What are the other Names for this Condition? (Also known as/Synonyms)

• PCH (Pontocerebellar Hypoplasia)

What is Pontocerebellar Hypoplasia? (Definition/Background Information)

• Pontocerebellar Hypoplasia (PCH) is a group of conditions affecting the brain, characterized by underdevelopment of the cerebellum and pons
• The cerebellum normally coordinates movement and the pons (located in the brainstem) transmits signals from the cerebellum to the rest of the brain
• Several forms of PCH have been described, each having some different signs and symptoms but all characterized by problems with movement, delayed psychomotor development, and intellectual disability
• Although each form has a different genetic cause, they are all inherited in an autosomal recessive manner. Many children with PCH live only into infancy or childhood, although some individuals have lived into adulthood. Treatment is symptomatic and supportive

(Source: Pontocerebellar Hypoplasia; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Pontocerebellar Hypoplasia? (Age and Sex Distribution)

• Pontocerebellar Hypoplasia is a rare inherited condition. The exact prevalence of this disorder is not known
• The onset of symptoms may be apparent at birth, or in infancy
• The condition is known to occur in both genders
• Worldwide, individuals belonging to all races and ethnicities may be affected

What are the Risk Factors for Pontocerebellar Hypoplasia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Pontocerebellar Hypoplasia can be inherited
• Currently, no other risk factors have been clearly identified for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pontocerebellar Hypoplasia? (Etiology)

• The different subtypes of Pontocerebellar Hypoplasia (PCH) are caused by mutation(s) in several genes:
  • PCH1A, caused by VRK1 gene mutation(s)
  • PCH1B, caused by EXOSC3 gene mutation(s), accounts for approximately 50% of PCH1 cases
  • PCH2, occurs due to mutation(s) in TSEN54, TSEN2, TSEN34, and SEPSECS genes
  • PCH3, causative gene not identified
  • PCH4, occurs due to mutations in the TSEN54 gene
  • PCH5, causative gene not identified
  • PCH6, caused by mutations in the RARS2 gene
  • PCH7, causative gene not identified
  • PCH8 is caused by mutations in the CHMP1A gene
• All subtypes are inherited in an autosomal recessive manner. The PCH1 and PCH2 subtypes are the most common forms of Pontocerebellar Hypoplasia
• In some cases, causes other than inherited gene mutations (such as an infection or exposure to toxins) have been suspected or reported

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Pontocerebellar Hypoplasia?

The signs and symptoms of Pontocerebellar Hypoplasia may include:

• Microcephaly
• Feeding problems
• Hypotonia
• Joint contractures
• Problems with movement
• Involuntary muscle twitches
• Delayed psychomotor development
• Impaired vision
• Intellectual disability
• Seizures

How is Pontocerebellar Hypoplasia Diagnosed?

Pontocerebellar Hypoplasia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Differential diagnosis to rule out other conditions that may present with similar signs and symptoms
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pontocerebellar Hypoplasia?

The complications of Pontocerebellar Hypoplasia may include:

• Problems with swallowing, which may lead to malnutrition
• Inability to grasp objects
• Inability to sit or walk independently
• Impaired speech development
• Sleep apnea
• Rhabdomyolysis (breakdown of skeletal muscles), which may lead to kidney dysfunction
• Malignant hypothermia, which may cause rigidity of muscles
• Risk of falls and injury due to seizures
• Severe respiratory distress

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Pontocerebellar Hypoplasia Treated?

There is no cure for Pontocerebellar Hypoplasia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. Some treatment methods may include:

• Feeding tube to aid in maintenance of proper nutrition
• Medication for seizures
• Medication to control involuntary muscle movements
• Respiratory support for severe breathing problems

How can Pontocerebellar Hypoplasia be Prevented?

Pontocerebellar Hypoplasia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Pontocerebellar Hypoplasia? (Outcomes/Resolutions)

• The prognosis of Pontocerebellar Hypoplasia is poor, and many affected individuals succumb to the condition in infancy or childhood
• Complications from the condition may lead to respiratory failure and sudden infant death syndrome 
• A few individuals have been reported to live into adulthood
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Pontocerebellar Hypoplasia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/