Endocrine Abstracts

JOINT945

Background: Skeletal ciliopathies are a rare group of disorders affecting bone development. Short rib dysplasia is characterized by a narrow thorax, shortened ribs, and variable metaphyseal abnormalities. This report presents a child with a confirmed genetic diagnosis of KIAA0753-related skeletal ciliopathy and highlights diagnostic and therapeutic challenges.

Case Presentation: A 4-year-old Yamni boy was evaluated for short stature at 5 months, having normal birth parameters but falling below the 3rd centile in height by 5 months. He exhibited facial dysmorphism, short long bones, and a narrow thorax, though BMI and development were normal. His parents were first cousins with no family history of similar conditions. Genetic testing identified a homozygous pathogenic variant in KIAA0753, confirming short rib dysplasia, an autosomal recessive disorder associated with skeletal dysplasia and Joubert syndrome features. At 1 year, he developed severe obstructive sleep apnea (OSA) and underwent adenotonsillectomy at 14 months. By 23 months, his height was -4 SD, and growth velocity was 7 cm/year. GH stimulation testing revealed a peak GH level of 19 ng/ml. A GH trial (0.05 mg/kg/day) was initiated at 2 years, leading to a height improvement of 1.4 SD over 2.5 years, reaching -2.6 SD with normal growth velocity.

Management and Outcome: The patient continues GH therapy with ongoing height improvement and no side effects. His latest anthropometric data at 4 years showed a height SDS of -2.6, weight SDS of -1.08, and IGF-1 level of 201 mg/L (2 SD).

Discussion: Genetic evaluation is essential in cases of disproportionate short stature. GH therapy in skeletal dysplasias has shown variable efficacy. Kochar & Chugh (2020) reported modest height gains in achondroplasia and hypochondroplasia (Kochar & Chugh, 2020). Upadhyay et al. (2022) noted that GH therapy might exacerbate skeletal abnormalities in Dyggve–Melchior–Clausen syndrome (Upadhyay et al., 2022). Despite uncertainties, our case supports potential GH benefits in skeletal ciliopathies.

Conclusion: Early diagnosis, genetic testing, and individualized GH therapy may optimize outcomes in skeletal ciliopathies. Continued GH therapy is recommended until the final adult height is reached, though further research is needed to refine treatment protocols.

Keywords: Skeletal Ciliopathy, Short Rib Dysplasia, KIAA0753, Growth Hormone Therapy, Rare Genetic Disorders