coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness

Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness is a multi-system condition affecting the eyes, skeletal system, and other organ systems. It arises from pathogenic variants in the MITF gene and follows an autosomal recessive inheritance pattern, meaning that affected individuals inherit two copies of the gene alteration. The condition is exceptionally rare, affecting fewer than 1 in 1,000,000 people. Although it can be diagnosed in early childhood, the severity and extent of features vary considerably from person to person.

The clinical features of this condition are widespread and affect multiple systems. Ophthalmologic findings include microphthalmia, coloboma, iris transillumination defect, microcornea, and cataract, while craniofacial and skeletal features such as macrocephaly (always present), frontal bossing, clinodactyly of the 5th finger, preauricular pit, and short stature are frequently observed. In addition, patients may present with features such as osteopetrosis, increased bone mineral density, generalized hypopigmentation, decreased body weight, and congenital sensorineural hearing impairment. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the MITF gene. It follows an autosomal recessive pattern, which means that an affected individual inherits two copies of the altered gene, one from each parent. This condition is more common when parents share a common ancestor, as both are more likely to carry the same rare variant, leading to a 25% recurrence risk for each pregnancy. Genetic counseling is recommended to help families understand the implications and to explore options for future family planning.

Currently, management focuses on supportive care and symptom management as no specific foundational therapies or FDA-approved treatments are available for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the various systems affected. Regular surveillance is an essential part of long-term care, helping to identify potential complications early so that proactive measures can be taken. Genetic counseling is recommended to explore family planning options and to guide ongoing management decisions.

Outcomes vary depending on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals are able to manage symptoms and lead fulfilling lives, though the condition may present complex challenges across multiple systems. Severity and symptoms vary widely between individuals, and outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists or genetic counselors for ongoing guidance and support.