Atelosteogenesis type I

Atelosteogenesis type I (AOI), also known as giant cell chondrodysplasia or spondylohumerofemoral hypoplasia, is a severe skeletal disorder characterized by incomplete bone formation (atelosteogenesis literally means 'incomplete bone formation'). It is caused by heterozygous mutations in the FLNB gene, which encodes filamin B, a protein critical for skeletal development. The condition is typically lethal in the perinatal period due to severe pulmonary hypoplasia. Atelosteogenesis type I primarily affects the skeletal system, resulting in severely shortened limbs (micromelia), dislocated elbows, knees, and hips, distinctive hand and foot abnormalities including hitchhiker thumbs, and marked underdevelopment of the vertebral bodies and long bones. Characteristic radiographic findings include absent or severely hypoplastic humeri and femora, coronal vertebral clefts, and distinctive multinucleated giant cells in cartilage on histological examination. Affected infants also frequently exhibit midface hypoplasia, cleft palate, micrognathia, and a narrow thorax contributing to respiratory insufficiency. There is currently no curative treatment for atelosteogenesis type I. Management is supportive and focused on respiratory care, though the condition is almost invariably fatal at or shortly after birth. Genetic counseling is important for affected families, as the condition arises from de novo dominant mutations in most cases. Prenatal diagnosis may be possible through ultrasound detection of skeletal abnormalities and molecular genetic testing.

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

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