Aicardi syndrome
A rare neurodevelopmental disorder characterized by the classic triad of agenesis of the corpus callosum (total or partial), central chorioretinal lacunae and infantile spasms that affects almost exclusively females & rarely in 47 XXY males. However Aicardi syndrome is now recognized as a more complex, pleiotropic disorder with an expanded spectrum of phenotypical features.
Clinical features
Agenesis of the corpus callosum
Infantile spasms
Chorioretinal lacunae
Microcephaly, heterotopias
polymicrogyria
Cerebellar dysgenesis
Microphthalmia , coloboma
Costovertebral defects
Facial asymmetry
Intellectual disability
developmental delay
hypotonia
Focal seizures
Seizures
Infantile spasms are the most characteristic seizure type in Aicardi syndrome. Most seizures appear early, at 3–4 months of age, and are often asymmetric or even unilateral. With increasing age, the seizure pattern evolves and focal seizures become more frequent. EEG features include asynchronous multifocal epileptiform abnormalities with burst suppression and dissociation between the two hemispheres.
Chorioretinal lacunae
Retcam photo of right eye shows optic disc coloboma (black arrow) and dome shaped loci of pale areas with sharp borders nasal to the optic disc suggestive of chorio retinal lacunae (white arrows).
Central Chorioretinal lacunae (CRL) represent a defect of the pigment epithelium and choroid. CRL are pathognomonic for Aicardi syndrome and are seen in all patients (see figure).They are well-defined, multifocal pale areas with minimally pigmented borders, and are usually found in the peripapillary area of the posterior pole. They do not change or evolve over time. CRL do not affect vision unless the central foveal area is involved.
Optic nerve anomalies are present in the majority of affected individuals, with coloboma being the most common. Other abnormalities include asymmetric microphthalmia, morning glory discs, abnormal retinal vessels and cysts and often result in significant visual impairment.
Dysmorphology
Aicardi syndrome is associated with distinctive facial features including prominent premaxilla, upturned nasal tip, decreased angle of the nasal bridge, and sparse lateral eyebrows.
Other abnormalities reported include hemivertebrae, block vertebrae, fused vertebrae, and missing, malformed or fused ribs hand abnormalities including camptodactyly, proximal placement of the thumb, and hypoplasia of the fifth finger.
Diagnostic criteria
Sutton et al. (2005) proposed the following modified diagnostic criteria:
The presence of all three classical features (classic triad) is diagnostic for Aicardi syndrome
The presence of two classical features in addition to at least two major or supporting features is strongly suggestive of a diagnosis of Aicardi syndrome
Genetics
Neuroimaging
Abnormalities identified on MRI are characteristically
polymicrogyria that was predominantly frontal and perisylvian and often associated with underopercularization
Periventricular nodular heterotopias
single or multiple intracranial cysts
Cerebellar abnormalities
tectal enlargement
Differential Diagnosis
Treatment
seizure management. Seizures are often refractory
physical, occupational, speech therapy
vision
management of vertebral abnormalities including scoliosis
Prognosis
majority of children are unable to sit independently, walk or talk
The 5-, 10- and 20-year survival rates are 90%, 80% and 50%, respectively
History
In 1965 French pediatric neurologist and epileptologist Jean Aicardi described 8 children with infantile spasm-in-flexion, total or partial agenesis of the corpus callosum, and variable ocular abnormalities. Further 7 patients were described in 1969 and the name “Aicardi syndrome” was established in 1972, by Dennis and Bower.
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References
2.
a
Glasmacher MAK, Sutton VR, Hopkins B, Eble T, Lewis RA, Park Parsons D, Van den Veyver IB. Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children. J Child Neurol. 2007 Feb;22(2):176-84. doi: 10.1177/0883073807300298.
[PMID: 17621479] [DOI: 10.1177/0883073807300298]
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a
Palmér L, Zetterlund B, Hård A, Steneryd K, Kyllerman M. Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002. Neuropediatrics. 2006 Jun;37(3):154-8. doi: 10.1055/s-2006-924486.
[PMID: 16967367] [DOI: 10.1055/s-2006-924486]
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a
Aicardi J, Chevrie JJ, Rousselie F. [Spasma-in-flexion syndrome, callosal agenesis, chorioretinal abnormalities]. Arch Fr Pediatr. 1969;26(10):1103-20.
[PMID: 4314028]
6.
a
Donnenfeld AE, Packer RJ, Zackai EH, Chee CM, Sellinger B, Emanuel BS. Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome. Am J Med Genet. 1989 Apr;32(4):461-7. doi: 10.1002/ajmg.1320320405.
[PMID: 2773986] [DOI: 10.1002/ajmg.1320320405]
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a,
b
Sutton VR, Hopkins BJ, Eble TN, Gambhir N, Lewis RA, Van den Veyver IB. Facial and physical features of Aicardi syndrome: infants to teenagers. Am J Med Genet A. 2005 Oct 15;138A(3):254-8. doi: 10.1002/ajmg.a.30963.
[PMID: 16158440] [DOI: 10.1002/ajmg.a.30963]
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Schrauwen I, Szelinger S, Siniard AL, Corneveaux JJ, Kurdoglu A, Richholt R, De Both M, Malenica I, Swaminathan S, Rangasamy S, Kulkarni N, Bernes S, Buchhalter J, Ramsey K, Craig DW, Narayanan V, Huentelman MJ. A De Novo Mutation in TEAD1 Causes Non-X-Linked Aicardi Syndrome. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3896-904. doi: 10.1167/iovs.14-16261.
[PMID: 26091538] [DOI: 10.1167/iovs.14-16261]
11.
a
Aicardi J, Lefebvre J, Lerique-Koechlin A. A new syndrome: spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 1965;19:609-610
12.
a
Aicardi J, Chevrie JJ, Rousselie F. [Spasma-in-flexion syndrome, callosal agenesis, chorioretinal abnormalities]. Arch Fr Pediatr. 1969;26(10):1103-20.
[PMID: 4314028]