endocrine-cerebro-osteodysplasia syndrome

Endocrine-cerebro-osteodysplasia syndrome is a severe, ultra-rare condition that affects the endocrine, cerebral, and skeletal systems. It is associated with pathogenic variants in the CILK1 gene. Affected individuals are neonates, and the condition is often fatal in the newborn period. The condition is very rare, affecting fewer than one in a million people. Ongoing research and a multidisciplinary care approach remain essential as our understanding of the disease evolves.

The clinical presentation is marked by a consistent set of characteristic features. All affected individuals exhibit deeply set eyes, postaxial polydactyly, hypotelorism, midface retrusion, ankyloblepharon, micrognathia, bowed forearm bones, brachydactyly, a sandal gap, ulnar deviation of the hand, micromelia, syndactyly, and a single transverse palmar crease. In addition, many present with a median cleft palate, while some experience a median cleft upper lip, hydrocephalus, microphallus, absent septum pellucidum, adrenal hypoplasia, bilateral cleft lip, low-set ears, laryngeal hypoplasia, fibular bowing, ventriculomegaly, or a thick upper lip vermilion. Not all individuals experience every feature, and severity varies considerably.

Endocrine-cerebro-osteodysplasia syndrome is caused by pathogenic variants in the CILK1 gene and follows an autosomal recessive inheritance pattern. This means that an affected individual inherits two copies of the altered gene, one from each parent. The condition is more common when parents share a common ancestor, as both are more likely to carry the same rare genetic variant. Genetic counseling is recommended for families to discuss carrier testing and to better understand recurrence risks.

Currently, management focuses on supportive care and symptom management since neither foundational nor FDA-approved treatments are available for endocrine-cerebro-osteodysplasia syndrome. A multidisciplinary approach is essential, with regular surveillance for potential complications affecting the endocrine, cerebral, and skeletal systems. Patients should discuss treatment options with their healthcare team to determine the most appropriate management plan, and genetic counseling is recommended for affected families.

The outlook for endocrine-cerebro-osteodysplasia syndrome is generally poor because the condition is associated with neonatal mortality. However, outcomes can vary depending on the severity of anomalies and the level of supportive care provided. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists familiar with this condition for ongoing guidance and support.

Clinical trials are underway exploring new treatment approaches for endocrine-cerebro-osteodysplasia syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility. Active research continues to shed light on this ultra-rare condition.