Pontocerebellar hypoplasia (PCH) is a group of rare neurodegenerative disorders characterized by underdevelopment (hypoplasia) of the pons and cerebellum in the brain. These structures are essential for motor control, coordination, and other neurological functions.
Pontocerebellar hypoplasia genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Pontocerebellar hypoplasia is a genetically heterogeneous condition that can result from mutations in different genes. The severity of symptoms and the age of onset can vary depending on the specific genetic mutation involved.
Standard features of pontocerebellar hypoplasia may include:
- Severe developmental delay: Children with PCH typically experience delays in reaching developmental milestones, such as sitting, crawling, and walking.
- Problems with movement: Motor impairments, including muscle weakness, tremors, and difficulty with coordination, are common.
- Intellectual disability: Cognitive impairment is often present, ranging from mild to severe.
- Respiratory difficulties: Some individuals with PCH may have breathing problems, which can be life-threatening.
- Seizures: Seizures may occur in individuals with pontocerebellar hypoplasia.
- Feeding difficulties: Swallowing and feeding problems are common, leading to nutrition and weight gain challenges.
- Abnormal muscle tone: Hypotonia (low muscle tone) is frequently observed.
Diagnosing pontocerebellar hypoplasia is typically based on clinical features, neuroimaging studies (such as magnetic resonance imaging or MRI), and genetic testing to identify specific mutations.
There is no cure for pontocerebellar hypoplasia, and treatment focuses on supportive care to manage symptoms and improve the quality of life. This may include physical and occupational therapy, speech therapy, and medications to address specific symptoms.
One of the most affected genes in cerebellopontine hypoplasia is TSEN54. This gene encodes for a subunit of the transfer RNA splicing and splicing complex, which is involved in processing various types of RNA.
The c.919G>T (p.Ala307Ser) mutation in the TSEN54 gene is present in 90% of those with pontocerebellar hypoplasia type 2. This variant affects the structure of the protein. The mutation has been found in both homozygosis and compound heterozygosis.
Pontocerebellar hypoplasia genetic testing analyzes the 1 most frequent pathogenic mutation of the TSEN54 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
