A de novo 1.4‐Mb deletion at 21q22.11 in a boy with developmental delay

Abstract

Monosomy 21 is a very rare chromosomal abnormality. At least 45 patients with partial deletion involving 21q11 have been reported. Here, we report a Japanese boy who presented with pre- and postnatal growth delays, psychomotor developmental delay, microcephaly, and iris coloboma. Cytogenetic analysis revealed a de novo 1.4-Mb deletion at 21q22.11 containing 19 protein-coding RefSeq genes. We compared the clinical phenotypes between the present patient and 16 previously reported patients with a deleted region associated with postnatal growth delay and psychomotor developmental delay. Interestingly, ITSN1 was the only gene deleted or disrupted in all cases; this gene is known to be associated with intellectual disability. Microcephaly and brain structural abnormalities including polymicrogyria and agenesis/hypoplasia of the corpus callosum may also result from haploinsufficiency of ITSN1, highlighting its clinical significance for the neurological features of patients with monosomy 21.

Jacobsen syndrome, Braddock–Carey syndrome, and Beyond: Reflections on intellectual disability accompanied with thrombocytopenia

“…Intellectual disability accompanied by microcephaly in this patient could be attributable to haploinsufficiency of DYRK1A [Fujita et al, ]. Similar observations have been documented in a larger cohort of patients [Fukai et al, ]. Recently, we encountered a patient with intellectual disability, cardiac disease, and dysmorphic facial features.…”

Establishing SON in 21q22.11 as a cause a new syndromic form of intellectual disability: Possible contribution to Braddock–Carey syndrome phenotype

“…There is a debate on the causative gene that is responsible for the developmental delay observed in the microdeletion syndrome in 21q22 (Table ). Using the classic approach of exclusion and inclusion mapping of microarray data, Fukai et al [] proposed that ITSN1 is responsible for the developmental delay. However, it remains unclear if other flanking genes also contribute to the developmental delay.…”

Double deletion of a chromosome 21 inserted in a chromosome 22 in an azoospermic patient

“…In fact, the severity of the phenotype described by Lyle et al in this proximal centromere-32.3 Mb region is probably caused by the deletion of band 21q22 in two out of three patients, corresponding to the description of "monosomy 21q syndrome" [19]. The latest described patient carrying a 21q22 deletion is a 19-month-old child with a global developmental delay, dysmorphic features, and cardiac and neurological malformations [6]. Deletion of the more distal segment of 21q is the most common 21q deletion and is not responsible for severe phenotypes and intellectual deficiency according to the division of chromosome 21 by Lyle et al [13], in agreement with other described cases.…”