cranioectodermal dysplasia 3

Cranioectodermal dysplasia 3 is a multisystem condition characterized by abnormalities in dental, skeletal, and renal development. It is caused by mutations in the IFT43 gene, a critical component involved in the function and development of cilia in various tissues. Affected individuals typically present in early childhood with features such as widely spaced teeth, short stature, and kidney-related issues. Given its rarity, precise prevalence estimates are not well established, and the condition is recognized as an uncommon genetic disorder.

The clinical presentation of cranioectodermal dysplasia 3 is marked by several characteristic features. Nearly all affected individuals have widely spaced teeth, nephronophthisis, rhizomelia, short stature, a narrow chest, broad and short nails, and brachydactyly. In addition, many experience variable features such as stage 5 chronic kidney disease, frontal bossing, sagittal craniosynostosis, cirrhosis, sandal gap deformity, micrognathia, toe syndactyly (either 2-4 or 2-3), postaxial polydactyly, telecanthus, sparse hair, macrocephaly, an everted lower lip vermilion, peripheral pulmonary artery stenosis, hypoplasia of the teeth, scaphocephaly, and, less commonly, dolichocephaly. Not all individuals experience every feature, and severity varies considerably.

Cranioectodermal dysplasia 3 is caused by mutations in the IFT43 gene, which plays a vital role in intraflagellar transport and the proper functioning of cilia in multiple organ systems. In this autosomal recessive condition, an affected individual inherits two copies of the pathogenic variant, one from each parent. This genetic pattern means that families with shared ancestry may have an increased risk, and genetic counseling can provide further insights for family planning and recurrence risk.

Currently, management focuses on supportive care and symptom management, as there are no specific foundational or targeted therapies approved for cranioectodermal dysplasia 3. Treatment is tailored to the individual and typically involves a multidisciplinary team, with regular surveillance being an essential part of long-term care to identify potential complications early. Regular monitoring, such as renal evaluations and assessments by skeletal specialists, is recommended to manage evolving symptoms. Patients should discuss treatment options with their healthcare team and seek genetic counseling to assist in family planning and to connect with specialists experienced in managing this condition.

The long‐term outlook for individuals with cranioectodermal dysplasia 3 varies considerably, with outcomes influenced by the severity of multisystem involvement and the timeliness of supportive interventions. Many individuals face chronic challenges related to kidney function, skeletal abnormalities, and dental issues; however, modern standards of care, including consistent surveillance and multidisciplinary management, can help improve quality of life. That severity and symptoms vary widely between individuals, and while some may experience a stable course, others might require more intensive management over time. Families often find it helpful to connect with specialists experienced in this condition, and ongoing genetic counseling is recommended as part of long-term care. Outcomes described in medical literature continue to evolve as standards of care improve.