Unbalanced Translocation Affecting the Long Arms of Chromosome 10 and 22 Causes Complex Syndromes with Very Severe Neurodevelopmental Delay, Speech Impairment, Autistic Behavior, and Epilepsy

Background: Isolated abnormalities in terminal regions of chromosome 10q and 22q were rarely described in patients affected by neuropsychological impairment, abnormal facies, and heterogeneous structural abnormalities of the body. Chromosomes 10q and 22q harbor important genes, playing a major role in CNS development, like DOCK1 and SHANK3, and in overall body growth, like FGFR2 and HTRA1.

Methods: By using clinical, neuroradiological, neurophysiological, and genetic assessment, we studied three siblings affected by two different forms of very severe neuropsychological impairment with structural physical abnormalities, epilepsy, and body overgrowth.

Results: The genetic analysis revealed two different unbalanced translocations t(10;22)(q26.13;q13.32) of genetic material between the long arms of these two chromosomes, deriving from the maternal balanced translocation. Consequences of the unbalanced translocation were the simultaneous partial monosomy of 10q26.13 to 10qter and partial trisomy of 22q13.32 to 22qter in two patients and, respectively, the simultaneous trisomy distal q10 and monosomy distal q22 in one patient.

Conclusion: To the best of our knowledge, here we describe for the first time a causal association between unbalanced translocation t(10;22) affecting the long arms of both chromosomes, and a very severe neurodevelopmental delay in three siblings.