National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Pontocerebellar hypoplasia type 4


Other Names:
Encephalopathy fatal infantile with olivopontocerebellar hypoplasia
Categories:
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 166063

Definition
Pontocerebellar hypoplasia type 4 (PCH4) is a very rare form of PCH (see this term), characterized by prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death.

Epidemiology
PCH4 has been reported in 10 families to date.

Clinical description
PCH4 is characterized prenatally by polyhydramnios. Neonates present with microcephaly, central apnea requiring respiratory support, dysmorphism (sloping forehead, midface hypoplasia, micrognathia), contractures (50%) ''arthrogryposis'', severe clonus,and hypertonia. PCH4 affected babies usually do not live beyond the neonatal period. Weaning from mechanical ventilation is difficult and usually fails.

Etiology
PCH4 is caused by a compound heterozygosity for p.A307S plus non-sense or splice site mutations in the TSEN54 gene. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5 (see this term). PCH4 is inherited in an autosomal recessive manner.

Diagnostic methods
MRI (usually performed at autopsy) demonstrates microcephaly due to delayed neocortical maturation with underdeveloped cerebral hemispheres, increased volume of extracerebral cerebrospinal fluid, wide midline cava, pontocerebellar hypoplasia with large denuded areas without folia of the cerebellar hemispheric cortex and a severely affected vermis.

Visit the Orphanet disease page for more resources.
Last updated: 7/1/2013

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.

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Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Arthrogryposis multiplex congenita 0002804
Central apnea 0002871
Congenital microcephaly 0011451
Hypertonia 0001276
Hypoplasia of the brainstem
Small brainstem
Underdeveloped brainstem
[ more ] 		0002365
Myoclonus 0001336
Olivopontocerebellar hypoplasia 0006955
Polyhydramnios
High levels of amniotic fluid
0001561
Respiratory failure requiring assisted ventilation 0004887
Seizure 0001250
5%-29% of people have these symptoms
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Sloping forehead
Inclined forehead
Receding forehead
[ more ] 		0000340
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Autosomal recessive inheritance 0000007
Congenital contracture 0002803
Congenital onset
Symptoms present at birth
0003577
Death in infancy
Infantile death
Lethal in infancy
[ more ] 		0001522
Gliosis 0002171
Hypoplasia of the pons 0012110
Infantile encephalopathy 0007105
Loss of Purkinje cells in the cerebellar vermis 0007001
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Respiratory failure 0002878
Severe global developmental delay 0011344
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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

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

  • 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

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • 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 4. Click on the link to view a sample search on this topic.

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