Clinical report of a 17q12 microdeletion with additionally unreported clinical features.

Jennifer L. Roberts,Melissa Parra,Majed Dasouki,Ira Lu,Stephanie K. Gandomi,Chia-Ling Gau,Merlin G. Butler

doi:10.1155/2014/264947

Abstract

Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified a de novo suspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband's phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient's unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations.

Highlights

The 17q12 region contains copy number variations previously reported in association with a variety of clinical findings, most frequently renal cystic disease, maturity onset diabetes of the young type 5, pancreatic atrophy, Mullerian aplasia in females, and variable cognitive involvement [1,2,3,4,5,6]
Perhaps, the most widely reported feature resulting from the 17q12 deletion, while cognitive impairment and autism spectrum disorder have recently been associated with this deletion [2]
Deletion or mutation of HNF1B has been associated with renal cystic disease, diabetes mellitus, and liver, pancreas, and female genital tract abnormalities [2]

Summary

Introduction

The 17q12 region contains copy number variations previously reported in association with a variety of clinical findings, most frequently renal cystic disease, maturity onset diabetes of the young type 5, pancreatic atrophy, Mullerian aplasia in females, and variable cognitive involvement [1,2,3,4,5,6]. Perhaps, the most widely reported feature resulting from the 17q12 deletion, while cognitive impairment and autism spectrum disorder have recently been associated with this deletion [2]. Of 15,749 patients referred for developmental delay or autism spectrum disorder in their study, 18 patients (0.11%) were found to have a 17q12 deletion. Of these 18 patients, 9 were found to have in common a 1.4 Mb deletion [34,819,670–36,203,752 bp (hg19)]. Autism spectrum disorder was found in all six male patients studied. Other common features of these patients with 17q12 deletions included macrocephaly, mild facial dysmorphism, genitourinary tract abnormalities, renal cysts, and recurrent infections of the ear, upper respiratory system, and urinary tract

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Conclusion