SNP Shot: Genomic Insights

Pontocerebellar hypoplasia (PCH) encompasses a group of related disorders affecting brain development. The term highlights the pons and cerebellum, brain structures often severely impacted. The pons, located in the brainstem, relays signals between the cerebellum and other brain regions. The cerebellum, at the back of the brain, is crucial for coordinating movement. "Hypoplasia" signifies the underdevelopment of these areas.

PCH can also hinder the growth of other brain regions, resulting in microcephaly, an unusually small head size. While often not present at birth, microcephaly becomes noticeable as brain growth slows during infancy and early childhood.

Researchers have identified at least ten types of PCH. All are characterized by impaired brain development, developmental delays, movement problems, and intellectual disability. Brain abnormalities are typically present at birth, sometimes even detected prenatally. While many children with PCH survive only into infancy or childhood, some have lived into adulthood.

The two primary forms of PCH are type 1 (PCH1) and type 2 (PCH2). PCH1, in addition to the brain abnormalities, causes muscle movement problems due to motor neuron loss in the spinal cord, similar to spinal muscular atrophy. Individuals with PCH1 also experience severe hypotonia (weak muscle tone), joint contractures, vision impairment, and early-onset breathing and feeding difficulties.

PCH2 commonly involves a lack of voluntary motor skills (like grasping, sitting, or walking), dysphagia (swallowing problems), and absent communication, including speech. Affected children often develop temporary jitteriness (generalized clonus) early in infancy, along with abnormal movements like chorea or dystonia, and spasticity (stiffness). Impaired vision and seizures are also frequent.

PCH types 3 through 10 appear rare, reported in only a small number of individuals. Due to overlapping features and shared gene mutations, researchers suggest viewing the types as a spectrum rather than distinct conditions.

Inheritance:

PCH is inherited in an autosomal recessive pattern. This means both copies of the responsible gene in each cell must have mutations for the condition to manifest. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically show no signs or symptoms themselves.