Pontocerebellar hypoplasia is a group of related conditions that affect the development of the brain.
Researchers have described six forms of pontocerebellar hypoplasia. These forms have somewhat different signs and symptoms and different genetic causes. All forms of this condition are characterized by abnormal brain development, problems with movement, delayed development, and intellectual disability. The signs and symptoms are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.
People with these conditions have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. A region of the brain called the pons also fails to develop properly. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals from the cerebellum to the rest of the brain.
The various forms of pontocerebellar hypoplasia are caused by mutations in several different genes.VRK1 gene mutations have caused PCH1 in at least one family. Mutations in three related genes,TSEN2, TSEN34, and TSEN54, can result in PCH2. TSEN54 gene mutations are also responsible for PCH4. Mutations in the RARS2 gene can cause PCH6. The genetic causes of PCH3 and PCH5 are unknown.
The genes that have been found to cause pontocerebellar hypoplasia appear to play essential roles in the development and survival of nerve cells (neurons). Many of these genes are known or suspected to be involved in processing RNA molecules, which are chemical cousins of DNA. Fully processed, mature RNA molecules are essential for the normal functions of all cells, including neurons. However, it is unclear how mutations in genes related to RNA processing disrupt the normal development of the cerebellum and pons.
Researchers are working to find additional genetic changes that cause the different forms of pontocerebellar hypoplasia.
All of the recognized forms of pontocerebellar hypoplasia are inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Neonatal MRI of the brain reveals cerebellar and vermian hypoplasia but normal brain volume while follow-up studies portray evidence of progressive atrophy of the cerebellum, pons, cerebral cortex, and white matter. Activities of mitochondrial complexes I, III, and IV in muscle from this patient were markedly reduced, but activity of complex II was relatively preserved.
Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by impaired development of various parts of the brain (cerebellum, brainstem).
Where known, these disorders are inherited in an autosomal recessive fashion. As with the majority of genetic disorders, there is no known cure to PCH.