Cenani-Lenz syndrome

Cenani-Lenz syndrome (CLS), also known as Cenani-Lenz syndactyly or Cenani syndactylism, is a rare autosomal recessive skeletal disorder primarily affecting the limbs. It was first described by Cenani and Lenz in 1967. The hallmark of this condition is severe syndactyly (fusion of the fingers and toes), which can range from total fusion of all digits to a mitten-like appearance of the hands and feet. The bones of the hands and feet are often disorganized, with synostosis (bony fusion) of the carpal, metacarpal, tarsal, and metatarsal bones, resulting in a characteristic radiographic appearance of oligodactyly or a shapeless mass of fused bones. The forearms may also be affected, with radioulnar synostosis being a common finding. Lower limbs can show similar but sometimes milder involvement. Beyond the limbs, some patients may exhibit additional skeletal anomalies including short stature and, less commonly, renal malformations such as unilateral renal agenesis or other kidney anomalies. Intelligence is typically normal. The syndrome is caused by homozygous or compound heterozygous mutations in the LRP4 gene (low-density lipoprotein receptor-related protein 4) on chromosome 11p11.2, which plays a critical role in limb development and Wnt signaling pathways. Some cases have also been linked to mutations in the GREM1 gene (encoding Gremlin 1), a BMP antagonist involved in limb patterning. There is no cure for Cenani-Lenz syndrome. Management is primarily supportive and surgical, focusing on improving hand and foot function through reconstructive orthopedic surgery to separate fused digits where feasible. Occupational therapy may help optimize hand function. Renal anomalies, when present, should be monitored and managed appropriately. Genetic counseling is recommended for affected families to discuss recurrence risks and family planning options.

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