Neuroimaging aspects of Aicardi syndrome.
American Journal of Medical Genetics Part A. 2008; 146A:2871-2878.
Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G.
Summary: Abnormalities identified on magnetic resonance neuroimaging (MRI) studies were reviewed from 23 girls with Aicardi syndrome to better characterize the central nervous system abnormalities common to this condition. We found that all patients had complete or partial dysgenesis of the corpus callosum, cerebral asymmetry, and polymicrogyria (many small brain folds) that was more prominent in the front that in the back. Periventricular nodular heterotopias (mislocalized nodules of brain cells) were present in all patients as well. Intracranial cysts were seen in 95% of girls and cerebellar abnormalities were also seen in 95% of participants. The operculum was underdeveloped in nearly three-fourths of patients. The operculum is the back-most portion of the frontal lobe in the brain. A portion of the operculum plays an important role in speech, reading and writing. Tectal enlargement was noted as a new finding in Aicardi syndrome. This is a section of brain that is involved in hearing and vision.
Take home message: This study is important both because central nervous system abnormalities are the most prominent component of Aicardi syndrome and because this is the largest group of girls with Aicardi syndrome for which MRI findings have been reviewed by a single investigator. New finding included the presence of tectal (part of the midbrain that controls auditory and visual responses) enlargement, seen in nearly half the girl evaluated, and a greater frequency of girls with heterotopias (mislocalized nodules of brain cells) than previously reported.
Mutations in X linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia.
Nature Genetics. 2007; 39(7):836-838.
Wang X, Sutton VR, Peraza-Llanes J, Yu Z, Rosetta R, Kou Y, Eble TN, Patel A, Thaller C, Fang P, Van den Veyver I.
Summary: Using array comparative genomic hybridization (CGH) we identified a deletion (missing piece) on the X chromosome in two girls with Goltz syndrome, a disorder which like Aicardi syndrome is mostly seen in girls. Array CGH is a process used to compare the amount of DNA in an individual with a sample that is known to be normal. With this process we can determine if even a very small amount of DNA is extra or missing. Depending on their size, these areas of extra or missing DNA may contain one or several genes. In this study the portion of DNA that was missing in the two girls with Goltz syndrome was located on the X chromosome. Several genes located in the region were sequenced, or “read,” and we found mutations in a gene called PORCN. This gene is involved in secreting Wnt proteins. Much remains to be learned about Wnt proteins but they are known to play a very important role in development and function of many body parts and organs. Future plans include continued investigation of how mutations in PORCN affect the phenotype, or features, of people with Goltz syndrome. The lab also seeks to gain a better understanding of how mutations in PORCN affect the Wnt proteins.
Take home message: Using array CGH the Van den Veyver lab identified the genetic cause of Goltz syndrome, mutations in PORCN. The same methods are being applied in our studies to determine the cause of Aicardi syndrome. As with Aicardi syndrome, evidence had long suggested that Goltz syndrome was due to mutations on the X chromosome because it primarily occurs in girls. This work shows that this method can be successful for conditions that are similar to Aicardi syndrome.
Facial and phenotypic features of Aicardi syndrome: Infants to teenagers.
American Journal of Medical Genetics. 2005. 138A:254-258.
Sutton VR, Hopkins BJ, Eble TN, Gambhir N, Lewis RA, Van den Veyver IB.
Summary: Forty girls with Aicardi syndrome were examined and we found that more than half of the girls evaluated had certain notable facial features including prominent premaxilla (the upper jaw is positioned forward more than usual), the tip of the nose is upturned, the bridge of the nose has a smaller angle out from the face than usual, and thin eyebrows. Twenty-five percent of the girls that were examined had microphthalmia (small eyes). Skin lesions such as nevi (mole or birthmark), skin tags and hemangiomas (a benign reddish tumor that involves cells that would normally line blood vessels) were seen in 20% of the girls. Less frequently (7.5%) we observed minor hand abnormalities such as camptodactyly (bent finger), abnormal position of the thumb, and small fifth fingers.
Take home message: Prior to this study, no specific description of facial features common among girls with Aicardi syndrome had been reported. We suggested that these findings be used in the future to help doctors diagnosis Aicardi syndrome. Most often a diagnosis of Aicardi syndrome is made by an ophthalmologist because of the typical retinal lacunae that girls have. In particular, it is hoped that this description of additional features of Aicardi syndrome will help doctors determine the diagnosis for girls who do not have these typical eye findings. Also, due to the skin and vascular changes that we noted in a significant proportion of girls with Aicardi syndrome we recommend regular surveillance of the skin.
