cranioectodermal dysplasia 5

Cranioectodermal dysplasia 5 is a multisystem condition that affects the kidneys, skeletal system, eyes, and nervous system. It is caused by pathogenic variants in the IFT140 gene, which is important for cellular ciliary function. The condition is inherited in an autosomal recessive pattern, meaning that affected individuals inherit two altered copies of the gene. Precise prevalence estimates are not well established, and the condition is recognized by a consistent presence of its marked clinical features.

The clinical presentation of cranioectodermal dysplasia 5 is characterized by a constellation of findings that affect multiple organ systems. Renal involvement is prominent with features such as stage 3 and stage 4 chronic kidney disease, renal cysts, tubulointerstitial nephritis, reduced renal corticomedullary differentiation, and renal cortical hyperechogenicity; additionally, glycosuria is consistently observed. Skeletal and craniofacial manifestations include slender fingers, flattened and cone-shaped epiphyses, brachydactyly, broad ribs, a narrow chest, sagittal craniosynostosis, microretrognathia, a pointed chin, and protruding ears, while ophthalmologic findings include high hypermetropia and blindness. Neurologically, affected individuals experience typical absence seizures and absent speech. That not all individuals experience every feature, and severity varies considerably.

Cranioectodermal dysplasia 5 is caused by pathogenic variants in the IFT140 gene, which plays a crucial role in the function of cilia—cellular structures essential for proper organ development and homeostasis. The condition follows an autosomal recessive inheritance pattern, meaning that an individual must inherit two copies of the altered gene, one from each parent, to be affected. This genetic mechanism underscores the importance of genetic counseling for families to understand recurrence risks and implications for family planning.

Currently, management of cranioectodermal dysplasia 5 focuses on supportive care and symptom management tailored to the specific needs of the individual. Due to the multisystem involvement, a multidisciplinary care approach is essential, and regular surveillance is an integral part of long-term management to detect emerging complications early. While there are no specific foundational or targeted therapies available at this time, clinical management may involve addressing kidney function, monitoring skeletal development, and providing supportive interventions for neurological challenges. Patients should discuss treatment options with their healthcare team and consider genetic counseling to explore family planning and further management strategies.

The course of cranioectodermal dysplasia 5 is variable, with outcomes differing significantly based on the severity of organ involvement and access to specialized care. With current standards of care, many individuals benefit from ongoing monitoring and supportive interventions, although the condition remains a lifelong challenge. Outcomes described in medical literature continue to evolve as standards of care improve, and patients may experience periods of stability interspersed with challenges related to renal, skeletal, and neurological functions. Genetic counseling, along with connecting with specialists experienced in managing multisystem conditions, is recommended to help guide families through the complex care pathway.