Cephalic disorders are congenital conditions that stem from damage to,
or abnormal development of, the budding nervous system. Cephalic is a term
that means "head" or "head end of the body." Congenital means the disorder
is present at, and usually before, birth. Although there are many
congenital developmental disorders, this fact sheet briefly describes only
cephalic conditions.
Cephalic disorders are not necessarily caused by a single factor, but
may be influenced by hereditary or genetic conditions, or by environmental
exposures during pregnancy such as medication taken by the mother,
maternal infection, or exposure to radiation. Some cephalic disorders
occur when the cranial sutures (the fibrous joints that connect the bones
of the skull) join prematurely. Most cephalic disorders are caused by a
disturbance that occurs very early in the development of the fetal nervous
system.
The human nervous system develops from a small, specialized plate of
cells on the surface of the embryo. Early in development, this plate of
cells forms the neural tube, a narrow sheath that closes between the third
and fourth weeks of pregnancy to form the brain and spinal cord of the
embryo. Four main processes are responsible for the development of the
nervous system: cell proliferation, the process in which nerve cells
divide to form new generations of cells; cell migration, the process in
which nerve cells move from their place of origin to the place where they
will remain for life; cell differentiation, the process during which cells
acquire individual characteristics; and cell death, a natural process in
which cells die. Understanding the normal development of the human nervous
system, one of the research priorities of the National Institute of
Neurological Disorders and Stroke, may lead to a better understanding of
cephalic disorders.
Damage to the developing nervous system is a major cause of chronic,
disabling disorders and, sometimes, death in infants, children, and even
adults. The degree to which damage to the developing nervous system harms
the mind and body varies enormously. Many disabilities are mild enough to
allow those afflicted to eventually function independently in society.
Others are not. Some infants, children, and adults die, others remain
totally disabled, and an even larger population is partially disabled,
functioning well below normal capacity throughout life.
ANENCEPHALY is a neural tube defect that occurs when the
cephalic (head) end of the neural tube fails to close, usually between the
23rd and 26th days of pregnancy, resulting in the absence of a major
portion of the brain, skull, and scalp. Infants with this disorder are
born without a forebrain - the largest part of the brain consisting mainly
of the cerebrum, which is responsible for thinking and coordination. The
remaining brain tissue is often exposed - not covered by bone or skin.
Infants born with anencephaly are usually blind, deaf, unconscious, and
unable to feel pain. Although some individuals with anencephaly may be
born with a rudimentary brainstem, the lack of a functioning cerebrum
permanently rules out the possibility of ever gaining consciousness.
Reflex actions such as respiration (breathing) and responses to sound or
touch may occur. The disorder is one of the most common disorders of the
fetal central nervous system. Approximately 1,000 to 2,000 American babies
are born with anencephaly each year. The disorder affects females more
often than males.
The cause of anencephaly is unknown. Although it is believed that the
mother's diet and vitamin intake may play a role, scientists agree that
many other factors are also involved.
There is no cure or standard treatment for anencephaly and the
prognosis for affected individuals is poor. Most infants do not survive
infancy. If the infant is not stillborn, then he or she will usually die
within a few hours or days after birth. Anencephaly can often be diagnosed
before birth through an ultrasound examination.
Recent studies have shown that the addition of folic acid to the diet
of women of child-bearing age may significantly reduce the incidence of
neural tube defects. Therefore it is recommended that all women of
child-bearing age consume 0.4 mg of folic acid daily.
COLPOCEPHALY is a disorder in which there is an abnormal
enlargement of the occipital horns - the posterior or rear portion of the
lateral ventricles (cavities or chambers) of the brain. This enlargement
occurs when there is an underdevelopment or lack of thickening of the
white matter in the posterior cerebrum. Colpocephaly is characterized by
microcephaly (abnormally small head) and mental retardation. Other
features may include motor abnormalities, muscle spasms, and seizures.
Although the cause is unknown, researchers believe that the disorder
results from an intrauterine disturbance that occurs between the second
and sixth months of pregnancy. Colpocephaly may be diagnosed late in
pregnancy, although it is often misdiagnosed as hydrocephalus (excessive
accumulation of cerebrospinal fluid in the brain). It may be more
accurately diagnosed after birth when signs of mental retardation,
microcephaly, and seizures are present.
There is no definitive treatment for colpocephaly. Anticonvulsant
medications can be given to prevent seizures, and doctors try to prevent
contractures (shrinkage or shortening of muscles). The prognosis for
individuals with colpocephaly depends on the severity of the associated
conditions and the degree of abnormal brain development. Some children
benefit from special education.
HOLOPROSENCEPHALY is a disorder characterized by the failure of
the prosencephalon (the forebrain of the embryo) to develop. During normal
development the forebrain is formed and the face begins to develop in the
fifth and sixth weeks of pregnancy. Holoprosencephaly is caused by a
failure of the embryo's forebrain to divide to form bilateral cerebral
hemispheres (the left and right halves of the brain), causing defects in
the development of the face and in brain structure and function.
There are three classifications of holoprosencephaly. Alobar
holoprosencephaly, the most serious form in which the brain fails to
separate, is usually associated with severe facial anomalies. Semilobar
holoprosencephaly, in which the brain's hemispheres have a slight tendency
to separate, is an intermediate form of the disease. Lobar
holoprosencephaly, in which there is considerable evidence of separate
brain hemispheres, is the least severe form. In some cases of lobar
holoprosencephaly, the patient's brain may be nearly normal.
Holoprosencephaly, once called arhinencephaly, consists of a spectrum
of defects or malformations of the brain and face. At the most severe end
of this spectrum are cases involving serious malformations of the brain,
malformations so severe that they are incompatible with life and often
cause spontaneous intrauterine death. At the other end of the spectrum are
individuals with facial defects - which may affect the eyes, nose, and
upper lip - and normal or near-normal brain development. Seizures and
mental retardation may occur.
The most severe of the facial defects (or anomalies) is cyclopia, an
abnormality characterized by the development of a single eye, located in
the area normally occupied by the root of the nose, and a missing nose or
a nose in the form of a proboscis (a tubular appendage) located above the
eye.
Ethmocephaly is the least common facial anomaly. It consists of a
proboscis separating narrow-set eyes with an absent nose and
microphthalmia (abnormal smallness of one or both eyes). Cebocephaly,
another facial anomaly, is characterized by a small, flattened nose with a
single nostril situated below incomplete or underdeveloped closely set
eyes.
The least severe in the spectrum of facial anomalies is the median
cleft lip, also called premaxillary agenesis.
Although the causes of most cases of holoprosencephaly remain unknown,
researchers know that approximately one-half of all cases have a
chromosomal cause. Such chromosomal anomalies as Patau's syndrome (trisomy
13) and Edwards' syndrome (trisomy 18) have been found in association with
holoprosencephaly. There is an increased risk for the disorder in infants
of diabetic mothers.
There is no treatment for holoprosencephaly and the prognosis for
individuals with the disorder is poor. Most of those who survive show no
significant developmental gains. For children who survive, treatment is
symptomatic. It is possible that improved management of diabetic
pregnancies may help prevent holoprosencephaly, however there is no means
of primary prevention.
HYDRANENCEPHALY is a rare condition in which the cerebral
hemispheres are absent and replaced by sacs filled with cerebrospinal
fluid. Usually the cerebellum and brainstem are formed normally. An infant
with hydranencephaly may appear normal at birth. The infant's head size
and spontaneous reflexes such as sucking, swallowing, crying, and moving
the arms and legs may all seem normal. However, after a few weeks the
infant usually becomes irritable and has increased muscle tone
(hypertonia). After several months of life, seizures and hydrocephalus may
develop. Other symptoms may include visual impairment, lack of growth,
deafness, blindness, spastic quadriparesis (paralysis), and intellectual
deficits.
Hydranencephaly is an extreme form of porencephaly (a rare disorder,
discussed later in this fact sheet, characterized by a cyst or cavity in
the cerebral hemispheres) and may be caused by vascular insult or
injuries, infections, or traumatic disorders after the 12th week of
pregnancy.
Diagnosis may be delayed for several months because the infant's early
behavior appears to be relatively normal. Transillumination, an
examination in which light is passed through body tissues, usually
confirms the diagnosis. Some infants may have additional abnormalities at
birth including seizures, myoclonus (involuntary sudden, rapid jerks), and
respiratory problems.
There is no standard treatment for hydranencephaly. Treatment is
symptomatic and supportive. Hydrocephalus may be treated with a shunt.
The outlook for children with hydranencephaly is poor. Death generally
occurs before age 1.
INIENCEPHALY is a rare neural tube defect that combines extreme
retroflexion (backward bending) of the head with severe defects of the
spine. The affected infant tends to be short, with a disproportionately
large head. Diagnosis can be made immediately after birth because the head
is so severely retroflexed that the face looks upward. The skin of the
face is connected directly to the skin of the chest and the scalp is
directly connected to the skin of the back. Generally, the neck is
absent.
Most individuals with iniencephaly have other associated anomalies such
as anencephaly, cephalocele (a disorder in which part of the cranial
contents protrudes from the skull), hydrocephalus, cyclopia, absence of
the mandible (lower jaw bone), cleft lip and palate, cardiovascular
disorders, diaphragmatic hernia, and gastrointestinal malformation. The
disorder is more common among females.
The prognosis for those with iniencephaly is extremely poor. Newborns
with iniencephaly seldom live more than a few hours. The distortion of the
fetal body may also pose a danger to the mother's life.
LISSENCEPHALY, which literally means "smooth brain," is a rare
brain formation disorder characterized by microcephaly and the lack of
normal convolutions (folds) in the brain. It is caused by defective
neuronal migration, the process in which nerve cells move from their place
of origin to their permanent location.
The surface of a normal brain is formed by a complex series of folds
and grooves. The folds are called gyri or convolutions, and the grooves
are called sulci. In children with lissencephaly, the normal convolutions
are absent or only partly formed, making the surface of the brain smooth.
Symptoms of the disorder may include unusual facial appearance,
difficulty swallowing, failure to thrive, and severe psychomotor
retardation. Anomalies of the hands, fingers, or toes, muscle spasms, and
seizures may also occur.
Lissencephaly may be diagnosed at or soon after birth. Diagnosis may be
confirmed by ultrasound, computed tomography (CT), or magnetic resonance
imaging (MRI).
Lissencephaly may be caused by intrauterine viral infections or viral
infections in the fetus during the first trimester, insufficient blood
supply to the baby's brain early in pregnancy, or a genetic disorder.
There are two distinct genetic causes of lissencephaly - X-linked and
chromosome 17-linked.
The spectrum of lissencephaly is only now becoming more defined as
neuroimaging and genetics has provided more insights into migration
disorders. Other causes which have not yet been identified are likely as
well.
Lissencephaly may be associated with other diseases including isolated
lissencephaly sequence, Miller-Dieker syndrome, and Walker-Warburg
syndrome.
Treatment for those with lissencephaly is symptomatic and depends on
the severity and locations of the brain malformations. Supportive care may
be needed to help with comfort and nursing needs. Seizures may be
controlled with medication and hydrocephalus may require shunting. If
feeding becomes difficult, a gastrostomy tube may be considered.
The prognosis for children with lissencephaly varies depending on the
degree of brain malformation. Many individuals show no significant
development beyond a 3- to 5-month-old level. Some may have near-normal
development and intelligence. Many will die before the age of 2.
Respiratory problems are the most common causes of death.
MEGALENCEPHALY, also called macrencephaly, is a condition in
which there is an abnormally large, heavy, and usually malfunctioning
brain. By definition, the brain weight is greater than average for the age
and gender of the infant or child. Head enlargement may be evident at
birth or the head may become abnormally large in the early years of life.
Megalencephaly is thought to be related to a disturbance in the
regulation of cell reproduction or proliferation. In normal development,
neuron proliferation - the process in which nerve cells divide to form new
generations of cells - is regulated so that the correct number of cells is
formed in the proper place at the appropriate time.
Symptoms of megalencephaly may include delayed development, convulsive
disorders, corticospinal (brain cortex and spinal cord) dysfunction, and
seizures. Megalencephaly affects males more often than females.
The prognosis for individuals with megalencephaly largely depends on
the underlying cause and the associated neurological disorders. Treatment
is symptomatic. Megalencephaly may lead to a condition called macrocephaly
(defined later in this fact sheet). Unilateral megalencephaly or
hemimegalencephaly is a rare condition characterized by the enlargement of
one-half of the brain. Children with this disorder may have a large,
sometimes asymmetrical head. Often they suffer from intractable seizures
and mental retardation. The prognosis for those with hemimegalencephaly is
poor.
MICROCEPHALY is a neurological disorder in which the
circumference of the head is smaller than average for the age and gender
of the infant or child. Microcephaly may be congenital or it may develop
in the first few years of life. The disorder may stem from a wide variety
of conditions that cause abnormal growth of the brain, or from syndromes
associated with chromosomal abnormalities.
Infants with microcephaly are born with either a normal or reduced head
size. Subsequently the head fails to grow while the face continues to
develop at a normal rate, producing a child with a small head, a large
face, a receding forehead, and a loose, often wrinkled scalp. As the child
grows older, the smallness of the skull becomes more obvious, although the
entire body also is often underweight and dwarfed. Development of motor
functions and speech may be delayed. Hyperactivity and mental retardation
are common occurrences, although the degree of each varies. Convulsions
may also occur. Motor ability varies, ranging from clumsiness in some to
spastic quadriplegia in others.
Generally there is no specific treatment for microcephaly. Treatment is
symptomatic and supportive.
In general, life expectancy for individuals with microcephaly is
reduced and the prognosis for normal brain function is poor. The prognosis
varies depending on the presence of associated abnormalities.
PORENCEPHALY is an extremely rare disorder of the central
nervous system involving a cyst or cavity in a cerebral hemisphere. The
cysts or cavities are usually the remnants of destructive lesions, but are
sometimes the result of abnormal development. The disorder can occur
before or after birth.
Porencephaly most likely has a number of different, often unknown
causes, including absence of brain development and destruction of brain
tissue. The presence of porencephalic cysts can sometimes be detected by
transillumination of the skull in infancy. The diagnosis may be confirmed
by CT, MRI, or ultrasonography.
More severely affected infants show symptoms of the disorder shortly
after birth, and the diagnosis is usually made before age 1. Signs may
include delayed growth and development, spastic paresis (slight or
incomplete paralysis), hypotonia (decreased muscle tone), seizures (often
infantile spasms), and macrocephaly or microcephaly.
Individuals with porencephaly may have poor or absent speech
development, epilepsy, hydrocephalus, spastic contractures (shrinkage or
shortening of muscles), and mental retardation. Treatment may include
physical therapy, medication for seizure disorders, and a shunt for
hydrocephalus. The prognosis for individuals with porencephaly varies
according to the location and extent of the lesion. Some patients with
this disorder may develop only minor neurological problems and have normal
intelligence, while others may be severely disabled. Others may die before
the second decade of life.
SCHIZENCEPHALY is a rare developmental disorder characterized by
abnormal slits, or clefts, in the cerebral hemispheres. Schizencephaly is
a form of porencephaly. Individuals with clefts in both hemispheres, or
bilateral clefts, are often developmentally delayed and have delayed
speech and language skills and corticospinal dysfunction. Individuals with
smaller, unilateral clefts (clefts in one hemisphere) may be weak on one
side of the body and may have average or near-average intelligence.
Patients with schizencephaly may also have varying degrees of
microcephaly, mental retardation, hemiparesis (weakness or paralysis
affecting one side of the body), or quadriparesis (weakness or paralysis
affecting all four extremities), and may have reduced muscle tone
(hypotonia). Most patients have seizures and some may have
hydrocephalus.
In schizencephaly, the neurons border the edge of the cleft implying a
very early disruption in development. There is now a genetic origin for
one type of schizencephaly. Causes of this type may include environmental
exposures during pregnancy such as medication taken by the mother,
exposure to toxins, or a vascular insult. Often there are associated
heterotopias (isolated islands of neurons) which indicate a failure of
migration of the neurons to their final position in the brain.
Treatment for individuals with schizencephaly generally consists of
physical therapy, treatment for seizures, and, in cases that are
complicated by hydrocephalus, a shunt.
The prognosis for individuals with schizencephaly varies depending on
the size of the clefts and the degree of neurological deficit.
ACEPHALY literally means absence of the head. It is a much rarer
condition than anencephaly. The acephalic fetus is a parasitic twin
attached to an otherwise intact fetus. The acephalic fetus has a body but
lacks a head and a heart; the fetus's neck is attached to the normal twin.
The blood circulation of the acephalic fetus is provided by the heart of
the twin. The acephalic fetus can not exist independently of the fetus to
which it is attached.
EXENCEPHALY is a condition in which the brain is located outside
of the skull. This condition is usually found in embryos as an early stage
of anencephaly. As an exencephalic pregnancy progresses, the neural tissue
gradually degenerates. It is unusual to find an infant carried to term
with this condition because the defect is incompatible with survival.
MACROCEPHALY is a condition in which the head circumference is
larger than average for the age and gender of the infant or child. It is a
descriptive rather than a diagnostic term, and is a characteristic of a
variety of disorders. Macrocephaly also may be inherited. Although one
form of macrocephaly may be associated with mental retardation, in
approximately one-half of cases mental development is normal. Macrocephaly
may be caused by an enlarged brain or hydrocephalus. It may be associated
with other disorders such as dwarfism, neurofibromatosis, and tuberous
sclerosis.
MICRENCEPHALY is a disorder characterized by a small brain and
may be caused by a disturbance in the proliferation of nerve cells.
Micrencephaly may also be associated with maternal problems such as
alcoholism, diabetes, or rubella (German measles). A genetic factor may
play a role in causing some cases of micrencephaly. Affected newborns
generally have striking neurological defects and seizures. Severely
impaired intellectual development is common, but disturbances in motor
functions may not appear until later in life.
OCTOCEPHALY is a lethal condition in which the primary feature
is agnathia - a developmental anomaly characterized by total or virtual
absence of the lower jaw. The condition is considered lethal because of a
poorly functioning airway. In octocephaly, agnathia may occur alone or
together with holoprosencephaly.
Another group of less common cephalic disorders are the craniostenoses.
Craniostenoses are deformities of the skull caused by the premature fusion
or joining together of the cranial sutures. Cranial sutures are fibrous
joints that join the bones of the skull together. The nature of these
deformities depends on which sutures are affected.
BRACHYCEPHALY occurs when the coronal suture fuses prematurely,
causing a shortened front-to-back diameter of the skull. The coronal
suture is the fibrous joint that unites the frontal bone with the two
parietal bones of the skull. The parietal bones form the top and sides of
the skull.
OXYCEPHALY is a term sometimes used to describe the premature
closure of the coronal suture plus any other suture, or it may be used to
describe the premature fusing of all sutures. Oxycephaly is the most
severe of the craniostenoses.
PLAGIOCEPHALY results from the premature unilateral fusion
(joining of one side) of the coronal or lambdoid sutures. The lambdoid
suture unites the occipital bone with the parietal bones of the skull.
Plagiocephaly is a condition characterized by an asymmetrical distortion
(flattening of one side) of the skull. It is a common finding at birth and
may be the result of brain malformation, a restrictive intrauterine
environment, or torticollis (a spasm or tightening of neck muscles).
SCAPHOCEPHALY applies to premature fusion of the sagittal
suture. The sagittal suture joins together the two parietal bones of
skull. Scaphocephaly is the most common of the craniostenoses and is
characterized by a long, narrow head.
TRIGONOCEPHALY is the premature fusion of the metopic suture
(part of the frontal suture which joins the two halves of the frontal bone
of the skull) in which a V-shaped abnormality occurs at the front of the
skull. It is characterized by the triangular prominence of the forehead
and closely set eyes.
Within the Federal Government, the National Institute of Neurological
Disorders and Stroke (NINDS), one of the National Institutes of Health
(NIH), has primary responsibility for conducting and supporting research
on normal and abnormal brain and nervous system development, including
congenital anomalies. The National Institute of Child Health and Human
Development, the National Institute of Mental Health, the National
Institute of Environmental Health Sciences, the National Institute of
Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse
also support research related to disorders of the developing nervous
system. Gaining basic knowledge about how the nervous system develops and
understanding the role of genetics in fetal development are major goals of
scientists studying congenital neurological disorders.
Scientists are rapidly learning how harmful insults at various stages
of pregnancy can lead to developmental disorders. For example, a critical
nutritional deficiency or exposure to an environmental insult during the
first month of pregnancy (when the neural tube is formed) can produce
neural tube defects such as anencephaly.
Scientists are also concentrating their efforts on understanding the
complex processes responsible for normal early development of the brain
and nervous system and how the disruption of any of these processes
results in congenital anomalies such as cephalic disorders. Recently, two
new genes have been discovered that are causes of lissencephaly and milder
neuronal migration disorders. Understanding how genes control brain cell
migration, proliferation, differentiation, and death, and how radiation,
drugs, toxins, infections, and other factors disrupt these processes will
aid in preventing many congenital neurological disorders.
Currently, researchers are examining the mechanisms involved in
neurulation - the process of forming the neural tube. These studies will
improve our understanding of this process and give insight into how the
process can go awry and cause devastating congenital disorders.
Investigators are also conducting a variety of genetic studies. One of
these studies concentrates on a specific form of holoprosencephaly with
the goal of finding the basic DNA defect responsible for the abnormal
development seen in this disorder. Researchers are also analyzing genes
and gene products necessary for human brain development to achieve a
better understanding of normal brain development in humans.
Other research projects currently under way include a study to evaluate
increased risk of neural tube defects and various other congenital
malformations in association with environmental and occupational exposure
to pesticides.
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For more information about disorders of the developing nervous system,
cephalic disorders, or birth defects in general, you may wish to
contact:
National Organization for Rare Disorders, Inc. (NORD)
55 Kenosia
Avenue
P.O. Box 1968
Danbury, CT 06813-1968
(203)
744-0100
(800) 999-6673 (voicemail only)
Fax: (203) 798-2291
http://www.rarediseases.org/
The Lissencephaly Network, Inc.
716 Autumn Ridge Lane
Fort Wayne,
Indiana 46804-6402
(219) 432-4310
http://www.lissencephaly.org/
The March of Dimes Birth Defects Foundation
1275 Mamaroneck
Avenue
White Plains, New York 10605
(914) 428-7100
(888) MODIMES
(663-4637)
http://www.modimes.org/
Association of Birth Defects Children
930 Woodcock Rd.
Orlando,
Florida 32803
(407) 245-7035
(800) 313-ABDC (2232)
http://www.birthdefects.org/
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