Chromosome Xp22.3 deletion syndrome with X-linked ichthyosis, Kallmann syndrome, short stature, generalized epilepsy, hearing loss, attention deficit hyperactivity disorder, and intellectual disability – A rare report with review of literature

Abstract

Chromosome Xp22.3 deletion syndrome is a very rare contiguous gene deletion syndrome with variable phenotype due to the deletion of genes from the distal short arm of the X chromosome (Xp), including the short-stature homeobox (SHOX), anosmin-1 (ANOS1), arylsulfatase (ARSL), neuroligin-4 (NLGN4), and steroid sulfatase (STS) genes. We have reviewed the available literature on the chromosome Xp22.3 deletion syndrome. A 10-year-old boy presented with global developmental delay, generalized epilepsy, decreased hearing, and hyperactivity. He had no significant family history. Examination revealed microcephaly, short stature, and dry and scaly skin lesions on the trunk. He had thick arched eyebrows, a depressed nasal bridge, a long philtrum, high arched palate, retrognathia, brachytelephalangy, brachymetatarsia, and mild scoliosis. Brainstem-evoked response audiometry testing revealed moderate hearing loss. Magnetic resonance imaging showed cerebellar tonsillar ectopia. Clinical exome sequencing revealed a likely pathogenic contiguous deletion (~8.10 Mb) spanning genomic location chrX:g.(_630898)_(8732037_)del encompassing ANOS1, ARSL, NLGN4X, SHOX, and STS genes. We have reviewed the available literature for reported associations of Chromosome Xp22.3 deletion syndrome and report a novel association of X-linked ichthyosis, Kallmann syndrome, global developmental delay, short stature, bilateral hearing loss, generalized epilepsy, attention deficit hyperactivity disorder, and intellectual disability.