Lateral meningocele syndrome

Did You Know?

• The syndrome was first described by Lehman et al. in 1977 in a 14-year-old girl whose mother shared some findings.
• There have been 16 reported cases in 14 different families, with 9 male and 7 female patients.
• De novo mutations of the NOTCH3 gene are more common than inherited cases.

Signs and symptoms

Facial features include dolichocephaly, hypertelorism, ptosis, microretrognathia, high arched palate, long flat philtrum, and low set ears. Non-facial features comprise hyperextensibility, hypotonia, lateral meningoceles, bladder dysfunction, and neuropathy. Motor skill development is delayed in infancy, but intelligence usually remains unaffected. Additional features are low muscle tone, decreased muscle bulk, loose joints, and hernias.

Diagnosis

Diagnosis may be suspected based on distinctive facial features, lateral meningoceles, hyperextensibility, and hypotonia. Radiographic imaging of the spine can clinically identify lateral meningoceles. Molecular genetic testing confirms the diagnosis through a pathogenic variant in NOTCH3. Historically, maldevelopment of the spinal cord, cerebellum, and cerebral cortex helped distinguish the disorder; all historical cases were diagnosed before age 20, with some as early as age 5.

Treatment

No specific treatment exists for Lehman syndrome; only symptom management is recommended. Pain management options are available for chronic pain. Rarely, surgical intervention is needed for neurologic manifestations. Some patients benefit from rehabilitation medicine, physiotherapy, and routine management of cleft palate, hearing loss, congenital cardiac defects, genitourinary abnormalities, and feeding difficulties.

Genetics

The syndrome appears inherited in an autosomal dominant pattern, though X-linked inheritance has not been completely ruled out; males and females are affected equally. The mutation truncates the protein, causing loss of the PEST sequence, which prolongs the protein's half-life and increases signaling effects. NOTCH3 produces the Notch 3 receptor protein; ligands bind to it to control gene activity in the nucleus. The truncation removes the Notch 3 intracellular domain (NICD), which normally disintegrates after completing its nuclear function, leading to prolonged presence in the nucleus and continued gene activity.