RIN2 syndrome

RIN2 syndrome, also known as MACS syndrome (Macrocephaly, Alopecia, Cutis laxa, and Scoliosis), is an extremely rare autosomal recessive connective tissue disorder caused by biallelic mutations in the RIN2 gene. This gene encodes a protein involved in endosomal trafficking and regulation of vesicular transport, which plays a role in elastic fiber assembly and extracellular matrix homeostasis. The condition primarily affects the skin, skeletal system, and connective tissues. Key clinical features include macrocephaly (abnormally large head), generalized cutis laxa (loose, redundant, and inelastic skin), sparse hair or alopecia, progressive scoliosis or kyphoscoliosis, joint hypermobility, and distinctive facial features including a broad nasal bridge, downslanting palpebral fissures, and thick lips. Affected individuals may also exhibit soft, doughy skin texture, hernias, and mild developmental delay in some cases. The skin findings are particularly prominent on the face and trunk, giving an aged appearance. There is currently no specific or curative treatment for RIN2 syndrome. Management is supportive and symptomatic, focusing on orthopedic monitoring and intervention for scoliosis, dermatological care, and regular developmental assessments. Physical therapy may be beneficial for joint hypermobility. Genetic counseling is recommended for affected families. The condition was first described in a small number of families, and the total number of reported cases in the medical literature remains very limited.

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

Common questions about RIN2 syndrome