The following information may help to address your question:
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?
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?
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 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.
[14] 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.
[14][15][16]
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.
[14][16] Congenital hydrocephalus can be an isolated malformation or be part of a syndrome where there are other associated malformations.
[14] 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.
[14][15][16]
Hydrocephalus may be subdivided according to the particular defect that exists in the brain and whether the cerebrospinal fluid pressure is high or normal:[14][17]
- 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:[14][17]
- 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.[14][18]
Last updated: 1/30/2018
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
We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please
contact us.
Warm regards,
GARD Information Specialist
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