ESPE Abstracts

Introduction: The 22q11 deletion is one of the most commonly recognized deletion syndromes in humans (~ 1/4000 live births). Most of the reported defect generally involves a deletion at breakpoints LCR22A and LCR22D causing DiGeorge or velo-cardio-facial syndrome. In deletion syndromes, the phenotype ranges from unspecified dysmorphic features to severe cognitive/behavioral deficits, but normal features can occur depending on the size and amount of gene dosage. We are reporting a case of interstitial deletion within 22q11.21, and its response to growth hormone therapy.

Case Presentation: A 7 years old male boy, presented to the pediatric endocrinology clinic for assessment of short stature. He was born at term, with a birth weight: of 3.1 kg and a length of 48 cm. He had no history of chronic illnesses or previous hospitalization. His development was normal for his age. His weight SDS (WAZ): -0.9, height SDS (HAZ):- 2, BMISDS: 0.65, mid-parenteral height SDS (MPHTSDS): +1.2, and growth velocity: 4.7cm/yr. Clinical examination revealed: subtle dysmorphic features, broad thumb, and mild pectus carinatum, with normal heart and abdominal examination and normal pre-pubertal genitalia. Investigations showed normal hemogram, and renal and liver profiles. Insulin-like growth factor: 49.5 mg/L (-2 SD). The clonidine stimulation test revealed a normal Growth hormone peak (13.9 mg/L). He had normal thyroid function and calcium homeostasis. His bone age corresponded to his chronological age. Microarray analysis revealed an interstitial deletion of *356-kb within cytogenetic band 22q11.21, the deleted segment includes the PRODH gene. A trial of growth hormone therapy (0.05 mg /kg/day) for 2 years increased his IGF1 to 102 (-0.2 SD), enhanced his growth velocity to 8 cm and 6.5 cm per year respectively, and increased HtSDS to -1.37 and BMISD to 0.

Discussion: This case revealed that interstitial deletion within 22q11.21 is associated with significant short stature compared to MPHTSDS (-3SD) with normal GH release after provocation but significantly low IGF1. The significant effect on final adult height appears to arise from reduced gene dosage.

Conclusion: We are reporting linear growth impairment in a child carrying an interstitial deletion of 356-Kb within cytogenetic band 22q11.21. with low IGF1 level and normal GH response to provocation. High-resolution microarray testing should be recommended in children who present with HtSDS < -2 from their MPHtSDS especially those with subtle dysmorphism.