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(Summaries by Tanya Eble,

New incidence, prevalence, and survival of Aicardi syndrome from 408 cases.
Journal of Child Neurology. 2008; 23(5):531-535.
Kroner BL, Preiss LR, Ardini M, Gaillard WD.

Summary: 408 international cases of Aicardi syndrome were compiled with the ages ranging from 1 month to 42 years at the time of data collection. In the United States 1 in 105,000 babies are born with Aicardi syndrome. At the time of publication 853 individuals with Aicardi syndrome were living in the United States. Worldwide it is estimated that there are several thousand people with Aicardi syndrome. Information was collected regarding forty-five people with Aicardi syndrome who had died and the most deaths were found to occur by age 16y. The average age at death was 8.8 years. (range of 1 month – 33 years). Based on data from 273 people with Aicardi syndrome in the United States, the chance of surviving until 27 years was found to be 62%.

Take home message: The life expectancy for Aicardi syndrome may be greater than previously expected with a reported 0.62 probability of survival to 27 years. The authors raise concerns that people with less typical Aicardi syndrome are not being diagnosed and suggest that life expectancy for individuals with Aicardi syndrome may be underestimated because the populations most often studied are those more typically or severely affected.


Aicardi syndrome in monozygotic twins.
Ophthalmic Genetics. 2008; 29:87-88.
Pons ME, Garcia CA.

Summary: In this paper, identical twin girls are reported as both being diagnosed with Aicardi syndrome. The girls were born prematurely at 27 weeks of pregnancy. A typical pregnancy lasts 40 weeks. Baby A was found to have chorioretinal lacunae, partial agenesis of the corpus callosum, large ventricles (spaces in the brain), and cortical atrophy (the outer portion of the brain is decreased in size). She began having seizures at 3 months. Baby B also had lacunae, partial agenesis of the corpus callosum, large ventricles, and additional brain abnormalities. She began having seizures at 6 months. The girls have three half-sisters and one half-brother through their father. There are no half-siblings through their mother. No other family members have Aicardi syndrome. The authors suggest that both girls are affected because there was a genetic change (mutation) in a very early stage of development of the babies, before the fertilized egg separated to become two babies. They cannot completely rule out the possibility that a mutation is present in the eggs or sperm in one of the twins’ parents. There are two previous cases of Aicardi syndrome and identical twins. In those two previous cases only one of each twin pair had Aicardi syndrome. The other twin was reportedly normal.

Take home message: This is the first report of identical twins who both have Aicardi syndrome. It supports the theory that Aicardi syndrome is genetic but sporadic resulting from a de novo mutation, meaning a mutation that is new in the individual, not inherited.


Choroid plexus papilloma expansion over 7 years in Aicardi syndrome.
Journal of Child Neurology. 2007; 22(4):484-487.
Frye RE, Polling JS, Ma LCK.

Summary: This is a case report of a 7-year-old girl with relatively mild Aicardi syndrome. The child had an MRI and was found to have a choroid plexus papilloma at 2 months of age. A choroid plexus papilloma is a rare benign slow-growing tumor that is found in the choroid plexus, which is the area of the brain where the cerebrospinal fluid is produced. Over the next 7 years the tumor grew without causing noticeable symptoms. Following removal of the tumor no changes in behavior or development were observed. She continued to have mild developmental delays, sleeping difficulties, impulsivity and behavioral outbursts. According to the authors there are 13 other reports of choroid plexus papillomas in children with Aicardi syndrome.

Take home message: Follow-up imaging is recommended if a child is found to have this tumor because choroid plexus papillomas can continue to grow over time. There may be no obvious symptoms if a child has a choroid plexus papilloma or if it enlarges. Management, including the need for surgical removal, is to be determined on an individual case basis. The tumor was removed in this case because of its growth and because the child occasionally complained of headaches. Its removal however did not improve the child’s development, sleep or behavior.


Phenotype and management of Aicardi syndrome: New findings from a survey of 69 children.
Journal of Child Neurology. 2007; 22(2):176-184.
Glasmacher MAK, Sutton VR, Hopkins B, Eble T, Lewis RA, Parsons DP, Van den Veyver I.

Summary:
Aicardi syndrome is a rare neurodevelopmental disorder characterized by agenesis of the corpus callosum, other developmental brain abnormalities, chorioretinal lacunae, and severe seizures. Current clinical knowledge is derived from small series that focus on these major defects. The authors performed a health survey on a large number of affected children to expand this knowledge and to uncover previously unrecognized features of Aicardi syndrome. Responses received from caregivers of 69 children with Aicardi syndrome met inclusion criteria for data analysis. Ages ranged from 5 months to 32 years (mean, 88 months). All subjects were girls, except for 1 boy with a 47,XXY karyotype. The authors found that the growth rate in Aicardi syndrome slows at age 10 years to below the 5th percentile and that weight gain slows at age 7 years to below the 25th percentile. The median age of survival was estimated at 18.5 (±4) years, more favorable than previously reported. The most common complication aside from seizures was gastrointestinal dysfunction, present in >90%. The results from this survey contribute new information on Aicardi syndrome that will benefit clinical management, and collected data will benefit phenotype-driven research toward its underlying cause.

A link to additional results is available here.


Intractable reflex audiogenic seizures in Aicardi syndrome.
Brain & Development. 2007; 29:243-246.
Grosso S, Farnetani MA, Bernardoni E, Morgese G, Balestri P.

Summary: This is a report of a single patient with Aicardi syndrome, an 18-year-old girl, who has reflex audiogenic seizures. There are seizures triggered by a sound such as musical pitch. In this case the girl has seizures specifically when she hears the starting tune of a particular television news show. The diagnosis of Aicardi syndrome was supported by the presence of retinal lacunae and partial agenesis of the corpus callosum in the presence of additional typical neurological features.

Take home message: The authors believe reflex audiogenic seizures should be included in the spectrum of features of girls with Aicardi syndrome.


Aicardi syndrome with favorable outcome: Case report and review.
Brain and Development. 2007; 29:443-446.
Grosso S, Lasorella G, Russo A, Galluzzi P, Morgese G, Balestri P.

Summary: The authors give a report of a 9-year-old girl with Aicardi syndrome who is less severely affected than we typically expect. She has hypoplasia of the corpus callosum, polymicrogyria, heterotopias, chorioretinal lacunae, and seizures which began at age four. Notably, her cognitive function and development is normal. In their review of current literature the authors highlight some variations in features from the classic triad among people with Aicardi syndrome. Grosso and colleagues point out that infantile spasms were absent in 5 out of 156 people with Aicardi syndrome, that in six of 186 individuals the corpus callosum was normal and that there are two reports of girls with Aicardi syndrome who do not have lacunae.

Take home message: The authors comment that their findings contradict a previous hypothesis that having fewer ocular abnormalities is associated with a better developmental outcome because their patient had bilateral chorioretinal lacunae and normal development. Overall the authors assert that it should not be assumed that the prognosis will be poor and that learning diasabilities will be present for all people with Aicardi syndrome. They conclude that the features of Aicardi syndrome should be expanded to include milder cases with less or no learning disability.


Aicardi syndrome: Follow-up investigation of Swedish children born in 1975-2002.
Neuropediatrics. 2007;38:188-192.
Palmer L, Zetterlund B, Hard AL, Steneryd K, Kyllerman M.

Summary: This is a follow-up study of a previous study published in 2006 (see summary below). The data is again drawn from a nation-wide survey of girls with Aicardi syndrome in Sweden. The surveys were completed by physicians. Fourteen of the girls evaluated in the initial study were re-examined by one of the authors of this study. The girls range from age 1-27y. All but one of the girls had severe mental retardation. Visual function ranged from normal to severely impaired. One girl had mild mental retardation and was seizure free. As of March 2006 twelve of the initial patients were still living with a median age of 13.5 years. The six girls that died had all belonged to the most disabled group and had very poorly controlled epilepsy. Two of these girls had died from malignant brain tumors, two from infection, one from general deterioration and heart failure, and one was sudden with no specific cause listed. Of the fourteen girls who were re-examined, one was seizure free following surgery, 13 had drug resistant seizures, and two were on ketogenic diet. Most of the families involved in the study reported epilepsy as their main problem. The frequency of seizures ranged from 1 per week to 10 per day and as with their previous study, Palmer et al reported a variety of seizure types. It was found that EEG abnormalities changed but did not normalize over time. Hypsarrhythmia (abnormal high amplitude waves and a background of irregular spikes on EEG), a common finding in girls with Aicardi syndrome, was not seen in all girls. There have not been previous reports of change in lacunae but in this study one of the girls had lacunar changes that disappeared. The same girl lost pigment around the optic disc. Five of nine (55%) girls evaluated had vertebral abnormalities. Nine of the fourteen girls had scoliosis.

Take home message: The authors agreed with previous studies that the prognosis for girls with Aicardi syndrome is generally very poor but acknowledge that milder cases do exist. All but one of the girls in this study had severe mental retardation, lacked the ability to walk unsupported, and had not acquired effective speech. Palmer and colleagues associated the onset of seizures with arrest and in some cases deterioration of development. This study did not find any association between physical features and severity of developmental delays.


Screening of subtle copy number changes in Aicardi syndrome patients with a high resolution X chromosome array-CGH.
European Journal of Medical Genetics. 2007; 50:386-391.
Yilmaz S, Fomtaine H, Brochet K, Gregoire M, Devignes M, Schaff J, Philippe C, Nemos C, McGregor JL, Jonveaux P.

Summary: The investigators used array based comparative genomic hybridization (array-CGH) to look for small deletions or duplications on the X chromosome of 18 girls with Aicardi syndrome. Array CGH is a process that compares the DNA from an individual with a DNA sample that is known to be normal. If we see more copies of genetic instructions in the patient’s sample then we know there is a duplication in that area of the DNA. Likewise if there are fewer copies than expected then we know there is a duplication. Because girls have two X chromosomes we would expect to see 2 copies at each location along the X chromosome. Not all changes in copy number however are associated with a disease. A polymorphism is a genetic change that is found in at least 1% of the general population and has not been found to cause a disease. The authors found several polymorphisms but no copy number changes that are likely to cause Aicardi syndrome. Particular attention was paid to the FLNA gene which encodes a substance called fillamin A. Mutations in filamin A have been found to result in periventricular heterotopias (abnormal migration of neurons) and in at least four specific X-linked disorders leading to a broad spectrum of neurological conditions. In this study sequencing of FLNA did not find mutations in any of the patients.

Take home message: The investigators did not find copy number changes (deletions or duplications) on the X chromosome that are likely to cause Aicardi syndrome. This does not mean that it is unlikely that a change on the X chromosome causes Aicardi syndrome. It may indicate that the current techniques are not sensitive enough to find it and further studies are needed. Specifically, samples from more people with Aicardi syndrome should be evaluated and we could study the X chromosome using an improved array with greater resolution. Greater resolution would mean looking at more locations along the X chromosome so that the space between each location is smaller.