craniolenticulosutural dysplasia

Craniolenticulosutural dysplasia, also known as Boyadjiev-Jabs syndrome or CLSD, is a condition affecting craniofacial development and the skeleton. It is characterized by features such as large, late-closing fontanels, hypertelorism, early-onset cataract, and a mild generalized skeletal dysplasia. The genetic basis of the condition involves pathogenic variants in the SEC23A gene, and it follows an autosomal recessive inheritance pattern. This condition is very rare, meaning it affects fewer than 1 in 1,000,000 people.

Individuals with craniolenticulosutural dysplasia typically present with a distinct pattern of craniofacial and skeletal features. Characteristic findings include a wide anterior fontanel, delayed closure of the anterior fontanel, hypertelorism, and posterior Y-sutural cataract. Other consistently observed features are prominent nasal bridge, sparse and coarse hair, frontal bossing, midface retrusion, and various dental abnormalities such as delayed eruption and carious teeth. Some individuals may also exhibit skeletal features such as a narrow chest, high iliac wing, and posterior wedging of vertebral bodies, while a subset may experience cryptorchidism and scoliosis. Not all individuals experience all features, and severity varies considerably.

Craniolenticulosutural dysplasia is caused by pathogenic variants in the SEC23A gene, which plays a crucial role in protein transport within cells. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received a mutated copy of the gene from each parent. This condition is more common when parents share a common ancestor, as the likelihood that both carry the same rare variant is increased. Genetic counseling can provide families with further insights regarding inheritance and planning for future pregnancies.

Currently, there are no FDA-approved treatments for craniolenticulosutural dysplasia, and management focuses on supportive care and symptom management. Care is highly individualized and typically involves a multidisciplinary team to address the diverse clinical features, with regular surveillance to monitor for potential complications. Although there are no foundational therapies specific to this condition, establishing a tailored care plan that may include ophthalmologic, orthopedic, and dental evaluations is important. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to support families in understanding the condition and planning for the future.

The course of craniolenticulosutural dysplasia can vary widely between individuals. With current standards of care, many people experience a relatively stable clinical course after initial presentation, although some may encounter challenges related to skeletal or ocular complications. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with the condition in order to receive personalized guidance and support.