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Disease Profile

Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome

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.

Unknown

Age of onset

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ICD-10

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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)

MPPH syndrome; Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus; Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

MPPH syndrome is a disorder characterized by the presence of multiple birth defects and developmental delay. Classic signs and symptoms include polymicrogyria, megalencephaly, seizures, polydactyly, and hydrocephalus. Other features might include characteristic facial features, low muscle tone (hypotonia), and impaired vision.[1] Mutations in at least three different genes have been identified that cause MPPH including PIK3R2, AKT3, and CCND2. Most cases of MPPH syndrome are new (de novo) in families with no prior history.[2][3] The diagnosis of MPPH syndrome is based on physical examination, imaging studies, and genetic testing.[1] Treatment is based on the signs and symptoms present in each person.

Symptoms

Common signs and symptoms of MPPH syndrome include polymicrogyria, megalencephaly, intellectual disability, seizures, polydactyly, and hydrocephalus. Additional signs and symptoms reported in the medical literature include thin corpus callosum, psychomotor impairment (i.e., slowing down of physical reactions, movements, and speech), impaired vision, low muscle tone (hypotonia), connective tissue symptoms including skin elasticity, mild characteristic facial differences, macrosomia (often at birth), and infantile spasms.[4][5][1]

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
80%-99% of people have these symptoms
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Megalencephaly
0001355
Polymicrogyria
More grooves in brain
0002126
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

0001162
30%-79% of people have these symptoms
Abnormal localization of kidney
Abnormal localisation of kidneys
0100542
Abnormal nasal morphology
Abnormal of nasal shape
Abnormal of shape of nose

[ more ]

0005105
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
High forehead
0000348
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Mitral regurgitation
0001653
Narrow mouth
Small mouth
0000160
Seizure
0001250
Telecanthus
Corners of eye widely separated
0000506
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629

Cause

Mutations in at least three different genes causes MPPH syndrome, including PIK3R2, AKT3, and CCND2. It is not known exactly how mutations within these genes causes MPPH syndrome; however, studies show that they are involved in a number of different functions in the body including vascular, limb, and brain development as well as regulation of growth.[2][3]

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

    Organizations Providing General Support

      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

      • MedlinePlus Genetics contains information on Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome in a table called Phenotypic Series. Each entry in OMIM includes 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 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome. Click on the link to view a sample search on this topic.

          References

          1. Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Mirzaa GM, Conway RL, Gripp KW, Lerman-Sagie T, Siegel DH, deVries LS, Lev D, Kramer N, Hopkins E, Graham JM Jr, Dobyns WB. Am J Med Genet. Feb 2012; 158A(2):269-291. https://www.ncbi.nlm.nih.gov/pubmed/22228622/.
          2. Jean-Baptiste Rivière et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. August 2012; 44(8):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408813/. Accessed 5/27/2016.
          3. Ghayda Mirzaa et al. De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nat Genet. April 6, 2014; 46(5):510-515. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004933/.
          4. Tohyama J. Megalencephaly and polymicrogyria with polydactyly syndrome. Pediatr Neurol. 2007;
          5. Pisano T. Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome: a new case with syndactyly. J Child Neurol. 2008;

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