RAPADILINO syndrome

RAPADILINO syndrome is an extremely rare autosomal recessive disorder caused by biallelic mutations in the RECQL4 gene, which encodes a DNA helicase important for genome stability. The name RAPADILINO is an acronym derived from its key clinical features: RAdial hypoplasia/aplasia, PAtellae hypoplasia/aplasia and cleft or highly arched PAlate, DIarrhea and DIslocated joints, LIttle size (short stature) and limb malformation, NOse slender and NOrmal intelligence. The syndrome predominantly affects the skeletal system, with characteristic radial ray defects, absent or underdeveloped kneecaps, joint hypermobility or dislocations, and significant growth restriction leading to short stature. Gastrointestinal symptoms, particularly chronic diarrhea in infancy, are also commonly reported. Craniofacial features include a slender nose and a cleft or highly arched palate. RAPADILINO syndrome belongs to a group of RECQL4-related disorders that also includes Rothmund-Thomson syndrome and Baller-Gerold syndrome. Unlike Rothmund-Thomson syndrome, RAPADILINO syndrome typically does not present with the characteristic skin rash (poikiloderma). However, patients with RAPADILINO syndrome have an increased predisposition to malignancies, particularly osteosarcoma and lymphoma, which necessitates long-term cancer surveillance. The majority of reported cases have been identified in Finland, suggesting a founder effect in the Finnish population. There is currently no cure or specific targeted therapy for RAPADILINO syndrome. Management is supportive and multidisciplinary, involving orthopedic interventions for skeletal abnormalities, nutritional support for feeding difficulties and diarrhea, and regular oncological screening for early detection of malignancies. Surgical correction may be required for palatal defects and limb malformations. Genetic counseling is recommended for affected families.

Common questions about RAPADILINO syndrome