axial spondylometaphyseal dysplasia

Axial spondylometaphyseal dysplasia is a very rare genetic condition that affects bone growth in the spine, chest, pelvis, and the upper portions of the arms and legs, and is also linked to progressive vision loss. Pathogenic changes in the CFAP410 gene have been found in affected individuals, and the disorder follows an autosomal recessive pattern, meaning a child must inherit two altered copies of the gene to develop the condition. Features usually become apparent in early childhood when short stature or an unusual chest or spine shape is noted, while vision problems often emerge later. Because it affects fewer than 1 in 1 million people worldwide, many clinicians may never encounter a case, making expert evaluation important. Severity and specific symptoms vary widely from person to person.

Axial spondylometaphyseal dysplasia primarily involves the skeleton. Children often have rhizomelia, meaning the upper arms and thighs are disproportionately short, and many develop a short trunk with scoliosis or a narrowed, barrel-shaped chest. These skeletal changes can restrict lung expansion, leading to a mild restrictive ventilatory pattern or recurring respiratory infections in some individuals. Vision is the second major system involved. All reported individuals eventually develop optic atrophy, a degeneration of the optic nerve that transmits visual information to the brain. Most also experience cone-rod or rod-cone retinal dystrophy, producing night blindness, reduced color vision, and gradual loss of acuity. Nystagmus, involuntary eye movements, is less common but may appear in childhood. Additional manifestations can affect other organs. Post-pubertal males have been reported with markedly reduced sperm motility, suggesting fertility issues. A minority of people develop splenomegaly or repeated episodes of pneumonia. Not all individuals experience all features, and the timing and severity of complications differ considerably.

The condition is caused by alterations in the CFAP410 gene. This gene provides instructions for a protein involved in the structure and function of cells that form bone and the light-sensing tissues of the eye. When both copies of CFAP410 are altered, bone growth at the spine and metaphyses becomes disordered and retinal cells gradually degenerate, explaining the combined skeletal and visual findings. Axial spondylometaphyseal dysplasia is inherited in an autosomal recessive manner. Each parent of an affected child typically carries one altered copy of CFAP410 but is healthy. When both parents are carriers, each pregnancy carries a 25 percent chance of having an affected child, a 50 percent chance of having a carrier child, and a 25 percent chance of having an unaffected, non-carrier child. Because the condition is so rare, it is more likely to occur when parents share a common ancestor, as this increases the chance that both carry the same rare genetic variant. Genetic counseling can help families understand carrier testing options and discuss reproductive choices.

Currently, management focuses on supportive care tailored to the individual rather than on disease-specific medications. Orthopedic follow-up addresses scoliosis progression and chest wall flexibility; physical and occupational therapy promote mobility and comfort. Regular ophthalmologic monitoring tracks vision changes, and low-vision services provide practical adaptations at school and home. Pulmonology input can help manage restrictive lung disease or recurrent pneumonia, and respiratory therapy may improve breathing efficiency. In males, assessment by reproductive specialists may be considered for family planning. Because the condition affects the skeleton, eyes, respiratory system, and in some cases the spleen and reproductive organs, long-term management requires a multidisciplinary team coordinated by a primary specialist familiar with skeletal dysplasias. Regular surveillance is recommended to detect spinal curvature progression, declining lung function, and worsening retinal disease so that interventions and assistive technologies can be introduced promptly. Families are encouraged to discuss individualized monitoring schedules with their care team and to seek genetic counseling for ongoing support.

Available reports suggest that short stature and skeletal differences are lifelong, while vision usually declines over childhood or adolescence and may lead to legal blindness in adulthood. Respiratory complications are variable; some individuals have only mild limitations, whereas others experience recurrent infections that can affect overall health. Fertility concerns in males relate to sperm motility, but data remain limited. Overall, outcomes depend on the severity of skeletal deformities, the rate of visual decline, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors to stay informed about emerging management strategies and to plan for education, mobility, and vision support across the lifespan.