atelosteogenesis type I

Atelosteogenesis type I is a severe, multi-system skeletal dysplasia that disrupts normal bone and cartilage development, resulting in profound short-limbed dwarfism and multiple joint dislocations. The condition stems from disease-causing changes in the FLNB gene, which encodes filamin B, a protein critical for arranging the cellular scaffolding that shapes growing bones. Signs are usually evident on prenatal ultrasound or immediately after birth, and the condition affects individuals of any sex. It is exceedingly uncommon, with fewer than one in a million people thought to be affected worldwide. Because of its severity, families often meet specialists soon after a prenatal or newborn diagnosis.

The hallmark of atelosteogenesis type I is marked shortening of the arms and legs accompanied by widespread joint dislocations, especially at the elbows, knees, and ankles. Craniofacial findings such as a depressed nasal bridge, micrognathia (small lower jaw), hypertelorism (widely spaced eyes), and low-set ears give the face a characteristic appearance. The chest is typically bell-shaped and underdeveloped, and the clavicles appear unusually long on imaging, both of which can compromise breathing. Skeletal surveys show coronal clefting of the vertebrae, vertebral hypoplasia, and absence or severe shortening of the fibulae. Club feet (talipes) and generalized limb undergrowth are also consistently reported. Not all individuals experience all possible complications, and the severity and specific combination of features vary considerably among affected pregnancies and newborns.

Atelosteogenesis type I results from pathogenic variants in the FLNB gene. Filamin B helps link the internal actin cytoskeleton to signaling pathways that guide cartilage maturation and bone formation, so variants that disrupt its structure alter skeletal development. The condition follows an autosomal dominant inheritance pattern, meaning a single altered copy of FLNB can cause disease. However, nearly all reported cases are sporadic, arising for the first time in the affected child rather than being inherited from a parent. When a variant occurs de novo, the chance that unaffected parents will have another child with the condition is very low, although recurrence through germline mosaicism cannot be ruled out completely. If an individual with a pathogenic FLNB variant were to survive to reproductive age, each pregnancy would carry a 50 percent chance of passing on the variant. Genetic counseling is recommended for all families to review test results, discuss recurrence risk, and explore reproductive options.

Currently, there are no disease-modifying therapies for atelosteogenesis type I, so management focuses on supportive care tailored to each child’s needs. Newborns often require immediate attention from a multidisciplinary team that may include neonatology, orthopedics, pulmonology, and clinical genetics to address respiratory compromise due to the small, rigid chest and to plan orthopedic positioning or splinting for joint dislocations. For the rare infants who survive beyond the neonatal period, orthopedic procedures, physical therapy, and assistive devices may improve comfort and mobility. Long-term management would involve regular surveillance of respiratory status, skeletal integrity, and nutritional needs, with care coordinated among specialists familiar with complex skeletal disorders. Families are encouraged to engage in ongoing conversations with their healthcare team about goals of care and to seek psychosocial support services.

Atelosteogenesis type I is generally considered perinatally lethal, and many affected infants die shortly before or soon after birth because the small, underdeveloped thorax cannot support adequate breathing. Even so, clinical severity can differ, and isolated reports of longer survival illustrate that outcomes are not identical for every child. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialized skeletal dysplasia centers to understand recurrence risk, discuss supportive measures, and access emotional and community resources. Individual experiences differ significantly, and compassionate, individualized care planning remains central to optimizing quality of life.