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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. usc Refereed/Peer-reviewed

Aim This study aimed to determine the utilisation, yield and cost of screening genetic investigations in a sample of children diagnosed with pervasive developmental disorders (PDD; DSM-IV). The purpose was to inform development of strategies for genetic investigation of children with these disorders. Methods 699 patients with PDD were identified, and genetic investigations evaluated. A sub-group of 219 patients underwent clinical chart audit, and the resulting clinical characteristics evaluated in the context of investigation use and findings. Results 24.8%, 15.9% and 25.1% of the clinic population had undergone investigation with chromosomal microarray (CMA), karyotype (KT) and fragile X testing, respectively. CMA is associated with a cost reduction of $3437 less per diagnosis compared with KT (p = 0.026). Several characteristics were associated with increased odds of a significant CMA finding, most significant of which was comorbid epilepsy (odds ratio 10.4; p Discussion CMA appears to increase the diagnostic yield of screening genetic investigations in PDD. This finding is consistent with what has been seen in other populations internationally. CMA reduces cost per incremental diagnosis with comparison to KT, amongst children with PDD. Epilepsy was found to be a significant predictor of a pathogenic finding on chromosomal microarray.