Lenz-Majewski hyperostotic dysplasia

Lenz-Majewski hyperostotic dysplasia (also known as Lenz-Majewski hyperostotic dwarfism or Lenz-Majewski syndrome) is an extremely rare genetic disorder characterized by progressive skeletal sclerosis (increased bone density), intellectual disability, and distinctive craniofacial and limb abnormalities. The condition affects multiple body systems, most prominently the skeletal system, skin, and central nervous system. Key skeletal features include progressive hyperostosis (excessive bone growth) affecting the skull, vertebrae, and diaphyses of long bones, broad and dysplastic clavicles, and brachydactyly (short fingers) with cutaneous syndactyly (webbing of the skin between fingers and toes). Craniofacial features include a large cranium with widely open fontanelles, prominent forehead, hypertelorism (widely spaced eyes), and choanal atresia or stenosis in some cases. Affected individuals typically present at birth or in early infancy with a progeroid (aged) appearance, loose and wrinkled skin (cutis laxa), and failure to thrive. Enamel hypoplasia of the teeth, proximal symphalangism (fusion of finger joints), and delayed developmental milestones with intellectual disability are commonly observed. Growth retardation leading to short stature is a hallmark of the condition. Some patients may also have hearing loss and genitourinary anomalies. Lenz-Majewski hyperostotic dysplasia is caused by gain-of-function mutations in the PTDSS1 gene, which encodes phosphatidylserine synthase 1, an enzyme involved in phospholipid metabolism. The condition arises from de novo (new) dominant mutations. There is currently no cure or disease-specific treatment for this condition. Management is supportive and symptomatic, involving a multidisciplinary team that may include orthopedic specialists, developmental therapists, dermatologists, and other specialists to address the various manifestations of the disease.

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