features

BMC Pediatr. 2018 Sep 24;18(1):308. doi: 10.1186/s12887-018-1286-5.

Abstract

Background: Gillespie syndrome is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia, non-progressive cerebellar ataxia and intellectual disability. Homozygous and heterozygous pathogenic variants of the ITPR1 gene encoding an inositol 1, 4, 5- triphosphate- responsive calcium channel have been identified in 13 patients recently. There have been 22 cases reported in the literature by 2016, mostly from the western hemisphere with none reported from Sri Lanka.

Case presentation: A 10-year-old girl born to healthy non-consanguineous parents with delayed development is described. She started walking unaided by 9 years with a significantly unsteady gait and her speech was similarly delayed. Physical examination revealed multiple cerebellar signs. Slit lamp examination of eyes revealed bilateral partial aniridia. Magnetic resonance imaging of brain at the age of 10 years revealed cerebellar (mainly vermian) hypoplasia. Genetic testing confirmed the clinical suspicion and demonstrated a heterozygous pathogenic variant c.7786_7788delAAG p.(Lys2596del) in the ITPR1 gene.

Conclusion: The report of this child with molecular confirmation of Gillespie syndrome highlights the need for careful evaluation of ophthalmological and neurological features in patients that enables correct clinical diagnosis. The availability of genetic testing enables more accurate counseling of the parents and patients regarding recurrence risks to other family members.

Keywords: Cerebellar hypoplasia; Gillespie syndrome; ITPR1 gene; Partial aniridia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniridia / diagnosis
  • Aniridia / diagnostic imaging
  • Aniridia / genetics*
  • Brain / diagnostic imaging
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / diagnostic imaging
  • Cerebellar Ataxia / genetics*
  • Child
  • Female
  • Heterozygote*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / genetics*
  • Intellectual Disability / diagnosis
  • Intellectual Disability / diagnostic imaging
  • Intellectual Disability / genetics*
  • Magnetic Resonance Imaging
  • Mutation*
  • Sri Lanka

Substances

  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors

Supplementary concepts

  • Aniridia cerebellar ataxia mental deficiency