Abstract
Purpose: :
:To study the clinical phenotype and genetic causes of a cohort of 26 consecutive patients with congenital micro/anophthalmia (MA) seen at a pediatric eye clinic.
Methods: :
Patients where assessed by a pediatric ophthalmologist and an ophthalmic geneticist to define ocular and extra ocular dysmorphogy phenotype. Brain MRI , karyotype telomeric screen and CGH array were done on some patients.Gene mutation analysis performed by pcr and sequencing are ongoing for several genes including PITX3,OTX2,SOX2,BCOR,ND,NHS,LRP5
Results: :
The cohort was divided into primary and secondary MA (post infectious, post–surgical, post retinal detachment or post–phthisis) The cohort is comprised of 26 patients 2 months to 28 years (average 6 years), 7 (27%) females and 19 (63%)males.20 patients(77%) had primary MA and 6 (23%)had secondary MA. Blindness affected 12/20 (60%) patients with primary MA versus 2/6 (33%) with secondary MA. Patients were classified as ocular alone in 4/20 ( 25%) of primary MA versus 6/6 (100%) with secondary MA or syndromic in 75% of primary MA versus none of the secondary MA patients. MA was unilateral in 2/20 (10%) of primary MA and in 3/6 (50%) of secondary MA patients. 2/20 patients with primary MA died and none of the 6 secondary MA.
Associated findings in syndromic cases included brain, neurologic,pituitary,mental retardation ,autism,dental,cleft palate,cardiac, pulmonary,diaphragmatic,genito–urinary, limb,or bone disorder.
Genetic evaluation showed 5 familial case (4 autosomal dominant and one possibly autosomal recessive). One patient had a ring chromosome 18; 2 patients had Norrie disease(ND), one had Nance Horan (cataract dental) syndrome (NHS)
Conclusions: :
Primary congenital MA is a moderately severe bilateral(90%)sometimes familial (15%)syndromic (75%)rarely lethal (10%)disorder affecting mostly males(63%),causing blindness(60%) associated with multiple malformations. The excess of males and the paucity of X linked genes involved seems to imply that most X linked genes involved with MA are yet unknown
Keywords: genetics • clinical (human) or epidemiologic studies: natural history • development