Clinical presentation and evolution of Xia-Gibbs syndrome due to p.Gly375ArgfsTer3 variant in a patient from DR Congo (Central Africa)

Am J Med Genet A. 2021 Mar;185(3):990-994. doi: 10.1002/ajmg.a.62049. Epub 2020 Dec 29.

Abstract

Xia-Gibbs syndrome (XGS) is a very rare genetic condition. The clinical spectrum is very broad and variable. The phenotype and evolution in a Congolese boy with XGS have been reported. At 6 years he had speech delay, drooling, marked hyperactivity, attention deficit, aggressive behavior, and intellectual disability. Dysmorphological evaluation revealed strabismus, mild unilateral ptosis, uplifted ear lobes, flat philtrum, thin upper lip vermillion, high arched palate, and flat feet. Patient-only whole exome sequencing identified a known pathogenic frameshift variant in the AHDC1 gene [NM_001029882.3(AHDC1):c.1122dupC;(p.Gly375ArgfsTer3)]. The clinical follow-up revealed the deterioration of his fine motor skills and significant cerebellar phenotype including tremor, pes cavus, and gait instability at the age of 12 years. This patient was compared with three previously reported patients with the same variant but did not identify a consistent pattern in the evolution of symptoms with age.

Keywords: AHDC1; Face2Gene; Xia-Gibbs syndrome; corpus callosum; tremor.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Agenesis of Corpus Callosum / genetics
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Child
  • DNA-Binding Proteins / genetics*
  • Democratic Republic of the Congo
  • Developmental Disabilities / genetics*
  • Exome Sequencing
  • Face / abnormalities
  • Frameshift Mutation*
  • Humans
  • Intellectual Disability / genetics*
  • Language Development Disorders / genetics
  • Male
  • Mitral Valve Insufficiency / genetics
  • Mitral Valve Insufficiency / surgery
  • Palate / abnormalities
  • Syndrome
  • Talipes Cavus / genetics

Substances

  • AHDC1 protein, human
  • DNA-Binding Proteins