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Disease Profile

Pontocerebellar hypoplasia type 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q04.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pontocerebellar hypoplasia with infantile spinal muscular atrophy; Pontocerebellar hypoplasia with anterior horn cell disease

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Pontocerebellar hypoplasia type 1 (PCH1) is a genetic disease that affects the development of the brain. Babies and children with this disease 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, which is located at the base of the brain in an area called the brainstem, sends signals between the cerebellum and the rest of the brain.[1] Individuals with PCH1 also experience a degeneration of the anterior horn cells, which are responsible for helping the spinal cord send signals to the muscles. Problems with the anterior horn cells cause severe muscle weakness.[2][3]

PCH1 is caused by mutations to EXOSC3, TSEN54, RARS2, and VRK1.[4] The disease is inherited in an autosomal recessive manner.[1] Diagnosis of PCH1 is based on brain imaging and tests to rule out other causes of problems with brain development.[2] Treatment for PCH1 is aimed at relieving the symptoms of the disease. Most children with PCH1 pass away in infancy or early childhood.[1][2]

Symptoms

Pontocerebellar hypoplasia type 1 (PCH1) may first present in the prenatal period when mothers feel reduced movement of the baby (reduced fetal movement). The presence of too much fluid surrounding the baby in the womb (polyhydramnios) may also be noted. In most cases, signs and symptoms of PCH1 can be observed in the newborn period, as babies may not be able to breathe properly (respiratory insufficiency) and may have muscle weakness (hypotonia). Babies may also be born with the inability to move joints (joint contractures).[2]

Later in the newborn period, other symptoms may become apparent including visual impairment, uncontrolled movements of the eye (nystagmus), and uncontrolled movements of the muscles (ataxia). Babies with PCH1 may struggle to feed at the breast or with a bottle because their swallowing muscles are weakened. After a few months, the baby may have a smaller than typical head size (microcephaly).[4] Affected babies also typically do not meet milestones such as being able to sit up, and they may have intellectual disability.[1]

In some cases, babies affected by PCH1 may not show signs or symptoms of the disease until they are a few months old. In these cases, the baby may have a better long-term outlook than other affected individuals.[2] Individuals who survive past infancy may develop seizures as they get older.[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormal foot morphology
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity

[ more ]

0001760
Ataxia
0001251
Autosomal recessive inheritance
0000007
Basal ganglia gliosis
0006999
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Congenital contracture
0002803
Congenital onset
Symptoms present at birth
0003577
Degeneration of anterior horn cells
0002398
EMG: neuropathic changes
0003445
Fasciculations
Muscle twitch
0002380
Feeding difficulties in infancy
0008872
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hyperreflexia
Increased reflexes
0001347
Hypoplasia of the pons
0012110
Hypoplasia of the ventral pons
0006850
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Neuronal loss in basal ganglia
0200147
Progressive
Worsens with time
0003676
Psychomotor retardation
0025356
Respiratory insufficiency
Respiratory impairment
0002093
Spinal muscular atrophy
Spinal muscle degeneration
Spinal muscle wasting

[ more ]

0007269

Cause

About half of all cases of pontocerebellar hypoplasia type 1 (PCH1) are caused by mutations (changes) in the EXOSC3 gene. Other genes that have been associated with PCH1 include TSEN54, RARS2, and VRK1.[1] These genes are normally responsible for helping the body process RNA, which is a form of genetic information similar to DNA. When RNA cannot be processed properly, the body does not receive instructions about how it should work and develop. It is thought that the brain and muscles are particularly susceptible to changes in RNA processing. Therefore, when there are changes in any of the genes mentioned above, the body does not process RNA properly, causing the brain and muscles to not work properly.[1]

Diagnosis

Pontocerebellar hypoplasia type 1 (PCH1) is typically diagnosed when healthcare professionals see signs and symptoms consistent with the disease. Tests that may be ordered include an MRI or CT scan of the brain to visualize the cerebellum and the pons. Other tests such as metabolic tests may also be completed to rule out other causes of the symptoms.[2] If PCH1 is the suspected cause of the symptoms, genetic testing may be done to confirm the diagnosis.[5]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for pontocerebellar hypoplasia type 1 (PCH1) is aimed at treating the signs and symptoms present in each individual. Management options may include physical therapy or braces on the limbs to help with joint contractures, ventilation machines for breathing assistance, antiseizure medication, and a feeding tube if the child is not able to eat without one.[4] These treatment options are aimed at relieving some of the symptoms of PCH1, but there is no cure for the disease.[2][5]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Pontocerebellar hypoplasia type 1. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Pontocerebellar hypoplasia type 1. Click on the link to view a sample search on this topic.

          References

          1. Pontocerebellar hypoplasia. Genetics Home Reference (GHR). November 2014; https://ghr.nlm.nih.gov/condition/pontocerebellar-hypoplasia.
          2. Omar S and Ajibola A. Pontocerebellar Hypoplasia. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/pontocerebellar-hypoplasia/.
          3. Pontocerebellar Hypoplasia Type 1A; PCH1A. Online Mendelian Inheritance in Man. April 14, 2017; https://omim.org/entry/607596.
          4. Namavar Y, Barth PG, Poll-The BT, and Baas F. Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia. Orphanet J Rare Dis. 2011; 6(50):https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-6-50.
          5. Eggens VRC, Barth PG, and Baas F. EXOSC3-Related Pontocerebellar Hypoplasia. GeneReviews. August 21, 2014; https://www.ncbi.nlm.nih.gov/books/NBK236968/.
          6. Baas F. Pontocerebellar hypoplasia type 1. Orphanet. July 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2254.

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