Dandy-Walker syndrome
Encyclopedia
Dandy–Walker syndrome or Dandy–Walker complex, is a congenital brain
malformation involving the cerebellum
and the fluid filled spaces around it. A key feature of this syndrome is the partial or even complete absence of the part of the brain located between the two cerebellar hemispheres (cerebellar vermis
). The Dandy–Walker complex is a genetically
sporadic disorder that occurs one in every 25,000 live births, mostly in females.
; a partial or complete absence of the cerebellar vermis
, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull
. An increase in the size of the fluid spaces surrounding the brain as well as an increase in pressure may also be present. The syndrome can appear dramatically or develop unnoticed.
Symptoms, which often occur in early infancy, include slower motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure
such as irritability
, vomiting
and convulsion
s and signs of cerebellar dysfunction such as unsteadiness and lack of muscle coordination or jerky movements of the eye
s may occur. Other symptoms include increased head circumference, bulging at the back of the skull, problems with the nerves that control the eyes, face and neck, and abnormal breathing patterns.
Dandy–Walker syndrome is frequently associated with disorders of other areas of the central nervous system including absence of the corpus callosum
, the bundle of axons connecting the two cerebral hemisphere
s, and malformations of the heart
, face
, limb
s, finger
s and toe
s.
Prenatal diagnosis is possible with ultrasound
. Because the syndrome is associated with an increased risk for fetal karyotype
abnormalities, amniocentesis
can be offered after prenatal diagnosis. There is a relative contraindication of taking Warfarin
during pregnancy, as it is associated with an increased risk of Dandy–Walker syndrome if taken during the first trimester.
is enlarged and the tentorium
is in high position. There is partial or complete agenesis
of the cerebellar vermis
. There is also cystic dilation of the fourth ventricle
, which fills the posterior fossa
. This often involves hydrocephaly and complications due to associated genetic conditions, such as Spina Bifida
.
. The fourth ventricle
is only mildly enlarged and there is mild enlargement of the posterior fossa. The cerebellar vermis
is hypoplastic and has a variably sized cyst
space. This is caused by open communication of the posteroinferior fourth ventricle and the cisterna magna
through the enlarged vallecula
. Patients exhibit hydrocephalus
in 25% of cases and supratentorial CNS variances are uncommon, only present in 20% of cases. There is no torcular-lambdoid inversion, as usually seen in patients with the malformation. The third and lateral ventricles as well as the brain stem are normal.
s, both genetic syndromes
and genetic diseases
, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause
despite the widely-varying set of medical symptoms
that are clinically visible in the disorders. Dandy–Walker syndrome is one such disease, part of an emerging
class of diseases called ciliopathies
. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
, organelle
s which are present in many cellular types throughout the human
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia
, Bardet-Biedl syndrome
, polycystic kidney
and liver disease
, nephronophthisis
, Alstrom syndrome
, Meckel-Gruber syndrome and some forms of retinal degeneration
.
Genetic associations of the condition are being investigated.
A special tube (shunt) to reduce intracranial pressure may be placed inside the skull to control swelling.
Treatment may also consist of various therapies such as occupational therapy, physical therapy, speech therapy or specialized education. Services of a vision teacher may be helpful if the eyes are affected.
Parents of children with Dandy–Walker syndrome may benefit from genetic counseling if they intend to have more children.
Children with less severe symptoms may have normal intellectual development; children with severe malformation may have mental retardation. Longevity depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten life span.
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
malformation involving the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
and the fluid filled spaces around it. A key feature of this syndrome is the partial or even complete absence of the part of the brain located between the two cerebellar hemispheres (cerebellar vermis
Cerebellar vermis
The cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
). The Dandy–Walker complex is a genetically
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
sporadic disorder that occurs one in every 25,000 live births, mostly in females.
Presentation
The key features of this syndrome are an enlargement of the fourth ventricleFourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ventricle...
; a partial or complete absence of the cerebellar vermis
Cerebellar vermis
The cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...
. An increase in the size of the fluid spaces surrounding the brain as well as an increase in pressure may also be present. The syndrome can appear dramatically or develop unnoticed.
Symptoms, which often occur in early infancy, include slower motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
such as irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
and convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s and signs of cerebellar dysfunction such as unsteadiness and lack of muscle coordination or jerky movements of the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
s may occur. Other symptoms include increased head circumference, bulging at the back of the skull, problems with the nerves that control the eyes, face and neck, and abnormal breathing patterns.
Dandy–Walker syndrome is frequently associated with disorders of other areas of the central nervous system including absence of the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
, the bundle of axons connecting the two cerebral hemisphere
Cerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
s, and malformations of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, face
Face
The face is a central sense organ complex, for those animals that have one, normally on the ventral surface of the head, and can, depending on the definition in the human case, include the hair, forehead, eyebrow, eyelashes, eyes, nose, ears, cheeks, mouth, lips, philtrum, temple, teeth, skin, and...
, limb
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
s, finger
Finger
A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....
s and toe
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...
s.
Prenatal diagnosis is possible with ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
. Because the syndrome is associated with an increased risk for fetal karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
abnormalities, amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...
can be offered after prenatal diagnosis. There is a relative contraindication of taking Warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
during pregnancy, as it is associated with an increased risk of Dandy–Walker syndrome if taken during the first trimester.
Classification
The term Dandy–Walker represents not a single entity, but several abnormalities of brain development which coexist. There are, at present, three identified types of Dandy–Walker complexes. These represent closely associated forms of the disorder: DWS malformation, DWS mega cisterna magna and DWS variant.Malformation
The DWS malformation is the most severe presentation of the syndrome. The posterior fossaPosterior fossa
Posterior fossa may refer to:* Posterior cranial fossa* Posterior intercondyloid fossa...
is enlarged and the tentorium
Tentorium cerebelli
The tentorium cerebelli or cerebellar tentorium is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.-Anatomy:...
is in high position. There is partial or complete agenesis
Agenesis
In medicine, agenesis refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue...
of the cerebellar vermis
Cerebellar vermis
The cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
. There is also cystic dilation of the fourth ventricle
Fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ventricle...
, which fills the posterior fossa
Posterior fossa
Posterior fossa may refer to:* Posterior cranial fossa* Posterior intercondyloid fossa...
. This often involves hydrocephaly and complications due to associated genetic conditions, such as Spina Bifida
Spina bifida
Spina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through...
.
Variant
The third type is the variant, which is less severe than the malformation. This form (or forms) represents the most wide-ranging set of symptoms and outcomes of DWS. Many patients who do not fit into the two other categories of DWS are often labeled as variantVariant
Variant is a free cultural magazine based in Glasgow, Scotland, and founded in 1984. Available in both print and internet editions, it is distributed mainly though arts and cultural institutions through Britain and Ireland. Although nominally an arts and cultural bulletin, the magazine also deals...
. The fourth ventricle
Fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ventricle...
is only mildly enlarged and there is mild enlargement of the posterior fossa. The cerebellar vermis
Cerebellar vermis
The cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
is hypoplastic and has a variably sized cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
space. This is caused by open communication of the posteroinferior fourth ventricle and the cisterna magna
Cisterna magna
The cisterna magna is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain. The openings are collectively referred to as cisterns. The cisterna magna is located between the cerebellum and the dorsal surface of...
through the enlarged vallecula
Vallecula
-Types:There are a variety of valleculae in the human body, including one between the hemispheres of the brain, on the inferior surface of the cerebellum, in which the medulla oblongata is located...
. Patients exhibit hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
in 25% of cases and supratentorial CNS variances are uncommon, only present in 20% of cases. There is no torcular-lambdoid inversion, as usually seen in patients with the malformation. The third and lateral ventricles as well as the brain stem are normal.
Relation to other rare disorders: genetic ciliopathy
Until recently, the medical literature did not indicate a connection among many genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s, both genetic syndromes
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
and genetic diseases
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
despite the widely-varying set of medical symptoms
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
that are clinically visible in the disorders. Dandy–Walker syndrome is one such disease, part of an emerging
Emergence
In philosophy, systems theory, science, and art, emergence is the way complex systems and patterns arise out of a multiplicity of relatively simple interactions. Emergence is central to the theories of integrative levels and of complex systems....
class of diseases called ciliopathies
Ciliopathy
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosomes, it is possible for ciliopathies to be associated...
. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s which are present in many cellular types throughout the human
Human
Humans are the only living species in the Homo genus...
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia
Primary ciliary dyskinesia
Primary ciliary dyskinesia , also known as immotile ciliary syndrome or Kartagener Syndrome ', is a rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract and fallopian tube, and also of the flagella of sperm in...
, Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
, polycystic kidney
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
and liver disease
Polycystic liver disease
Polycystic liver disease usually describes the presence of multiple cysts scattered throughout normal liver tissue, in association with polycystic kidney disease.-Pathophysiology:Associations with PRKCSH and SEC63 have been described....
, nephronophthisis
Nephronophthisis
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease.The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.It is a form of...
, Alstrom syndrome
Alstrom syndrome
Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in...
, Meckel-Gruber syndrome and some forms of retinal degeneration
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
.
Genetic associations of the condition are being investigated.
Relation to PHACES syndrome
Recent research has found that Dandy–Walker syndrome often occurs in patients with PHACES syndrome.Treatment
Treatment for individuals with Dandy–Walker Syndrome generally consists of treating the associated problems, if needed.A special tube (shunt) to reduce intracranial pressure may be placed inside the skull to control swelling.
Treatment may also consist of various therapies such as occupational therapy, physical therapy, speech therapy or specialized education. Services of a vision teacher may be helpful if the eyes are affected.
Parents of children with Dandy–Walker syndrome may benefit from genetic counseling if they intend to have more children.
Prognosis
The spectrum of outcomes for Dandy–Walker syndrome is diverse. Mortality statistics are often compiled by neurologists who deal with worst-case outcomes, which thus reflect a high mortality rate, or grim prognosis – both pre- and postnatal – in DWS infants.Children with less severe symptoms may have normal intellectual development; children with severe malformation may have mental retardation. Longevity depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten life span.
External links
- Dandy–Walker Alliance, a non-profit organization of individuals directly and indirectly affected by Dandy–Walker
- Metry Phaces article in the Journal of Pediatrics, July 2001
- E-medicine webpage definition
- Hydrocephalus Association
- Dandy–Walker Malformation article from Pan Arab Journal of Neurosurgery
- Dandy–Walker Syndrome page at Medical College of Wisconsin website