Endocrine Abstracts

JOINT2172

Introduction: 3-M syndrome is a rare autosomal recessive disorder characterized by short stature, distinctive facial features, and skeletal abnormalities. Mutations in the CUL7, OBSL1, and CCDC8 genes are associated with this condition. Short stature in 3-M syndrome has been attributed to growth hormone (GH) resistance rather than GH deficiency. GH resistance has been linked to impaired protein scaffolding, transport dysfunction, and p53-mediated apoptosis in the IGF-1 post-receptor pathway. Here, we describe the growth trajectory of an Indian girl with 3-M syndrome undergoing recombinant GH therapy.

Case Report: A 4-year-old girl, born to non-consanguineous parents, was delivered at term with a low birth weight (2300 g; -2.25 SDS) and length (46 cm; -1.69 SDS). She experienced birth asphyxia and required neonatal intensive care for 13 days. Antenatal ultrasound at 34 weeks had raised the suspicion of skeletal dysplasia. At birth, she exhibited characteristic features of 3-M syndrome, including a broad, fleshy nose, anteverted nostrils, thick patulous lips, a square chin, curvilinear eyebrows without synophrys and a short thorax. Radiographic features included slender long bones with diaphyseal constriction and flared metaphyses. Vertebral bodies appeared tall with reduced anterior-posterior and transverse diameter and anterior wedging of the thoracic vertebral bodies. Her ribs appeared to be horizontal. Pelvic bones were small and the iliac wings appeared flared. She had a delayed bone age, A clinical diagnosis of 3-M syndrome was confirmed after genetic testing, which revealed a compound heterozygous class 1 and class 2 variation in the CUL7 gene. IGF-BP3 levels were normal. We did not perform a growth hormone stimulation test as she had a genetic diagnosis. Recombinant growth hormone therapy was initiated at 3 years of age, at a dose of 35 mg/kg/day. After 1 year of treatment, a height gain of 12 cm was observed, demonstrating a significant response to GH therapy.

Conclusion: This case highlights a notable height SDS increase over one year of follow-up in a child with 3-M syndrome receiving GH therapy. Clinicians should recognize the variability in GH response among individuals with 3-M syndrome and consider early intervention when appropriate.