muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 is a severe neuromuscular disorder that affects multiple organ systems, most the brain, eyes, and muscles. Caused by mutations in the POMT1 gene, which encodes the enzyme O-mannosyltransferase 1, the condition is inherited in an autosomal recessive manner. It typically presents in infancy with profound developmental delays, muscle weakness, and distinctive brain and ocular malformations. Because precise prevalence data is not available, the condition is understood to be very uncommon.

The clinical presentation of this condition is dominated by severe neurological and muscular features. Infants exhibit neonatal hypotonia and feeding difficulties, and almost all affected individuals experience global developmental delay, absent speech, and profound cognitive impairment. Characteristic brain malformations such as cerebellar hypoplasia, Dandy-Walker malformation, agyria, and type II lissencephaly are always present, along with ocular anomalies like retinal dysplasia, microphthalmia, and corneal opacity. Additional consistent findings include elevated circulating creatine kinase levels, seizures, and other craniofacial anomalies such as mask-like facies. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the POMT1 gene, which is responsible for producing the enzyme O-mannosyltransferase 1. Defective function of this enzyme disrupts the proper glycosylation of proteins, contributing to the development of both muscular and neurological abnormalities. Inheritance is autosomal recessive, meaning that affected individuals inherit one altered copy of the gene from each carrier parent. Families are advised that the recurrence risk in future pregnancies is approximately 25% if both parents are carriers, and genetic counseling can be a valuable resource in planning and assessing risk.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. A multidisciplinary approach is essential, with care provided by various specialists who address neurological, ophthalmologic, and orthopedic needs. Regular surveillance is an important component of long-term care, helping to detect complications early and guide timely interventions. Patients and families are encouraged to discuss treatment options and tailored care plans with their healthcare team, and genetic counseling is recommended to help with family planning and understanding the condition.

The prognosis for this condition is highly variable and challenging, with many affected individuals experiencing a shortened lifespan and severe developmental impairment. Outcomes depend on the severity of symptoms, age at diagnosis, and access to specialized supportive care. With current standards of care, the course of the disorder may include early onset of severe symptoms followed by a period of relative stabilization, although many cases are associated with early death. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with genetic counselors and specialists who understand this complex condition.

A clinical trial is currently underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.