Homozygous deletion of 21q22.2 in a patient with hypotonia, developmental delay, cortical visual impairment, and retinopathy

Am J Med Genet A. 2021 Feb;185(2):555-560. doi: 10.1002/ajmg.a.61969. Epub 2020 Nov 10.

Abstract

21q22 contains several dosage sensitive genes that are important in neurocognitive development. Determining impacts of gene dosage alterations in this region can be useful in establishing contributions of these genes to human development and disease. We describe a 15-month-old girl with a 1,140 kb homozygous deletion in the Down Syndrome Critical Region at 21q22.2 including 4 genes; B3GALT5, IGSF5, PCP4, DSCAM, and a microRNA (MIR4760). Clinical singleton genome sequencing did not report any candidate gene variants for the patient's phenotype. She presented with hypotonia, global developmental delay, cortical visual impairment, and mild facial dysmorphism. Ophthalmological exam was suggestive of retinopathy. We propose that the absence of DSCAM and PCP4 may contribute to the patient's neurological and retinal phenotype, while the role of absent B3GALT5 and IGSF5 in her presentation remain unclear at this time.

Keywords: chromosome 21; cortical visual impairment; developmental delay; homozygous deletion; hypotonia; retinopathy.

Publication types

  • Case Reports

MeSH terms

  • Chromosome Deletion
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21 / genetics
  • Comparative Genomic Hybridization
  • Developmental Disabilities / complications
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Down Syndrome / genetics
  • Down Syndrome / pathology
  • Female
  • Homozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / pathology
  • Phenotype
  • Retinal Diseases / genetics*
  • Vision Disorders / complications
  • Vision Disorders / genetics*
  • Vision Disorders / pathology

Supplementary concepts

  • Down Syndrome Critical Region