Lenz-Majewski hyperostotic dwarfism

Lenz-Majewski hyperostotic dwarfism is an extremely rare condition characterized by dwarfism, a distinctive facial appearance, cutis laxa, and progressive bone sclerosis. It is caused by mutations in the PTDSS1 gene, which plays a role in phospholipid synthesis. The condition is sporadic and inherited in an autosomal dominant pattern, typically presenting in early childhood with marked skeletal and neurodevelopmental findings. It is very rare, affecting fewer than 1 in 1 million individuals.

Individuals with Lenz-Majewski hyperostotic dwarfism exhibit a range of characteristic skeletal anomalies including broad clavicles, proximal symphalangism of the hands, a prominent and broad forehead, and broad ribs. Consistently observed features also include cutaneous finger syndactyly, joint hypermobility, delayed skeletal maturation, and cutis laxa. Intellectual disability, a key neurodevelopmental feature of the condition, is always present along with findings such as macrotia, sparse hair, enamel hypoplasia, and delayed cranial suture closure. Not all individuals experience every feature, and severity varies considerably.

Lenz-Majewski hyperostotic dwarfism results from mutations in the PTDSS1 gene, which encodes an enzyme involved in phospholipid synthesis. The condition is inherited in a sporadic, autosomal dominant manner, meaning that a single altered copy of the gene can lead to the clinical manifestations. Because the mutation typically arises de novo, there is usually no family history, although affected individuals may pass the variant to their offspring. Variable expressivity is common, and the severity and constellation of symptoms can differ even among individuals with the same genetic change.

Currently, management focuses on supportive care and symptom management since there are no FDA-approved treatments specifically for Lenz-Majewski hyperostotic dwarfism. Treatment is individualized and typically involves a multidisciplinary team to address both skeletal abnormalities and neurodevelopmental challenges. Regular surveillance is an essential part of long-term management, helping to detect potential complications early and adjust interventions as needed. Genetic counseling is recommended for affected individuals and their families to discuss the implications of the condition and options for family planning.

The long-term outlook for individuals with Lenz-Majewski hyperostotic dwarfism varies widely, with outcomes depending on the severity of both skeletal and neurodevelopmental manifestations. Although the condition is lifelong, current standards of supportive care can help manage symptoms and improve quality of life, allowing many individuals to reach adulthood. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for ongoing guidance.