Endocrine Abstracts

JOINT2329

Introduction: Several studies have investigated single endocrine manifestations of 22q11.2 Deletion Syndrome (22q11.2DS), however, data on the comprehensive endocrinological involvement in children and adults are currently scanty.

Aim: The present study addresses the broad spectrum of endocrine manifestations in 22q11.2DS across all age groups, investigating genotype-phenotype correlations and disease-onset, to refine follow-up strategies.

Materials and Methods: Retrospective cross-sectional study on 71 patients with 22q11.2DS. Clinical, biochemical and genetic data were retrieved from medical records.

Results: We included 71 patients (M/F 37/34; 38 children and 33 adults; median age 13.8, range 1.2-51.5 years). Endocrine manifestations were found in 32/71 patients (45.1%, 16 children and 16 adults). Hypocalcemia due to hypoparathyroidism was the most common feature (28/32 patients), with neonatal onset in 16/28 patients (57.1%), half of whom were symptomatic. Later-onset hypocalcemia occurred in 12 patients (7 children and 5 adults), all asymptomatic. Chronic hypoparathyroidism was present in 44% of patients with neonatal onset and 67% with later-onset, affecting globally 21% of patients. Thyroid dysfunction was observed in 12/71 patients (16.9%, 5 children, 7 adults), 11 with primary hypothyroidism and one with early-onset Graves’ disease; 2 euthyroid patients presented thyroid autoantibodies. Thyroid disease was significantly associated to hypoparathyroidism (8/28 vs 4/43 patients; P = 0.034). Short stature, reported in 20.8% of patients (23.7% of children, 15.2% of adults), was neither due to growth hormone deficiency nor linked to major comorbidities (palatal defects, infections, heart disease). Obesity was more prevalent in adults than children (27.3% vs 5.6%) and resulted associated with psychiatric disorders (P = 0.033) and their medications (P = 0.003), with 4.7-fold increased risk in psychiatric patients. The latest-onset endocrinopathy occurred at the age of 30 years. Most patients (46/55, 83.6%) had a classic deletion (CD, 2.5-3 Mb), 8 patients (14.5%) short deletion (<2.5 Mb) and one (1.8%) long deletion (>3 Mb). Hypoparathyroidism and hypothyroidism were more prevalent in CD patients (45.7% and 19.6%, respectively). However, no correlation was found between deletion length and endocrinopathies, whereas neonatal pathologies positively correlated with CD (P = 0.021).

Conclusions: This study provides the first comprehensive analysis of endocrinological involvement in pediatric and adult patients with 22q11.2DS, featuring all age groups. The most common conditions were hypoparathyroidism, hypothyroidism, and short stature. Our findings highlight the importance of monitoring patients at all ages and might suggest that check-ups frequency could be reasonably reduced after the age of 30 years for those without existing endocrinopathies.