BACKGROUND
High-density single-nucleotide comparative genomic hybridization (HD CGH-SNP) microarrays have improved the detection of copy number variants (CNVs) in dosage-sensitive chromosomal regions. Haploinsufficiency of the NSD1 gene at the 5q35 locus causes Sotos syndrome, marked by overgrowth, macrocephaly, and neurodevelopmental delay. Conversely, the reciprocal 5q35 microduplication, termed “reverse Sotos syndrome”, is an uncommon genomic entity with phenotypic variability that can lead to delayed clinical recognition in general pediatric and endocrine settings.
CASE REPORT
We report the case of a 5-year-old boy evaluated for persistent proportionate short stature (height 96.7 cm, standard deviation score [SDS] -2.28; weight 14.0 kg, SDS -2.15) and microcephaly (head circumference 47.0 cm, SDS -3.33) with delayed bone age (3.5 years at chronological age 5.0). Physical examination revealed trigonocephaly, a long nose, a small mouth with a thin upper lip, and xerosis. Neurodevelopmental assessment demonstrated global developmental delay, language delay, and attention deficit. Cranial computed tomography at age 5 years confirmed trigonocephaly with reduced ventricular dimensions and closed metopic suture. High-density array analysis (CytoScan HD) identified a de novo 1.87 Mb pathogenic gain at 5q35.2-q35.3 encompassing 29 OMIM genes, including NSD1. Post-diagnostic multidisciplinary management and genetic counseling (confirming low recurrence risk) were initiated.
CONCLUSIONS
This report documents a novel de novo 5q35.2-q35.3 microduplication with defined genomic breakpoints identified through a pediatric short-stature referral. The case reinforces the diagnostic importance of chromosomal microarray testing in children presenting with proportionate growth failure, microcephaly, and developmental delay, illustrating the opposite growth pattern to classic Sotos syndrome.

Keywords: Sotos Syndrome; Intellectual Disability; Genetic Techniques; Haploinsufficiency