Dandy-Walker malformation

Definition

Dandy-Walker malformation is a congenital (present at birth) condition involving several abnormalities in the development of the brain. The malformation appears to result from destructive processes, such as inflammation or trauma, which block the circulation of cerebrospinal fluid (CSF) inside the head after the brain has been formed in the embryo.

Description

Dandy-Walker malformation was first described in 1914 by Drs. Dandy and Blackfan. The disorder typically includes the following abnormalities in brain structure:

• Absence or incomplete formation of the vermis, the middle portion of the cerebellum, which is the part of the human brain that lies behind the two cerebral hemispheres.
• Enlargement of the fourth ventricle, one of the human brain's four interconnected ventricles (inner cavities or chambers) that produce cerebrospinal fluid (CSF). In Dandy-Walker malformation, the CSF cannot circulate freely through the ventricles and the rest of the central nervous system (CNS), so it builds up inside the fourth ventricle and causes it to enlarge.
• Cysts (sacs) containing CSF are formed in the posterior fossa, which is a hollow at the back of the skull that covers the cerebellum.
• Absence or incomplete formation of the three foramina (small openings or holes) in the fourth ventricle.

In Dandy-Walker malformation, the CSF produced by the ventricles of the brain is not fully reabsorbed by the body; thus, the excess fluid accumulates in the fourth ventricle and the posterior fossa. As cysts in these areas grow, pressure from the fluid rises, producing a condition known as obstructive, or non-communicating, hydrocephalus (excess fluid on the brain). This type of hydrocephalus develops in 90% of children diagnosed with Dandy-Walker malformation. The size of the head may or may not be affected by the fluid pressure.

Genetic profile

The genetic transmission of Dandy-Walker malformation is not fully understood because the disorder often occurs with other birth abnormalities including cleft palate, extra fingers (polydactyly ) or fingers joined together (syndactyly), cataracts, and malformations of the face or heart. An abnormality in the central nervous system that often occurs together with Dandy-Walker malformation is agenesis (absence or failure to develop) of the corpus callosum, the thick band of nerve fibers that joins the two cerebral hemispheres. It is not yet clear whether these and other abnormalities in CNS development are determined by the same gene or whether they are inherited separately.

Dandy-Walker malformation appears to be transmitted in some families in an autosomal, or X-linked, recessive pattern, which means that both parents have one copy of the changed (mutated) gene but do not have the malformation. These families have a high risk of recurrence of the malformation. Families in which there has been inbreeding among close relatives also appear to transmit Dandy-Walker in an autosomal recessive pattern. Several chromosomal abnormalities have been associated with Dandy-Walker.

Demographics

Dandy-Walker malformation is a rare disorder. It is estimated to occur in about 3% of children with hydrocephalus, which occurs in 1–2 per 1,000 births. It appears to affect both sexes equally. While there is no known association with specific races or ethnic groups, recent genetic case studies of Dandy-Walker malformation include cases from Argentina, Poland, Germany, Brazil, Austria, and Japan.

Signs and symptoms

Some signs of Dandy-Walker malformation may appear before birth. It is possible to detect hydrocephalus by ultrasound as early as 15-18 weeks after conception. A newborn with hydrocephalus may have difficulty breathing, dilated veins visible on the scalp, and rapid head growth. Infants with Dandy-Walker may be slow to develop motor (movement) skills, and may have abnormally large skulls as a result of the fluid pressure inside the head.

Older children with Dandy-Walker malformation may have symptoms associated with fluid pressure inside the head including vomiting, convulsions, and emotional irritability. If the cerebellum has been damaged, the child's sense of balance and coordination will be affected. About 20% of older children with Dandy-Walker have difficulty coordinating movements of the hands or feet (ataxia) or have involuntary jerking movements of the eyes (nystagmus). Developmental delays and mental retardation are more common. In some cases Dandy-Walker may be associated with an abnormal pituitary gland and delayed puberty. Other symptoms that sometimes appear in this group include unusually large head size, a bulge at the back of the head caused by fluid pressure in the posterior fossa, and abnormal breathing patterns.

Diagnosis

About 80% of children with Dandy-Walker malformation are diagnosed before the end of the first year, usually as a result of the signs of hydrocephalus. Following birth, the newborn's head circumference is measured to determine whether it has been enlarged by the development of cysts. As has already been mentioned, ultrasound screening before birth can detect some signs of hydrocephalus. Ultrasound screening is recommended if the family has a history of congenital neurologic abnormalities. Genetic counseling is recommended for parents who have already had a child with Dandy-Walker malformation as there is an increased risk that the malformation will reoccur in later pregnancies.

Imaging studies used to diagnose and monitor Dandy-Walker include:

• x rays of the skull to determine that the posterior fossa has been enlarged;
• CT scan or magnetic resonance imaging (MRI) tests to evaluate the size and shape of the fourth ventricle, the presence and size of the vermis, and the displacement of other parts of the brain by fluid pressure;
• cranial ultrasound to evaluate the size of the ventricle or to assess the progression of hydrocephalus; or
• transillumination, a technique that shines a strong light through an organ or body part to assist in diagnosis. The posterior fossa may be transilluminated as part of the differential diagnosis of Dandy-Walker.

Treatment and management

Treatment of Dandy-Walker malformation is usually focused on managing hydrocephalus when it is present. Hydrocephalus cannot be cured, but it can be treated surgically by placing a shunt in the ventricles of the brain to reduce fluid pressure. The shunt carries some of the CSF into another part of the body where it can be reabsorbed.

Another important part of managing Dandy-Walker is treatment of conditions or abnormalities associated with it—such as giving anticonvulsant medications for seizures or hormones to bring on puberty that has been delayed.

Prognosis

The prognosis for children with Dandy-Walker malformation is usually not encouraging because of the associated multiple abnormalities. Children with other congenital abnormalities occurring together with Dandy-Walker often do not survive. The affected person's chances of normal intellectual development depend on the severity of the malformation and the presence of other abnormalities.

Resources

BOOKS

Martin, John H., PhD. Neuroanatomy: Text and Atlas, 2nd ed. Norwalk, CT: Appleton & Lange, 1996.

"Neurologic Abnormalities." The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

PERIODICALS

Cavalcanti, D. P., and M. A. Salomao. "Dandy-Walker malformation with postaxial polydactyly: further evidence for autosomal recessive inheritance." American Journal of Medical Genetics 16 (July 1999): 183-184.

Kawame, H., et al. "Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature. Journal of Human Genetics 44, no. 4 (1999): 219-224.

Macmillin, M. D., et al. "Prenatal diagnosis of inverted duplicated 8p." American Journal of Medical Genetics 17 (July 2000): 94-98.

Marszal, E., et al. "Agenesis of corpus callosum: clinical description and etiology." Journal of Child Neurology 15, no. 6 (June 2000): 401-405.

Rittler, M., and E. E. Castilla. "Postaxial polydactyly and Dandy-Walker malformation. Further nosological comments." Clinical Genetics 56 (1999): 462-463.

Ulm, B., et al. "Isolated Dandy-Walker malformation: prenatal diagnosis in two consecutive pregnancies." American Journal of Perinatology 16, no. 2 (1999): 61-63.

von Kaisenberg, C. S., et al. "Absence of 9q22-9qter in trisomy 9 does not prevent a Dandy-Walker phenotype." American Journal of Medical Genetics 18 (December 2000): 425-428.

ORGANIZATIONS

Dandy-Walker Syndrome Network. 5030 142nd Path West, Apple Valley, MN 55124. (612) 423-4008.

Guardians of Hydrocephalus Research Foundation. 2618 Avenue Z, Brooklyn, NY 11235-2023. (718) 743-4473 or (800) 458-865. Fax: (718) 743-1171. ghrf2618@aol.com.

Hydrocephalus Association. 870 Market St. Suite 705, San Francisco, CA 94102. (415) 732-7040 or (888) 598-3789. (415) 732-7044. hydroassoc@aol.com. <http://neurosurgery.mgh.harvard.edu/ha>.

National Institute of Neurological Disorders and Stroke. 31 Center Drive, MSC 2540, Bldg. 31, Room 8806, Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

WEBSITES

Hydrocephalus Association. <http://www.HydroAssoc.org> or <http://www.neurosurgery.mgh.harvard.edu/ha>.

Rebecca J. Frey, PhD