chorioretinal lacunae

Orofaciodigital Syndrome IX

Clinical Characteristics
Ocular Features: 

Multiple forms of orofaciodigital syndrome are recognized but this one (type IX, originally reported as VIII) is of ophthalmological interest because of the retinal anomalies.  Gurrieri’s original report calls these “retinochoroideal lacunae of colobomatous origin” similar to those found in Aicardi syndrome (304050).  These were further described as hypopigmented and atrophic appearing.  Synophyrs and hypertelorism have been noted and the ears may be low-set.

Systemic Features: 

Facial, oral, digital, psychomotor delays, and skeletal anomalies are major systemic features of OFD IX.  The oral manifestations include a high arched palate, cleft lip (sometimes subtle), bifid tongue, hemartomas on the tongue, abnormal tongue frenulation, and dental anomalies (supernumerary teeth).  Digital anomalies consist of mild syndactyly and occasionally polydactyly, brachydactyly, and bifid large toes.  Some patients have short stature.  Psychomotor delay is common and some patients have been described as mentally retarded.

Genetics

This is most likely an autosomal recessive condition since multiple sibs of both sexes have been identified.  Nothing is known of the locus or specific mutation.

Gurrieri’s name is attached to another syndrome (Gurrieri syndrome [601187]) with entirely different oculoskeletal features.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Specific malformations may need correction but there is no treatment for the overall disease.

References
Article Title: 

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.

Pedigree: 
X-linked dominant, father affected
X-linked dominant, mother affected
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
Subscribe to RSS - chorioretinal lacunae