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Disease Profile

Pontocerebellar hypoplasia type 3

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)

Cerebellar atrophy with progressive microcephaly; CLAM; PCH with optic atrophy

Categories

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 97249

Definition
Pontocerebellar hypoplasia type 3 (PCH3), also known as cerebellar atrophy with progressive microcephaly (CLAM) is a rare form of pontocerebellar hypoplasia (see this term) with autosomal recessive transmission characterized neonatally by hypotonia and impaired swallowing and from infancy onward by seizures, optic atrophy and short stature, but none of the clinical findings are specific for PCH3.

Epidemiology
To date, PCH3 is reported in only 3 families.

Clinical description
Neonatally, PCH3 is characterized by hypotonia and impaired swallowing. From infancy onwards, the main features of PCH3 include progressive microcephaly with brachycephaly, optic atrophy, seizures during the first year of life, severe developmental delay, truncal hypotonia, with increased limb deep tendon reflexes and signs of spasticity of the limbs. Other characteristics such as facial dysmorphism (low set ears and prominent eyes), short stature and low weight are also reported. None of the clinical findings are specific.

Etiology
The etiology of PCH3 remains largely elusive. In 2 families, an implication of locus 7q11-21 has been demonstrated. PCH3 is inherited in an autosomal recessive manner.

Diagnostic methods
MRI demonstrates neocortical and pontocerebellar hypoplasia with pons and cerebellum equally affected a small brainstem, prominent sulci and lateral ventricles and decreased cerebral white matter volume. It is recommended to limit the diagnosis of PCH3 to families with PCH and linkage to 7q11-21, until more precise identification of the associated gene becomes possible.

Prognosis
There is no information on life expectancy, but reported PCH3 patients do not appear to regress.

Visit the Orphanet disease page for more resources.

Symptoms

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
Autosomal recessive inheritance
0000007
Brachycephaly
Short and broad skull
0000248
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Cerebral atrophy
Degeneration of cerebrum
0002059
Congenital onset
Symptoms present at birth
0003577
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

0004325
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hyperreflexia
Increased reflexes
0001347
Hypoplasia of the brainstem
Small brainstem
Underdeveloped brainstem

[ more ]

0002365
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypoplasia of the pons
0012110
Long palpebral fissure
Broad opening between the eyelids
Long opening between the eyelids
Wide opening between the eyelids

[ more ]

0000637
Long philtrum
0000343
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Macrotia
Large ears
0000400
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Optic atrophy
0000648
Poor head control
0002421
Progressive
Worsens with time
0003676
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257

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

    • 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 3. Click on the link to view a sample search on this topic.