Endocrine Abstracts

JOINT3875

Background: Geleophysic dysplasia is a progressive skeletal disorder that mimics lysosomal storage diseases. It is characterized by short stature, brachydactyly, progressive joint contractures, distinctive facial features (including a "happy face" with full cheeks, hypertelorism, and a prominent philtrum), progressive cardiac valvular disease, and thickened skin. Intellectual development remains normal. The disorder is inherited in an autosomal recessive manner when caused by biallelic pathogenic variants in ADAMTSL2 or in an autosomal dominant manner when caused by heterozygous pathogenic variants in FBN1 or LTBP3.

Case Presentation: We report a case series of three Palestinian sisters and their cousin, all born to consanguineous parents, presenting with short stature, brachydactyly, lordosis, and delayed bone age. Initially diagnosed with idiopathic short stature, they were treated with growth hormone (GH). Whole-exome sequencing confirmed a homozygous c.475C>T (p.Arg159Trp) variant in ADAMTSL2, resulting in abnormal protein translocation.

• Patient 1 (20 years old): Final height 148 cm (-2.4 SD); received GH for 2 years, discontinued at bone age 14 years.

• Patient 2 (15 years, 10 mon old): Final height 150.2 cm (-1.7 SD), completed puberty; received GH for 4 years until bone age 13 years, 6 months.

• Patient 3 (10 years, 4 mon old): Current height -2.4 SD; received GH from bone age 5 years to 10 years, with height increasing from 106 cm to 124 cm. Echocardiography revealed mild aortic stenosis.

• Cousin (12.5 years old): Height -3.5 SD, mid-puberty, with delayed bone age (by 1.5 years). Did not receive GH and underwent bicuspid aortic valve repair for severe stenosis.

Conclusion: Despite GH treatment, the three sisters exhibited growth patterns inconsistent with expected parental height, and the youngest demonstrated similar growth velocity before and after GH discontinuation. Their cousin, who did not receive GH, exhibited a similar phenotype. These findings suggest that GH therapy had no significant impact on final height in individuals with ADAMTSL2-related geleophysic dysplasia, emphasizing the need for alternative management approaches.