We report a case of an atypical 22q11 deletion, undiagnosed by conventional cytogenetic techniques, supporting the diagnostic power of array-CGH. The patient was born from healthy, unrelated parents. Family history and pregnancy were unremarkable. He was born at term by spontaneous delivery. Neonatal auxologic parameters were within normal limits. He was referred to our service at 2 months of age for failure to thrive associated with a large ventricular septal defect. Ogival palate with submucosal cleft were noted. Standard karyotype and FISH analysis for DiGeorge syndrome were negative. At the age of 5 months, developmental delay associated with microcephaly, plagiocephaly, type1 trigonocephaly and mild ocular proptosis became evident. Neuroimaging scans showed craniosynostosis due to early elision of the left lambdoid and metopic sutures, resulting in a rare case of synostotic posterior plagiocephaly. Molecular analysis of FGFR2, FGFR3 e TWIST genes was negative for mutations. A-CGH demonstrated 3 genomic imbalances: del22q11.2 (772-853 Kb) de novo, and 2 duplications of maternal origin , dup2q21.2q21.3 and dup9q33.3. The pathogenetic deletion is nested in the distal region of the typical 22q11 3 Mb deletion, including 23 genes, 12 of which with unknown function. SCARF2, the causative gene of Van den Ende-Gupta syndrome, characterized by several skeletal anomalies, including craniosynostosis, maps to the deleted region. As known skeletal malformations are found in 34% of patients affected by del22q11, rarely with craniosynostosis. We suggest that SCARF2 may be responsible for plagiocephaly in our patient and play a role in the pathogenesis of the del22q skeletal abnormalities.
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