content:aicardi_syndrome

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.

  • 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[1]. 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[2]. EEG features include asynchronous multifocal epileptiform abnormalities with burst suppression and dissociation between the two hemispheres[3].

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[4]).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.

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[5] hand abnormalities including camptodactyly, proximal placement of the thumb, and hypoplasia of the fifth finger[6][7].

Sutton et al. (2005) proposed the following modified diagnostic criteria[7]:

  • 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
  • Nearly all reported cases of Aicardi syndrome are sporadic and in females and believed to result from new gene mutations
  • Aicardi syndrome is classified as an X-linked dominant condition
    Credit:U.S National Library of Medicine

    .

  • mutation in gene TEAD1 was the first genetic mutation reported to be associated with Aicardi syndrome[8]. TEAD1 mutations has also been shown to be present in males[8].

Neuroimaging

Abnormalities identified on MRI are characteristically[9]

  • 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[10]

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[11]. Further 7 patients were described in 1969[5] and the name “Aicardi syndrome” was established in 1972, by Dennis and Bower[12].


1. a Aicardi Jean. Aicardi syndrome. Brain Dev. 2005 Apr;27(3):164-71. PMID : 15737696
2. a Glasmacher Margaret A K, Sutton V Reid, Hopkins Bobbi, Eble Tanya, Lewis Richard A, Park Parsons Denise, Van den Veyver Ignatia B. Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children. J Child Neurol. 2007 Feb;22(2):176-84. PMID : 17621479
3. a Palmér L, Zetterlund B, Hård A-L, Steneryd K, Kyllerman M. Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002. Neuropediatrics. 2006 Jun;37(3):154-8. PMID : 16967367
4. a Shah Parag K, Narendran V, Kalpana N. Aicardi syndrome: the importance of an ophthalmologist in its diagnosis. Indian J Ophthalmol. 2009 May-Jun;57(3):234-6. PMID : 19384023
5. a, b Aicardi J, Chevrie J J, Rousselie F. [Spasma-in-flexion syndrome, callosal agenesis, chorioretinal abnormalities]. Arch Fr Pediatr. 1969;26(10):1103-20. PMID : 4314028
6. a Donnenfeld A E, Packer R J, Zackai E H, Chee C M, Sellinger B, Emanuel B S. Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome. Am J Med Genet. 1989 Apr;32(4):461-7. PMID : 2773986
7. a, b Sutton V Reid, Hopkins Bobbi J, Eble Tanya N, Gambhir Nikki, Lewis Richard A, Van den Veyver Ignatia B. Facial and physical features of Aicardi syndrome: infants to teenagers. Am J Med Genet A. 2005 Oct 15;138A(3):254-8. PMID : 16158440
8. a, b Schrauwen Isabelle, Szelinger Szabolcs, Siniard Ashley L, Corneveaux Jason J, Kurdoglu Ahmet, Richholt Ryan, De Both Matt, Malenica Ivana, Swaminathan Shanker, Rangasamy Sampathkumar, Kulkarni Neil, Bernes Saunder, Buchhalter Jeffrey, Ramsey Keri, Craig David W, Narayanan Vinodh, Huentelman Matthew J. A De Novo Mutation in TEAD1 Causes Non-X-Linked Aicardi Syndrome. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3896-904. PMID : 26091538
9. a Hopkins Bobbi, Sutton V Reid, Lewis Richard Alan, Van den Veyver Ignatia, Clark Gary. Neuroimaging aspects of Aicardi syndrome. Am J Med Genet A. 2008 Nov 15;146A(22):2871-8. PMID : 18925666
10. a RESERVED, I. (2020). Orphanet: Aicardi syndrome. [online] Orpha.net. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=50 [Accessed 13 Feb. 2020].
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 Dennis J, Bower B D. The Aicardi syndrome. Dev Med Child Neurol. 1972 Jun;14(3):382-90. PMID : 4624502
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