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Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome

Last updated Jan. 7, 2019

Approved by: Maulik P. Purohit MD, MPH

Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus (MPPH) Syndrome is a disorder characterized by the presence of multiple birth defects and developmental delay.

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

  • Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus
  • Megalencephaly-Polymicrogyria-Postaxial Polydactyly-Hydrocephalus Syndrome
  • MPPH Syndrome

What is Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome? (Definition/Background Information)

  • Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus (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
  • 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
  • The diagnosis of MPPH syndrome is based on physical examination, imaging studies, and genetic testing
  • Treatment is based on the signs and symptoms present in each person

(Source: Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome? (Age and Sex Distribution)

  • Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome is a rare congenital disorder, with about 60 cases reported in the medical literature
  • The onset of disease symptoms may occur at birth or in infancy
  • Both genders may be affected
  • Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome? (Predisposing Factors)

  • A positive family history may be an important risk factor, since Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome can be inherited
  • Currently, no other risk factors have been clearly identified for this disorder

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 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome? (Etiology)

  • Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome may be caused by mutation(s) in PIK3R2, AKT3 or CCND2 gene
  • Each gene codes for proteins involved in an important cellular chemical signaling pathway, known as the PI3K-AKT-mTOR pathway. Causative mutation(s) in the 3 genes increase the activity of the respective proteins
    • The proper functioning of this pathway is crucial for growth and proliferation of cells in an organized manner, including cells in the brain
    • Mutations in the 3 genes leads to hyperactivation of this pathway, resulting in rapid and abnormal growth in brain cells (which begins in the fetal stages)
  • In the majority of cases, the disorder occurs as a result of de novo mutations in the causative genes during the formation of reproductive cells or early in the development of embryos. Most affected individuals, therefore, do not have a family history of the condition
  • In rare cases, the condition can be inherited in an autosomal dominant manner
  • Additionally, the condition can also occur due to germline mosaicism, in which an unaffected parent has mutations in the sperm or egg cells, which the child inherits. Somatic mosaicism may be another cause of this disorder, in which affected individuals carry mutations in some cells and not others

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome?

The signs and symptoms of Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome may include:

  • Polymicrogyria
  • Megalencephaly
  • Intellectual disability
  • Seizures
  • Polydactyly
  • 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)
    • Infantile spasms.

A wide variety of symptoms may be observed in people with polymicrogyria, depending on the areas of the brain implicated and whether or not it is part of a larger syndrome. Signs and symptoms may include:

  • Developmental delay
  • Crossed eyes
  • Epilepsy
  • Paralysis of the face, throat, and tongue
  • Difficulty with speech and swallowing
  • Drooling

(Source: Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome Diagnosed?

Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 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
  • 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 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome?

The complications of Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome may include:

  • Delayed speech development
  • Risk of falls and injury due to seizures

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

How is Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome Treated?

There is no cure for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome be Prevented?

Currently, Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome may not be preventable, since it is a genetic disorder.

  • 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 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome? (Outcomes/Resolutions)

  • The prognosis of Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
  • Individuals with mild conditions have better prognosis than those with severe symptoms and complications
  • Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome:

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


What are some Useful Resources for Additional Information?

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Jan. 7, 2019
Last updated: Jan. 7, 2019