Elsahy-Waters syndrome

Elsahy-Waters syndrome is an extremely rare multisystem congenital anomaly syndrome characterized by distinctive facial, dental, skeletal, and genitourinary abnormalities. It is associated with mild intellectual disability and developmental delays, fitting into the broader category of dysmorphic syndromes. The condition is linked to variants in the CDH11 gene and has been described in only a few affected boys, indicating a possible male predominance. Given its rarity, it affects fewer than 1 in 1,000,000 individuals.

Individuals with Elsahy-Waters syndrome typically present with a constellation of physical and neurodevelopmental features. Characteristic findings include a broad nasal bridge, bulbous and wide nose, hypertelorism, and a pointed chin, alongside orofacial anomalies such as bifid uvula or partial cleft palate, high palate, and delayed eruption of teeth. Musculoskeletal findings such as fused cervical spinous processes, shortening of the phalanges, and pectus excavatum are also observed. Genitourinary anomalies such as hypospadias, bifid scrotum, and bilateral cryptorchidism are consistently reported. In addition, cognitive and developmental aspects manifest as mild intellectual disability and delayed fine motor development. Not all individuals experience all features, and severity varies considerably.

Elsahy-Waters syndrome is associated with variants in the CDH11 gene, which plays a role in cell adhesion and developmental processes. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received two copies of the altered gene, one from each parent. This inheritance pattern also means that the condition is more common when parents share a common ancestor, as they are more likely to both carry the same rare genetic variant. Families with an affected child have a recurrence risk of 25% for each subsequent pregnancy, which underscores the importance of genetic counseling.

Currently, management focuses on supportive care and symptom relief, as there are no FDA-approved or foundational therapies specific to Elsahy-Waters syndrome. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the various affected systems. Regular surveillance is an essential part of long-term care, helping to identify potential complications early, and supportive therapies may include interventions for developmental delays, dental care, and surgical correction of genitourinary or skeletal anomalies as needed. Genetic counseling is also recommended to help families understand inheritance and options for future family planning. Patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate for their situation.

The prognosis for Elsahy-Waters syndrome is variable, with outcomes depending on the severity of the congenital anomalies and the timely access to multidisciplinary care. With current standards of care, many individuals benefit from supportive therapies that improve quality of life, though challenges such as developmental delays and physical anomalies persist. Outcomes described in medical literature continue to evolve as standards of care improve, and the variability in symptoms means that not all individuals experience the same challenges. Families are encouraged to connect with genetic counselors and specialists to receive guidance on management and support, as well as to help plan for the future.

Clinical trials are currently underway exploring new treatment approaches for Elsahy-Waters syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.