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

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.

Homozygous 22q11.2 distal type II microdeletion is associated with syndromic neurodevelopmental delay

“…[MIM 607100] leading to nephronophthisis or Joubert syndrome (Parisi et al, 2004;Saunier et al, 2000), a homozygous deletion in 15q24.1 including CYP1A1 and EDC3 (Zhang et al, 2021), and a homozygous deletion of 21q22.2 in a child with global developmental delay, hypotonia, cortical visual impairment, and mild craniofacial anomalies (Hildebrandt et al, 2021).…”

“…Reasons for this may include pathogenicity of the heterozygous CNV with reduced reproduction rates, or embryonic lethality when multiple genes are deleted. Examples of such rarely reported homozygous deletions involving multiple genes to include the recurrent NAHR‐mediated deletion including NPHP1 [MIM 607100] leading to nephronophthisis or Joubert syndrome (Parisi et al, 2004; Saunier et al, 2000), a homozygous deletion in 15q24.1 including CYP1A1 and EDC3 (Zhang et al, 2021), and a homozygous deletion of 21q22.2 in a child with global developmental delay, hypotonia, cortical visual impairment, and mild craniofacial anomalies (Hildebrandt et al, 2021).…”