Deep phenotyping in 1p36 deletion syndrome

Purpose: Although 1p36 deletion syndrome is the most common terminal deletion syndrome, un-explained phenotypic variability still occurs. We aimed to delineate the phenotype of this syndrome in detail and to characterize the phenotype-genotype correlation. Methods: We retrospectively reviewed 15 patients diagnosed with 1p36 deletion syndrome confirmed by chromosomal microarray. Results: All 15 patients revealed delayed attainment of motor milestones and speech. Seven patients (46.7%) never walked alone and only two (13.3%) could express a simple two-word sen-tence. They all showed subsequent intellectual disability. Two patients with large deletions of both distal and proximal critical regions of the 1p36 region shared severe intellectual disability with Rett syndrome-like behavioral features. Seizures, although frequent (73.3%), were well-con-trolled except in one patient with infantile spasms. Facial dysmorphism (92.9%) and ventricular mild dilatation with corpus callosum anomaly (46.7%) were common. Heart problems were identified in 14 patients, including structural abnormalities and/or functional problems associated with the gene encoding PR domain-containing protein 16. Two patients developed severe cardiac dysfunction requiring heart transplantation in their late teens. One patient with a 400 Kb deletion partly overlapping with the gene encoding calmodulin-binding transcription activator 1 did not have facial dysmorphism and presented with mild developmental delay and ataxic gait. One patient had a choledochal cyst, which was resected due to neonatal cholestasis. Conclusion: Although the phenotype of 1p36 deletion syndrome is quite consistent with previous reports, additional manifestations such as certain behavioral features, ataxic gait, and severe cardiac dysfunction at an early age should be considered.