What is Dandy Walker syndrome

Dandy-Walker syndrome is a group of disorders that affect the development of the brain. The changes in brain development are present from birth (congenital). Dandy-Walker syndrome affects the formation of the area of the brain known as the cerebellum, which is responsible for coordinating movement, and the fluid-filled spaces around it. People with Dandy-Walker syndrome may have a portion of the brain called the cerebellar vermis that is smaller than expected (hypoplastic) or completely absent (aplastic). The cerebellar vermis is the area of the brain between the two halves of the cerebellum. People with Dandy-Walker syndrome have a larger than expected fourth ventricle of the brain. The fourth ventricle allows fluid to flow between the upper and lower areas of the brain and spinal cord. People with Dandy-Walker syndrome may have an enlarged portion of the base of the skull (posterior fossa) and cyst formation near the lowest part of the skull. An increase in the size and pressure of the fluid spaces surrounding the brain (hydrocephalus) may also be present. Dandy Walker syndrome is estimated to affect 1 in 10,000 to 30,000 newborns. Dandy-Walker syndrome may be more common in females than in males.

Dandy-Walker syndrome is a group of disorders that have overlapping symptoms. These disorders include:

• Dandy-Walker malformation (also known as Dandy-Walker syndrome): having a small cerebellar vermis, large fourth ventricle, and enlarged posterior fossa
• Isolated cerebellar vermis hypoplasia (sometimes known as Dandy-Walker variant): having a small cerebellar vermis without other features of Dandy-Walker syndrome
• Mega-cisterna magna: having an enlarged posterior fossa with a typically developed cerebellum. This may be a normal variant and may not cause any health problems.
• Posterior fossa arachnoid cyst: the development of a cyst on the posterior fossa without any other features of Dandy-Walker syndrome

Each of these disorders can have separate causes and different long-term outlooks. In order to provide families with more information about the specific developmental differences in the brain and the long-term outlook, a person with Dandy-Walker syndrome may be given a more specific diagnosis.

In some cases, Dandy-Walker syndrome is caused by an underlying genetic change. These genetic changes may cause Dandy-Walker syndrome alone, or they may cause Dandy-Walker syndrome as well as other health problems. In these situations, the syndrome can run in families. However, in most situations, Dandy-Walker syndrome is caused by a combination of genetic and environmental factors.

Dandy-Walker syndrome can appear dramatically or develop unnoticed. Symptoms, which often occur in early infancy, include slow motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure (pressure within the skull) such as irritability and vomiting, and signs of cerebellar dysfunction such as unsteadiness, lack of muscle coordination, or jerky movements of the eyes may occur. Other symptoms include increased head circumference, bulging at the back of the skull, abnormal breathing problems, and problems with the nerves that control the eyes, face and neck. Dandy-Walker syndrome is sometimes associated with disorders of other areas of the central nervous system, including absence of the area made up of nerve fibers connecting the two cerebral hemispheres (corpus callosum) and malformations of the heart, face, limbs, fingers and toes.

Dandy-Walker syndrome can be diagnosed by imaging of the brain such as ultrasound, CT scan, or MRI scan.

Treatment for individuals with Dandy-Walker syndrome generally consists of treating the associated problems, if needed. A surgical procedure called a ventriculoperitoneal shunt may be required to drain off excess fluid within the brain, which will reduce pressure inside the skull and improve symptoms. Treatment may also include various forms of therapy (physical therapy, to help keep muscle strength and flexibility, and occupational therapy, to learn new ways of performing daily activities) and specialized education.

Figure 1. Dandy-Walker syndrome

What is the difference between Dandy-Walker syndrome and Dandy-Walker variant?

Dandy-Walker syndrome refers to a developmental abnormality of the brain generally characterized by 3 main findings:

• cystic dilation (enlargement) of the fourth ventricle (one of the fluid-filled cavities within the brain)
• complete or partial agenesis (absent development) of the cerebellar vermis (structure between both sides of the cerebellum)
• enlargement of the posterior fossa (space at the underside of the skull containing the brainstem and cerebellum) with elevated tentorium

Dandy-Walker variant has been characterized as varying degrees of underdevelopment (hypoplasia) of the cerebellar vermis, without enlargement of the fourth ventricle or cisterna magna ¹⁾.

Dandy-Walker syndrome and Dandy-Walker variant have many similarities, so a clear-cut distinction on prenatal ultrasound may not always be possible. Furthermore, the exact diagnostic criteria for Dandy-Walker variant are unclear, and some experts suggest the term should no longer be used because it does not seem to be useful for prognosis ²⁾.

Fetal MRI can be used to better define abnormalities in the fetal brain and to rule out other conditions that may look like a form Dandy-Walker on ultrasound exams. MRI and/or ultrasound after birth can be used to confirm the condition and diagnose any complications affecting the baby. An expert fetal neurological opinion is important because the long-term outcome for conditions that can resemble Dandy-Walker syndrome may be much different than in cases of Dandy-Walker malformation ³⁾.

Can both Dandy-Walker syndrome and Dandy-Walker variant be associated with other abnormalities?

Yes, both Dandy-Walker syndrome and Dandy Walker variant can be associated with central nervous system (CNS) syndromes, non-CNS syndromes, extra or missing chromosomes (aneuploidy), and poor neurological outcome. Because of this, some experts feel there is no role in differentiating the two. While many have tried to distinguish between the two to better define the prognosis for an affected fetus, it is unclear how useful this is in clinical practice ⁴⁾.

Dandy Walker syndrome has been known to occur in single-gene disorders (those caused by mutations in a single gene), chromosome abnormalities, environmentally-induced syndromes, or with other abnormalities. In one series of 50 cases of Dandy Walker syndrome and 49 cases of Dandy Walker variant, the incidence of additional CNS and non-CNS anomalies, and the incidence of chromosome abnormalities, were similar in both groups. In a different study of 17 cases of only Dandy Walker variant, 4 fetuses had ventriculomegaly and 3 had agenesis of the corpus callosum. Almost half of the affected fetuses had other non-CNS abnormalities, including congenital heart defects, gastrointestinal syndromes, renal (kidney) syndromes, and intrahepatic (liver) calcifications. However, another study of 19 cases of Dandy Walker variant (diagnosed strictly as isolated inferior vermian hypoplasia by fetal MRI) found near-normal outcome.[2] This would indicate the importance of using strict criteria for prenatal diagnosis ⁵⁾.

If a diagnosis of Dandy Walker syndrome or Dandy Walker variant is suspected in a fetus, a fetal MRI and consultation with an expert in fetal neurology is recommended.

When does the cerebellar vermis develop in a fetus, and when can a problem be diagnosed?

The development of the cerebellar vermis begins during the 9th week of gestation, and the entire vermis and cerebellum may be fully formed by the end of the 15th week of gestation. Some experts have noted that it may be fully formed by the end of 16 weeks gestation ⁶⁾. However, while Dandy Walker syndrome has been diagnosed in the first trimester, a false-positive diagnosis can be made at gestational ages of less than 18 weeks. Experts have noted that prenatal diagnosis of cerebellar malformations, particularly subtle findings such as Dandy-Walker variant, should not be made at less than 18 weeks gestation because it is possible that the development of the cerebellar vermis is incomplete ⁷⁾. Even after 18 weeks gestation, there are limitations in defining the presence or extent of defects in the cerebellum and/or vermis ⁸⁾. The diagnostic criteria for Dandy-Walker variant remain unclear, and the diagnosis does not appear to predict the final outcome ⁹⁾.

What testing is available for a fetus who may have Dandy-Walker variant?

Prenatal diagnosis for a fetus suspected of having a form of Dandy Walker syndrome can be challenging ¹⁰⁾. Prenatal ultrasounds and invasive genetic testing via amniocentesis or chorionic villus sampling have the ability to identify non-CNS anomalies and chromosome abnormalities. However, the accuracy of ultrasound in detecting all forms of Dandy Walker syndrome and more subtle CNS anomalies is less known. There remains a discrepancy between prenatal ultrasound and postnatal diagnosis in Dandy-Walker variant. Postnatal imaging is generally used to confirm the diagnosis ¹¹⁾.

Fetal MRI can be used to better define abnormalities in the fetal brain and to rule out other conditions that may look like a form of Dandy-Walker on ultrasound exams. MRI and/or ultrasound after birth can be used to confirm the condition and diagnose any complications affecting the baby. An expert fetal neurological opinion is important because the long-term outcome for conditions that can resemble a Dandy-Walker malformation may be much different than in cases of Dandy-Walker malformation ¹²⁾.

People with specific questions about prenatal imaging and testing for a form of Dandy-Walker complex should speak with a fetal neurologist and/or a genetics professional who specializes in prenatal care.

Dandy Walker syndrome causes

Experts still do not fully understand the causes of classic Dandy-Walker syndrome and its variants. In many cases, a specific cause cannot be identified. Potential causes include:

• Chromosomal defects that affect fetal brain development
• Certain viral infections in the mother that pass to the developing baby
• Exposure of the unborn baby to certain toxins or medications
• Maternal diabetes

In most cases, the exact cause of Dandy-Walker syndrome is unknown. It is thought that most cases are caused by a combination of genetic and environmental factors that affect early development before birth. In some cases, exposures that occur during pregnancy, such as a pregnant woman having diabetes or an infection such as rubella, are thought to cause an increased risk for the developing baby to have Dandy-Walker syndrome.

In some cases, Dandy-Walker syndrome is caused by an underlying genetic change. Dandy-Walker syndrome has also been associated with many chromosomal abnormalities. Dandy-Walker syndrome can be a feature of some conditions in which there is an extra copy of one chromosome in each cell (trisomy). Dandy-Walker syndrome most often occurs in people with trisomy 18 (an extra copy of chromosome 18), but can also occur in people with trisomy 13, trisomy 21, or trisomy 9. This condition can also be associated with missing (deletions) or copied (duplications) pieces of certain chromosomes. Dandy-Walker syndrome can also be a feature of genetic syndromes that are caused by mutations in specific genes. However, the brain malformations associated with Dandy-Walker syndrome often occur as an isolated feature (not associated with other health problems), and in these cases the cause is frequently unknown.

Dandy-Walker syndrome can also occur as a symptom of another genetic syndrome. For example, people with Dandy-Walker syndrome may have a change in a gene that causes them to develop Dandy-Walker syndrome as well as other health problems. Researchers are currently learning more about genes in which changes (pathogenic variants or mutations) can cause Dandy-Walker syndrome.

Dandy Walker syndrome inheritance pattern

Most cases of Dandy Walker syndrome are sporadic, meaning they occur in people with no history of Dandy Walker syndrome in their family. The cause of most cases of Dandy Walker syndrome remains unknown. A small percentage of people with Dandy Walker syndrome may have other family members with the Dandy Walker syndrome, but it is not clear how the Dandy Walker syndrome is inherited ¹³⁾. When the Dandy Walker syndrome is not thought to be caused by a single genetic change (pathogenic variant or mutation), the risk for a sibling to have the complex is between 1-5% ¹⁴⁾.

When Dandy Walker syndrome is caused by an underlying genetic syndrome, the chance for family members to have the Dandy Walker syndrome as well depends on the inheritance pattern of the underlying syndrome ¹⁵⁾.

Dandy Walker syndrome symptoms

The signs and symptoms of Dandy-Walker syndrome may depend on the age of the person who has the Dandy-Walker syndrome. In the majority of individuals with Dandy-Walker syndrome, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have an increase in the size and pressure of fluid spaces surrounding the brain (hydrocephalus) that may cause increased head size (macrocephaly) and bulging at the back of the skull. In some cases, the increased pressure on the brain can cause breathing problems, seizures, and difficulty controlling the movements of the eyes, face, and neck. About half of people with Dandy-Walker syndrome have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker syndrome often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker syndrome may experience muscle stiffness (spasticity), low muscle tone (hypotonia) and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition.

Children with Dandy-Walker syndrome might meet developmental milestones such as sitting up or walking later than expected (developmental delay). In older children who have Dandy-Walker syndrome, signs and symptoms may include irritability, vomiting, jerky movements of the eyes (nystagmus), and trouble coordinating movements (ataxia). These symptoms may develop slowly or appear suddenly.

In some cases, Dandy-Walker syndrome can be a sign of a separate underlying genetic syndrome. Therefore, some people with Dandy-Walker syndrome have other health problems or differences from birth that can affect other parts of the brain as well as the heart, face, limbs, fingers, and toes.

Symptoms of Dandy-Walker syndrome usually appear by age 1. These symptoms may include:

• Developmental delays in motor and language skills such as sitting up, walking, and talking
• Poor muscle tone, balance, and coordination
• Problems with eye movement, mainly jerky eye movement
• Vision and hearing impairment
• Seizures

Hydrocephalus complicates the majority of Dandy-Walker syndrome. Symptoms of hydrocephalus include:

• Abnormally rapid head growth
• Irritability
• Vomiting
• Excessive sleepiness

Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms.

Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features.

In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition.

Dandy Walker syndrome diagnosis

Your physician may detect Dandy-Walker syndrome in your baby with a fetal high-resolution (level II) ultrasound during the second or third trimester. Your doctor may refer you to our Fetal Medicine Institute for further testing to evaluate your baby’s condition. Tests may include:

• Fetal MRI to help confirm the diagnosis and rule out other conditions (e.g., arachnoid cysts, Blake’s pouch cysts, vermian hypoplasia, mega cisterna magna) that look like Dandy-Walker syndrome on ultrasound tests.
• MRI after birth to confirm the condition and diagnose any complications affecting your baby
• Ultrasound after birth to confirm the condition and diagnose any complications affecting your baby

Fetal MRI is an advanced, high-resolution imaging test that gives the best information about the underlying cause and the best picture of the rest of the baby’s brain. Obtaining a MRI scan and an expert fetal neurological opinion is important because the long-term outcome for conditions resembling Dandy-Walker malformations may be much better than in cases of Dandy-Walker syndrome.

Dandy Walker syndrome ultrasound

Dandy Walker syndrome and Dandy Walker variant have many similarities, so a clear-cut distinction on prenatal ultrasound may not always be possible. Furthermore, the exact diagnostic criteria for Dandy Walker variant are unclear, and some experts suggest the term should no longer be used because it does not seem to be useful for prognosis ¹⁶⁾.

Fetal MRI can be used to better define abnormalities in the fetal brain and to rule out other conditions that may look like a form Dandy Walker on ultrasound exams. MRI and/or ultrasound after birth can be used to confirm the condition and diagnose any complications affecting the baby. An expert fetal neurological opinion is important because the long-term outcome for conditions that can resemble Dandy Walker syndrome may be much different than in cases of Dandy Walker syndrome ¹⁷⁾.

Dandy Walker syndrome treatment

The main course of treatment for Dandy-Walker syndrome is to manage any complications that may arise. Treatment options may include:

• Medications to control seizures
• Speech therapy to help with speech and language development
• Physical therapy to improve muscle strength and coordination
• Surgical insertion of a ventriculoperitoneal shunt in cases of severe or worsening hydrocephalus
• Occupational therapy to help build self-care and mobility skills such as eating, getting dressed, and walking
• Special education as necessary for cognitive and learning problems

Treatment for Dandy-Walker syndrome is focused on relieving any pressure on the brain that is caused by the brain malformations. If there is excess fluid in the brain, a doctor may perform a surgery to place a ventriculoperitoneal shunt in the brain, which allows for the excess fluid to be drained. This can relieve the pressure in the brain and reduce some symptoms of Dandy-Walker syndrome. Medications can be used to help control seizures. Other symptoms of Dandy-Walker syndrome such as developmental delay or trouble coordinating movements may be treated with occupational therapy or physical therapy. Some children with Dandy-Walker syndrome may require additional help in school such as special education classes.

Dandy Walker syndrome prognosis

The effect of Dandy-Walker Syndrome on intellectual development is variable, with some children having normal cognition and others never achieving normal intellectual development even when the excess fluid buildup is treated early and correctly. Longevity depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten life span.

Dandy Walker syndrome life expectancy

The long-term outlook for people with Dandy-Walker syndrome depends on the symptoms that are caused by the changes in the structures of the brain. The long-term outlook also depends on whether Dandy-Walker syndrome occurs alone (isolated) or whether there is an underlying genetic syndrome that may cause other health problems. Because the differences in brain structure and the presence of an underlying genetic syndrome may affect the signs and symptoms or life expectancy that a person has, it may be difficult to predict the long-term outlook for people who have Dandy-Walker syndrome ¹⁸⁾.

Some people with Dandy-Walker syndrome may have physical disabilities or intellectual disabilities. In most cases, infants who have isolated Dandy-Walker variant are more likely to have normal outcomes in the newborn period ¹⁹⁾.