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Diseases

Genetic and Rare Diseases Information Center (GARD)

Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome


Other Names for this Disease
  • MPPH syndrome
  • Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus
  • Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome
  • Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I would like to learn more about MPPH syndrome and how I can find other parents with children with this disorder.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome?

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.
Last updated: 5/27/2016

What are the signs and symptoms of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome?

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]
Last updated: 5/26/2016

What is polymicrogyria?

Polymicrogyria is a condition characterized by abnormal development of the brain before birth. Specifically, the surface of the brain develops too many folds which are unusually small. The signs and symptoms associated with the condition vary based on how much of the brain and which areas of the brain are affected; however, affected people may experience recurrent seizures (epilepsy); delayed development; crossed eyes; problems with speech and swallowing; and muscle weakness or paralysis. Bilateral forms (affecting both sides of the brain) tend to cause more severe neurological problems. Polymicrogyria can result from both genetic and environmental causes. It may occur as an isolated finding or as part of a syndrome. Treatment is based on the signs and symptoms present in each person.[6][7]
Last updated: 10/12/2015

What are the signs and symptoms of polymicrogyria?

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:[8][9]
  • Developmental delay
  • Crossed eyes
  • Epilepsy
  • Paralysis of the face, throat, and tongue
  • Difficulty with speech and swallowing
  • Drooling
Last updated: 5/25/2016

Can polymicrogyria be associated with other conditions?

Yes. Polymicrogyria may be an isolated occurrence or it may be a part of a larger condition, chromosome abnormality, and/or syndrome. “Syndrome” is a term used to describe a condition that is characterized by a particular collection of symptoms. Examples of associated syndromes, include Aicardi syndrome, Zellweger syndrome, and Smith-Lemli-Opitz syndrome.[8]
Last updated: 5/25/2016

What is megalencephaly?

Megalencephaly, also called macrencephaly, is a condition in which there is an abnormally large heavy brain. By definition, the brain weight is greater than average for the age and gender of the individual. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Megalencephaly is different from an increased head circumference or macrocephaly, which doesn't necessarily indicate abnormality.[10]

Last updated: 5/25/2016

What are the signs and symptoms of megalencephaly?

Megalencephaly may cause no symptoms or be associated with developmental delay, seizures, and neurological problems. Megalencephaly is more common in males than females.[10]
Last updated: 5/25/2016

Can megalencephaly be associated with other conditions?

Yes. Megalencephaly may be an isolated occurrence with normal cerebral structure, or associated with larger conditions or syndromes such as megalencephaly-capillary malformation syndromeleukodystrophies and neurofibromatosis.[10][11][12]
Last updated: 5/25/2016

What is polydactyly?

Polydactyly is a condition in which a person has more than five fingers per hand. Extra digits may be poorly developed and attached by a small stalk, or may be well-formed and have function.[13]
Last updated: 5/25/2016

Can polydactyly be associated with other conditions?

Yes. Polydactyly can occur on its own (e.g. familial polydactyly) or may be a part of a larger condition, chromosome abnormality, and/or syndrome. Examples of associated syndromes, include Carpenter syndrome, Ellis-van Creveld syndrome, Laurence-Moon-Biedl syndrome, Rubinstein-Taybi syndrome, and Smith-Lemli-Opitz syndrome. It can also occur in association with chromosomal abnormalities such as Trisomy 13.[13]
Last updated: 5/25/2016

What kind of polydactyly is typically seen in people with megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome?

People with MPPH syndrome have post axial polydactyly, meaning the extra digit is on the outside of the little toe(s) or finger(s), and often times involves both hands and feet.[12]
Last updated: 5/25/2016

What is hydrocephalus?

Hydrocephalus is a condition characterized by excessive accumulation of fluid in the brain. Although it was once known as "water on the brain," the "water" is actually cerebrospinal fluid (CSF) - clear fluid that surrounds the brain and spinal cord. Excess CSF builds up when it cannot drain from the brain due to a blockage in a passage through which the fluid normally flows.  This excess fluid causes an abnormal widening of spaces in the brain called ventricles; this can create harmful pressure on brain tissue. Symptoms vary with age, disease progression, and individual differences in tolerance to the condition. Hydrocephalus may be congenital (present at birth) or acquired. The causes are not fully understood; it may result from inherited genetic abnormalities or developmental disorders; complications of premature birth; diseases such as meningitis; tumors; traumatic head injury; or other causes. It is most often treated by surgically inserting a shunt system.[14]
Last updated: 8/22/2011

Can hydrocephalus be associated with other conditions?

Yes. Hydrocephalus can occur due to a number of causes including head injuries, strokes, and infections. It can also be a part of a larger condition, chromosome abnormality, and/or syndrome.[15]
Last updated: 5/25/2016

What causes megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome?

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]
Last updated: 5/27/2016

How can I find other parents with children with megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome?

We recognize that it can be a challenge to find other families with children with the same condition, particularly when the condition is very rare like MPPH syndrome. The following advocacy organizations and online networks for patients with rare conditions and their families may be helpful as you search for other parents. You can register your child's disease with these sites and search for other families and allow other families to find you. You may also use these resources to find families with children with symptoms similar to those that affect your child: 

RareShare is an online social hub dedicated to patients, families and healthcare professionals affected by rare medical disorders. Click on RareShare to learn more.

RareConnect provides a similar platform for patients, families, and patient organizations to connect. RareConnect is associated with the European Organization for Rare Diseases (EURORDIS). Click on RareConnect to learn more. 
Last updated: 5/26/2016

References
Other Names for this Disease
  • MPPH syndrome
  • Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus
  • Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome
  • Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.