3M syndrome

3M syndrome is a rare autosomal recessive growth disorder named after the initials of the three researchers who first described it: Miller, McKusick, and Malvaux. It is characterized by severe pre- and postnatal growth restriction (short stature), with affected individuals typically reaching an adult height well below the normal range, often under 120 cm (approximately 4 feet). Importantly, intelligence is usually normal. The condition primarily affects the skeletal system and is associated with distinctive facial features including a triangular face, frontal bossing, a fleshy nasal tip, long philtrum, full lips, and pointed chin. Skeletal abnormalities are prominent and include slender long bones, tall vertebral bodies, short thorax, and delayed bone age. Other features may include clinodactyly (curved fifth fingers), short fifth fingers, prominent heels, and loose joints. 3M syndrome is caused by pathogenic variants in one of several genes involved in growth regulation: CUL7 (3M syndrome type 1), OBSL1 (3M syndrome type 2), and CCDC8 (3M syndrome type 3). These genes encode proteins that participate in a shared molecular pathway important for normal growth. Diagnosis is based on clinical features, radiographic findings, and molecular genetic testing. There is currently no specific cure for 3M syndrome. Growth hormone therapy has been attempted in some patients but generally shows limited effectiveness in significantly improving final adult height. Management is primarily supportive and involves monitoring growth, addressing any orthopedic complications, and providing genetic counseling to affected families. Regular follow-up with a multidisciplinary team including endocrinologists, orthopedic specialists, and clinical geneticists is recommended.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about 3M syndrome