Aicardi Syndrome

Clinical Characteristics
Ocular Features: 

A variety of chorioretinal lesions have been described in Aicardi syndrome including lacunae ('holes') in 88%, and choroid plexus papillomas which are considered specific and characteristic.  These tend to be more common in the posterior pole. They are stable and do not enlarge.  They can usually be distinguished from post-infection scars by the absence of pigmentation.  A bull's eye maculopathy may be present.  Optic nerve colobomas (in 42%) and hypoplasia have been reported.   At least 61% of eyes have some optic nerve abnormalities.  Presumed microphthalmia has been noted in 25% of patients. A minority of patients have a persistent pupillary membrane.  Sparse lateral eyebrows have also been reported with .

There is evidence that the primary molecular defect involves Bruch's membrane resulting in damage to the RPE.

Congenital glaucoma has been diagnosed in several patients.

Systemic Features: 

Patients with Aicardi syndrome are considered to have a characteristic facial phenotype with a prominent premaxilla, upturned nasal tip, and decreased angle of the nasal bridge.  Several patients have been reported with vertebral anomalies as well as cleft lip and palate.  The most severe symptoms including infantile spasms, developmental delay, and seizures are the result of a generalized neuronal migration disorder evident on MRI as polymicrogyria, periventricular heterotopia, and various malformations of the corpus callosum.  The latter structure is absent in 72% of patients.  Intracranial cysts and cerebellar dysplasia have been reported in 95% of patients.  MRI of the brain often shows asymmetry and unilateral microphthalmia is often present on the side of the more severe brain lesions.  Most individuals have some intellectual disabilities and do not live beyond childhood.

Genetics

Since virtually all reported cases have been female this is considered to be a dominant X-linked disorder with lethality in hemizygous males.  The presumed locus is at Xp22 although no specific gene mutation has been identified. Interestingly, several affected XXY (Klinefelter syndrome) males have been reported which is consistent with the most likely mode of inheritance.  It has been proposed that the majority of cases results from new mutations since familial cases are exceedingly rare.

Aicard-Goutieres syndromes are separate disorders.

Treatment
Treatment Options: 

No treatment is available for the syndrome.  However, specific features such as congenital glaucoma may require treatment.

References
Article Title: 

Laterality of brain and ocular lesions in aicardi syndrome

Cabrera MT, Winn BJ, Porco T, Strominger Z, Barkovich AJ, Hoyt CS, Wakahiro M, Sherr EH. Laterality of brain and ocular lesions in aicardi syndrome. Pediatr Neurol. 2011 Sep;45(3):149-54. PubMed PMID: 21824560.

PubMed ID: 
21824560

Neuroimaging aspects of Aicardi syndrome

Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G. Neuroimaging aspects of Aicardi syndrome. Am J Med Genet A. 2008 Nov 15;146A(22):2871-8.

PubMed ID: 
18925666

References

Tuft M, Ostby Y, Nakken KO, Lund C. Aicardi syndrome and cognitive abilities: A report of five cases. Epilepsy Behav. 2017 Jun 19;73:161-165.

PubMedID: 28641168

Henrickson M, Wang H. Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation. Clin Rheumatol. 2017 Mar 13. doi: 10.1007/s10067-017-3600-2. [Epub ahead of print] Review.

PubMedID: 28289923

Savige J, Wang Y, Crawford A, Smith J, Symons A, Mack H, Nicholls K, Wilson D, Colville D. Bull's eye and pigment maculopathy are further retinal manifestations of an abnormal Bruch's membrane in Alport syndrome. Ophthalmic Genet. 2016 Aug 2:1-7.

PubMedID: 27485810

Fruhman G, Eble TN, Gambhir N, Sutton VR, Van den Veyver IB, Lewis RA. Ophthalmologic findings in Aicardi syndrome. J AAPOS. 2012 Jun;16(3):238-41.

PubMedID: 22681940

Cabrera MT, Winn BJ, Porco T, Strominger Z, Barkovich AJ, Hoyt CS, Wakahiro M, Sherr EH. Laterality of brain and ocular lesions in aicardi syndrome. Pediatr Neurol. 2011 Sep;45(3):149-54. PubMed PMID: 21824560.

PubMedID: 21824560

Chen TH. Increasing recognition of cases with male Aicardi syndrome. J Child Neurol. 2010 Jan;25(1):129.

PubMedID: 20032521

Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G. Neuroimaging aspects of Aicardi syndrome. Am J Med Genet A. 2008 Nov 15;146A(22):2871-8.

PubMedID: 18925666

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.

PubMedID: 16158440

Crow YJ, Massey RF, Innes JR, Pairaudeau PW, Rowland Hill CA, Woods CG, Ali M, Livingston JH, Lebon P, Nischall K, McEntagart M, Hindocha N, Winter RM. Congenital glaucoma and brain stem atrophy as features of Aicardi-Goutieres syndrome. Am J Med Genet A. 2004 Sep 1;129A(3):303-7.

PubMedID: 15326633

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.

PubMedID: 2773986