Aicardi syndrome
Encyclopedia
Aicardi syndrome is a rare genetic malformation syndrome
characterized by the partial or complete absence of a key structure in the brain called the corpus callosum
, the presence of retinal abnormalities, and seizures in the form of infantile spasms. Aicardi syndrome is theorized to be caused by a defect on the X chromosome
as it has thus far only been observed in girls or in boys with Klinefelter's syndrome
. Confirmation of this theory awaits the discovery of the gene
which causes Aicardi syndrome. Symptoms typically appear before a baby reaches about 5 months of age.
, a French neurologist. A review article by Dr. Aicardi (Aicardi J, Aicardi syndrome: old and new findings, Int Pediatr. 1998;14(1):5-8) describes the syndrome. Aicardi syndrome should not be confused with Aicardi-Goutières syndrome
, a distinct disorder.
Aicardi syndrome appears to be lethal in normal males who have only one X chromosome
(and a Y chromosome
). In other words, Aicardi syndrome appears to be inherited in an X-linked dominant
pattern due to a mutant gene on the X chromosome
that is lethal in XY males.
All cases of Aicardi syndrome are thought to be due to new mutations. No person with Aicardi syndrome is known to have transmitted the X-linked gene responsible for the syndrome to the next generation.
Other types of defects of the brain such as microcephaly
, polymicrogyria
, porencephalic cyst
s and enlarged cerebral ventricle
s due to hydrocephalus
are also common in Aicardi syndrome.
Additional complications sometimes seen with Aicardi syndrome include porencephalic cyst
s and hydrocephalus
, and gastro-intestinal problems. Treatment for prencephalic cysts and/or hydrocephalus is often via a shunt
or endoscopic fenestration of the cysts, though some require no treatment. Placement of a feeding tube
, fundoplication, and surgeries to correct hernias or other gastrointestinal structural problems are sometimes used to treat gastro-intestinal issues.
varies widely from case to case, depending on the severity of the symptoms. However, almost all people reported with Aicardi syndrome to date have experienced developmental delay of a significant degree, typically resulting in moderate to profound mental retardation
. The age range of the individuals reported with Aicardi syndrome is from birth to the mid 40s.
There is no cure for this syndrome.
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
characterized by the partial or complete absence of a key structure in the brain called the corpus callosum
Agenesis of the corpus callosum
Agenesis of the corpus callosum is a rare birth defect in which there is a complete or partial absence of the corpus callosum. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally,...
, the presence of retinal abnormalities, and seizures in the form of infantile spasms. Aicardi syndrome is theorized to be caused by a defect on the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
as it has thus far only been observed in girls or in boys with Klinefelter's syndrome
Klinefelter's syndrome
Klinefelter syndrome, 46/47, XXY, or XXY syndrome is a condition in which human males have an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome...
. Confirmation of this theory awaits the discovery of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
which causes Aicardi syndrome. Symptoms typically appear before a baby reaches about 5 months of age.
History
This disorder was first recognized as a distinct syndrome in 1965 by Jean AicardiJean Aicardi
Jean Aicardi is a French doctor.Aicardi syndrome and Aicardi-Goutieres syndrome are named after him.Aicardi syndrome only affects females, and in very rare cases, males with Klinefelter syndrome .-References:...
, a French neurologist. A review article by Dr. Aicardi (Aicardi J, Aicardi syndrome: old and new findings, Int Pediatr. 1998;14(1):5-8) describes the syndrome. Aicardi syndrome should not be confused with Aicardi-Goutières syndrome
Aicardi-Goutieres syndrome
Aicardi–Goutières syndrome is a rare genetic disorder. It is also known as Cree encephalitis and pseudo-TORCH syndrome, both of which were once considered separate disorders. It is a type of leukodystrophy and is usually fatal within the first few years...
, a distinct disorder.
Epidemiology
Worldwide prevalence of Aicardi Syndrome is estimated at several thousand, with approximately 900 cases reported in the United States.Genetics
Almost all reported cases of Aicardi syndrome have been in females. The few males that have been identified with Aicardi syndrome have proved to have 47 chromosomes including an XXY sex chromosome complement, a condition called Klinefelter syndrome.Aicardi syndrome appears to be lethal in normal males who have only one X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
(and a Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
). In other words, Aicardi syndrome appears to be inherited in an X-linked dominant
X-linked dominant
X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type...
pattern due to a mutant gene on the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
that is lethal in XY males.
All cases of Aicardi syndrome are thought to be due to new mutations. No person with Aicardi syndrome is known to have transmitted the X-linked gene responsible for the syndrome to the next generation.
Features
Children are most commonly identified with Aicardi syndrome before the age of five months. A significant number of girls are products of normal births and seem to be developing normally until around the age of three months, when they begin to have infantile spasms. The onset of infantile spasms at this age is due to closure of the final neural synapses in the brain, a stage of normal brain development.Diagnosis
Aicardi syndrome is typically characterized by the following triad of features - however, one of the "classic" features being missing does not preclude a diagnosis of Aicardi Syndrome, if other supporting features are present.- Partial or complete absence of the corpus callosumCorpus callosumThe 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...
in the brain (agenesis of the corpus callosumAgenesis of the corpus callosumAgenesis of the corpus callosum is a rare birth defect in which there is a complete or partial absence of the corpus callosum. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally,...
); - Eye abnormalities known as "lacunaLacunaLacuna may refer to:* Lacuna , a missing section of text* Lacuna , an extended silence in a piece of music* Lacuna , a lexical gap in a language* Lacuna , the lack of a law or legal source addressing a situation...
e" of the retina that are quite specific to this disorder; and - The development in infancy of seizures that are called infantile spasms.
Other types of defects of the brain such as microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
, polymicrogyria
Polymicrogyria
Polymicrogyria is a developmental malformation of the human brain characterized by an excessive number of small convolutions on the surface of the brain...
, porencephalic cyst
Porencephaly
Porencephaly is a type of cephalic disorder involving encephalomalacia. This 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...
s and enlarged cerebral ventricle
Ventricular system
The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.-Components:The system comprises four ventricles:* right and left lateral ventricles* third ventricle...
s due to 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,...
are also common in Aicardi syndrome.
Treatment
Treatment of Aicardi syndrome primarily involves management of seizures and early/continuing intervention programs for developmental delays.Additional complications sometimes seen with Aicardi syndrome include porencephalic cyst
Porencephaly
Porencephaly is a type of cephalic disorder involving encephalomalacia. This 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...
s and 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,...
, and gastro-intestinal problems. Treatment for prencephalic cysts and/or hydrocephalus is often via a shunt
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...
or endoscopic fenestration of the cysts, though some require no treatment. Placement of a feeding tube
Feeding tube
A feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by swallowing. The state of being fed by a feeding tube is called gavage, enteral feeding or tube feeding...
, fundoplication, and surgeries to correct hernias or other gastrointestinal structural problems are sometimes used to treat gastro-intestinal issues.
Prognosis
The prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
varies widely from case to case, depending on the severity of the symptoms. However, almost all people reported with Aicardi syndrome to date have experienced developmental delay of a significant degree, typically resulting in moderate to profound mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. The age range of the individuals reported with Aicardi syndrome is from birth to the mid 40s.
There is no cure for this syndrome.
External links
- GeneReviews/NCBI/NIH/UW entry on Aicardi Syndrome
- OMIM entries on Aicardi syndrome
- Phenotype and Management of Aicardi Syndrome: New Findings from a Survey of 69 Children
- Neurology India: Aicardi syndrome: A report of five Indian cases
- Aicardi Syndrome: Old and New Findings
- ninds.nih.gov
- UCSF Brain Development Research Program
- Baylor Department of Molecular and Human Genetics