Jalili syndrome

Overview

Jalili syndrome is a rare inherited disorder that combines two major clinical features: cone-rod dystrophy and amelogenesis imperfecta. Cone-rod dystrophy affects the retina, leading to progressive vision loss, while amelogenesis imperfecta results in defective tooth enamel formation. First described in a consanguineous Arab family in 1988 by Dr. Ikram Jalili, the syndrome has since been reported in a limited number of families worldwide. It represents a syndromic form of inherited retinal dystrophy with dental anomalies.

Causes

Jalili syndrome is caused by mutations in the CNNM4 gene (cyclin and CBS domain divalent metal cation transport mediator 4), located on chromosome 2q11. This gene is believed to be involved in metal ion transport, which is essential for normal development and function of retinal photoreceptor cells and dental enamel-forming cells (ameloblasts). The syndrome is inherited in an autosomal recessive manner, meaning both copies of the gene must be mutated for the condition to manifest.

Symptoms

The hallmark features of Jalili syndrome affect the eyes and teeth. Common symptoms include:

• Ocular Symptoms (Cone-Rod Dystrophy):

  • Reduced visual acuity from early childhood

  • Photophobia (light sensitivity)

  • Color vision defects

  • Progressive loss of peripheral and night vision

  • Nystagmus (involuntary eye movements) in some cases

• Dental Symptoms (Amelogenesis Imperfecta):

  • Thin, discolored, or pitted enamel

  • Increased risk of tooth decay and sensitivity

  • Abnormal tooth shape or early tooth wear

Diagnosis

Diagnosis of Jalili syndrome involves a combination of ophthalmologic, dental, and genetic evaluations. Key diagnostic steps include:

• Detailed eye examination, including fundus imaging, visual field testing, and electroretinography (ERG) to assess retinal function

• Dental X-rays and clinical evaluation to identify enamel defects typical of amelogenesis imperfecta

• Genetic testing to confirm mutations in the CNNM4 gene

• Family history analysis to identify autosomal recessive inheritance patterns

Treatment

There is currently no cure for Jalili syndrome, but treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach involving ophthalmologists, dentists, and genetic counselors is essential. Treatment strategies may include:

• Low vision aids and assistive devices for visual impairment

• Sunglasses or photochromic lenses to reduce light sensitivity

• Regular dental care, including restorations, crowns, or sealants to protect affected teeth

• Fluoride treatments and oral hygiene education to minimize decay risk

• Genetic counseling for affected families and carrier detection

Prognosis

The long-term outlook for individuals with Jalili syndrome depends on the severity of the retinal and dental symptoms. Visual impairment tends to be progressive, with many individuals experiencing significant vision loss by early adulthood. However, the degree of visual loss can vary. Dental issues can usually be managed effectively with modern restorative dentistry. With appropriate care, individuals can maintain good oral health and adapt to vision challenges, enabling a reasonable quality of life.