Craniosynostosis–anal anomalies–porokeratosis syndrome

Overview

Cranio-lenticulo-sutural dysplasia (CLSD) is a very rare genetic disorder that affects bone development, particularly in the skull, as well as the eyes and connective tissue. It is characterized by delayed closure of the cranial sutures and fontanelles, abnormal skull shape, Y-shaped cataracts in the eye lens, and other skeletal abnormalities. CLSD is part of the broader group of disorders known as skeletal dysplasias. Only a few cases have been reported in medical literature, making its full clinical spectrum not yet fully understood.

Causes

CLSD is caused by mutations in the SEC23A gene. This gene encodes a protein that is part of the COPII complex, which is essential for transporting proteins from the endoplasmic reticulum to the Golgi apparatus inside cells. Disruptions in this transport process can affect the development of bone and connective tissues. The disorder is inherited in an autosomal recessive pattern, meaning both copies of the SEC23A gene (one from each parent) must be mutated for a child to be affected.

Symptoms

The signs and symptoms of cranio-lenticulo-sutural dysplasia typically become noticeable in infancy or early childhood. Common clinical features include:

• Delayed closure of fontanelles and cranial sutures: Leading to an enlarged, soft skull

• Abnormal skull shape: Such as frontal bossing or wide-spaced sutures

• Y-sutural cataracts: Star- or Y-shaped opacities in the eye lens, which can affect vision

• Mild facial dysmorphism: Including a flat nasal bridge or wide-set eyes

• Skeletal anomalies: Including mild joint hypermobility or other minor bone abnormalities

• Normal or near-normal intelligence: Cognitive development is generally not affected

Diagnosis

Diagnosis of CLSD is based on clinical findings, imaging, ophthalmologic evaluation, and genetic testing. Diagnostic steps include:

• Physical and neurological exam: Assessment of skull growth, suture closure, and physical features

• Skull X-rays or CT scans: To visualize delayed suture closure and assess cranial shape

• Ophthalmologic examination: To detect Y-sutural cataracts

• Genetic testing: Sequencing of the SEC23A gene to confirm the diagnosis

• Family history: May help identify autosomal recessive inheritance patterns

Treatment

There is no cure for cranio-lenticulo-sutural dysplasia, so treatment focuses on managing symptoms and supporting development. Management strategies may include:

• Ophthalmologic surgery: Cataract removal to improve or preserve vision

• Cranial monitoring: Regular follow-up with neurosurgery or craniofacial specialists to assess skull growth and pressure

• Physical therapy: To improve mobility if joint laxity or skeletal issues are present

• Genetic counseling: For affected families to understand recurrence risks and inheritance

• Educational support: Although cognitive development is typically normal, early developmental assessments may still be recommended

Prognosis

The prognosis for individuals with CLSD is generally good, particularly with early recognition and management of complications such as cataracts. Most children with CLSD have normal intelligence and life expectancy. Surgical or therapeutic interventions can address many of the physical manifestations, and regular monitoring ensures that any emerging issues are managed effectively. As more cases are documented, long-term outcomes will become better understood.