Growth Hormone Deficiency (GHD) in a Child with Chromosome 7q11.23 Duplication: Consequence or Co-Incidence

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

Poster Board SAT-635
Kanthi Bangalore Krishna*1, Melissa Anne Buryk2, Urvashi Surti3 and Mark A Sperling4
1Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 2Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 3Magee Women's Hospital, University of Pittsburgh, 4Children's Hospital of Pittsburgh, Pittsburgh, PA
Background:  Chromosome 7q11.23 micro-duplication is a newly described recognizable phenotype.1 Although the reciprocal micro-deletion gives rise to Williams syndrome, with its characteristic features, the phenotype of the duplication is quite different. Typical features include distinctive facial dysmorphism, speech delay, behavioral disorders, congenital anomalies and/or neonatal hypotonia. Whereas short stature is occasionally described, GHD has previously not been reported in this syndrome. We report a child with a genetic diagnosis of Chromosome 7q11.23 micro-duplication, diagnosed with GHD and with appropriate response to GH treatment.

Clinical Case: The ten year old female presented for evaluation of short stature. Her history was significant for autism and speech delay as well as dysmorphic facial features. Two of three siblings had similar clinical features (facial features, speech delay, behavior disorders) and one of those had short stature as well as cleft palate and micropenis. Both parents have significant intellectual disability.  Auxology revealed a height at -2.86 Z scores below age standards, with weight at the 15th percentile. Facial features included; broad forehead, thin lips and a short philtrum. The limbs were proportionate.

Laboratory evaluation showed a serum IGF-1 of 112 ng/mL (normal 261-1086), with normal thyroid functions. Provocative testing with arginine-insulin elicited a peak GH response of 5.3ng/ml (normal >10ng/ml) at the time of hypoglycemia (glucose: 17mg/dl) consistent with GHD. Brain MRI showed a normal adenohypophysis and pituitary stalk with a small Rathke’s cleft cyst in the neurohypophysis. Bone age was delayed by 4 SDS (5 year 9 month at 10 years). GH replacement therapy (0.3mg/kg/week) resulted in improved growth velocity of > 6 cm/year (c.f. < 3cm/yr previously). Her younger male sibling with similar facial features, short stature, micropenis and cleft palate was found to carry the same chromosomal duplication.

Conclusion:  Growth hormone deficiency, not previously reported in patients with 7q11.23 micro duplication, and likely related to the Rathke’s cleft cyst is documented. The facial characteristics in this syndrome suggest abnormalities in midline fusion with Rathkes cyst in one subject and cleft palate in the other. These midline defects suggest that GHD is not co-incidental but may be causally related emphasizing the importance of evaluating growth hormone secretion in patients with this syndrome.

1. Dixit A, McKee S, Mansour S, Mehta S, Tanteles G, Anastasiadou V, Patsalis P, Martin K, McCullough S, Suri M, Sarkar A. 7q11.23 Microduplication: a recognizable phenotype. Clin Genet. 2013: 83(2):155-161.

Nothing to Disclose: KB, MAB, US, MAS

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