ABSTRACT
BACKGROUND: Cerebellar vermis hypoplasia has been associated with a large number of chromosomal abnormalities and metabolic disorders, with few candidate genes clearly linked to isolated cerebellar vermis hypoplasia. PATIENT DESCRIPTION: We describe on a 12-year-old boy with inferior vermian hypoplasia associated with a novel de novo microdeletion. He presented with intellectual, speech and language impairment, unilateral facial nerve weakness, marked constipation, and bilateral hand and foot anomalies that were not consistent with any previously described syndrome. His hand features were digital reductions similar to those seen in 4q34 deletion syndrome, known as the "tale of the nail" sign. Cranial magnetic resonance imaging demonstrated isolated inferior cerebellar vermis hypoplasia. RESULTS: A de novo 1.4 Mb interstitial deletion was identified at 8q13.1-q13.2 on chromosomal microarray. This copy number variant involves 18 human genome reference sequence genes, with 11 Mendelian Inheritance in Man genes. Homozygous mutations in one of these genes (CSPP1) has recently been recently described as causing Joubert syndrome. CONCLUSION: We propose that the constellation of clinical features in this child represents a novel microdeletion syndrome and hypothesize that CSPP1 or other genes within the deleted region contribute to the cerebellar development.