colobomatous microphthalmia-rhizomelic dysplasia syndrome

Colobomatous microphthalmia-rhizomelic dysplasia syndrome is a very rare developmental disorder that primarily affects the eyes and limbs, leading to a variety of ocular anomalies and skeletal abnormalities. It results from pathogenic variants in the MAB21L2 gene, which plays an important role during early embryonic development. Both autosomal recessive and autosomal dominant inheritance patterns have been reported, indicating that the condition may be passed down in different ways. Because it is very rare, affecting fewer than 1 in 1,000,000 people, clinical recognition and diagnosis are challenging and require a high index of suspicion.

The clinical presentation includes a spectrum of ocular abnormalities such as microphthalmia, coloboma, anophthalmia, microcornea, and other defects like corectopia and cataract. In addition, individuals often exhibit symmetric limb rhizomelia which is associated with short stature and contractures of large joints. Many affected individuals may also experience moderate intellectual disability with autistic features, macrocephaly, dysmorphic features, and urogenital anomalies such as hypospadias and cryptorchidism. Other reported features include strabismus, recurrent patellar dislocation, toe and finger syndactyly, precocious puberty, sclerocornea, epicanthus, pes planus, and a long philtrum. Not all individuals experience all features, and severity varies considerably.

Colobomatous microphthalmia-rhizomelic dysplasia syndrome is caused by pathogenic variants in the MAB21L2 gene. This gene is essential for normal embryonic development, especially in the formation of the eyes and limbs. Multiple inheritance patterns have been reported, with both autosomal recessive and autosomal dominant modes of transmission. In autosomal recessive cases, the condition can be more common when parents share a common ancestor, meaning that both parents are more likely to carry the same rare variant. Genetic counseling is recommended to understand the implications for family members and future pregnancies.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved or specific foundational therapies for this condition. Treatment is highly individualized and typically involves a multidisciplinary team to address the various needs of affected individuals, including ophthalmologic, orthopedic, and developmental specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Patients should discuss treatment options with their healthcare team and consider genetic counseling to better understand the condition and implications for family planning.

The long-term outlook for colobomatous microphthalmia-rhizomelic dysplasia syndrome varies widely depending on the severity of the symptoms and the organs involved. With current standards of care and ongoing improvements in multidisciplinary management, many individuals experience a stable course and improved quality of life over time. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists experienced with this condition. Genetic counseling and support from expert centers can provide guidance tailored to each individual’s situation.