Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome

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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

What is congenital hydrocephalus?

Congenital hydrocephalus is when a child is born with an excessive accumulation of cerebrospinal fluid (CSF) in the brain. CSF is a clear fluid that surrounds the brain and spinal cord. This excess fluid causes an abnormal widening of spaces in the brain called ventricles (ventriculomegalia) and can create a harmful pressure on brain tissue. Symptoms of hydrocephalus vary and may include an unusually large head with thin, transparent scalp, bulging forehead with increased spaces between the bones of the skull (fontanelles), and a downward gaze. Other symptoms may include seizures, abnormal reflexes, slow heartbeat and respiratory rate, headaches, vomiting, irritability, weakness, and visual problems.

It is caused by genetic and non-genetic factors. The most common cause of congenital hydrocephalus are variations (mutations) in the L1CAM gene, where there is a narrow passageway between the third and fourth ventricles (aqueductal stenosis). Other causes include mutations in many other genes, brain and/or spinal cord malformations, infections, bleeding inside the cavities of the brain (intraventricular hemorrhage), trauma, exposition to certain drugs (teratogens) or a congenital tumor of the brain. Congenital hydrocephalus can be an isolated malformation or be part of a syndrome where there are other associated malformations. It is most often treated by surgically inserting a shunt system to transport the excess CSF and allow for re-absorption. If left untreated, blindness and continuing mental deterioration may occur.

Hydrocephalus may be subdivided according to the particular defect that exists in the brain and whether the cerebrospinal fluid pressure is high or normal:

  • Communicating hydrocephalus is when there is no blockage (obstruction) in the ventricules but the fluid is not absorbed readily, or there is too much fluid to be absorbed.
  • Noncommunicating (obstructive) hydrocephalus is when there is a blockage of the CSF causing widening (dilation) of the pathways that are located upstream of the block, resulting in an increased pressure inside the brain.

There are also 2 other forms of hydrocephalus that usually affect only adults:

  • Normal-pressure hydrocephalus is where the ventricules are expanded but the pressure inside the nervous system is normal.
  • Hydrocephalus ex-vacuo occurs when stroke or traumatic injury cause damage to the brain and the brain tissue may shrink.

Hydrocephalus may also be classified in congenital or acquired. Acquired hydrocephalus develops at the time of birth or at some point afterward and may be caused by injury or disease.

Last updated on 05-01-20

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 on 05-01-20

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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

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 syndrome, leukodystrophies and neurofibromatosis.

Last updated on 05-01-20

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. 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.

Last updated on 05-01-20

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.

Last updated on 05-01-20

Name: The Arc of the United States 1825 K Street, NW Suite 1200
Washington, DC, DC, 20006, United States
Phone: +1-202-534-3700 Toll Free: 1-(800) 433-5255 Fax : +1-202-534-3731 Email: Url:
Name: PMG Awareness Organization 15642 Sand Canyon Avenue Unit 51235
Irvine, CA, 92619, United States
Phone: (949) 329-5975 Email: Url:

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