Extreme familial short stature in a novel variant of a duplication syndrome located within the Williams-Beuren-critical-region

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 632-648-Pediatric Growth Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-632
Ursula Kuhnle*1, Jana Pricelius2, Claudia Nevinny-Stickel-Hinzpeter2 and Stefanie Bug2
1Inst for Child & Adolescent Health, Munich, Germany, 2synlab MVZ Humane Genetik, Munich, Germany
We report a 1 year 6 months old girl with proportionate short stature (74 cm, -3,7 SDS), normal developmental milestones and discrete dysmorphic facial features. Birth weight was 3500g and length was 49 cm at a gestational age of 38 weeks, thus well within the normal range, but the mother had noted extremely tiny hands and feet in her newborn child. The 32 year old mother was with 142 cm (-4,6 SDS) also very short, with somewhat similar discrete dysmorphic features and normal intelligence. She is a University graduate. On history her father, who had left the family, was also extremely short, around 150 cm, but he was not available for further studies.

Using high resolution based comparative genomic hybridization (SurePrint G3 CGH microarray 4x180K, AGilent Technologies, USA) a gain of 1 million base pairs (1Mb) within the Williams-Beuren critical region (WBCR) in 7q11.23 was revealed. Interestingly, however, only half of the region typically gained in the WBCR-syndrome was duplicated. The proximal border of the interval mapped to the Elastin gene (ELN), indicating that only the distal part of the commonly duplicated region was affected. The identical copy number change was identified in the mother.

Thus, we have identified a novel familial duplication syndrome which represents a novel atypical variant of the classical WBCR-duplication syndrome. The phenotype shows mild facial dysmorphic features extreme short stature and absence of cognitive impairment, speech disorders or autism, frequently reported in classical Williams-Beuren-syndrome. In contrast, short stature is rarely associated with the typical Williams-Beuren syndrome. Genotype-phenotype correlation in the WBCR-duplication syndrome is still ongoing and difficult due to the high phenotypic variability and incomplete penetrance of most symptoms. The presenting symptom in our family is "short stature", but the responsible gene(s) is not yet identified. To know more about genes causing short stature might help to better understand also other forms of familial short stature and might help to decide what sort of therapy might be useful. Further studies are needed to answer this question.

Nothing to Disclose: UK, JP, CN, SB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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