SNP Shot: Genomic Insights

PMM2-congenital disorder of glycosylation (PMM2-CDG), also called congenital disorder of glycosylation type Ia, is a genetic condition impacting various systems in the body. The symptoms and their intensity differ significantly among those affected, even within the same family.

Typically, signs and symptoms of PMM2-CDG appear in infancy. Affected babies might exhibit poor muscle tone (hypotonia), inverted nipples, unusual fat distribution, misaligned eyes (strabismus), delayed development, and difficulty gaining weight and growing appropriately (failure to thrive). Many infants with PMM2-CDG also have an underdeveloped cerebellum, the part of the brain responsible for coordinating movement. Sometimes, individuals with this condition have distinctive facial features, such as a high forehead, triangular face, large ears, and thin upper lip. Elevated liver function tests, seizures, fluid accumulation around the heart (pericardial effusion), and blood clotting problems can also occur in children with PMM2-CDG. Sadly, about 20% of affected infants do not survive their first year due to multiple organ failure.

The most severe form of PMM2-CDG is characterized by hydrops fetalis, a buildup of excess fluid in the body before birth. Babies with hydrops fetalis are often stillborn or die shortly after birth.

Individuals with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk without assistance. They may also experience stroke-like episodes characterized by extreme fatigue (lethargy) and temporary paralysis. Recovery from these episodes generally takes weeks to months.

During adolescence or adulthood, individuals with PMM2-CDG can develop reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and stiff joints (contractures). Some may develop retinitis pigmentosa, an eye disorder leading to vision loss. Females with PMM2-CDG typically have hypergonadotropic hypogonadism, impacting hormone production essential for sexual development, preventing them from going through puberty. Affected males usually experience normal puberty but often have small testes.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that both copies of the PMM2 gene in each cell must have mutations for the condition to develop. The parents of a child with PMM2-CDG each carry one copy of the mutated gene but usually do not show any signs or symptoms of the condition themselves.