Heterozygous FOXC1 mutation (M161K) associated with congenital glaucoma and aniridia in an infant and a milder phenotype in her mother.
OBJECTIVE
To report the genetic basis for congenital glaucoma with clinical aniridia in an infant and a milder phenotype in her mother.


METHODS
Prospective case series.


RESULTS
An infant girl with almost complete lack of iris tissue was referred and treated for congenital glaucoma. Although the presumed clinical diagnosis was aniridia (On-line Mendelian Inheritance in Man [OMIM] AN2, # 106210), PAX6 sequencing was normal. Examination of the infant's mother was significant for Axenfeld-Rieger malformation (ARM): prominent Schwabe line, subtle iris hypoplasia, iris stands bridging the angle, increased intraocular pressure, and glaucomatous optic nerve cupping. Both parents and the infant underwent diagnostic FOXC1 DNA sequencing. A heterozygous M161K FOXC1 mutation was found in the infant and her mother but not in the father, who had a normal ocular examination.


CONCLUSIONS
The spectrum of intrafamilial phenotypic variation associated with heterozygous FOXC1 mutation can be wide. FOXC1 mutation can be a cause of congenital glaucoma with clinical aniridia. Although such infants resemble the AN2 phenotype, the glaucoma of AN2 due to PAX6 mutation is typically secondary with onset several years after birth.
Khan
Arif O
AO
Pediatric Ophthalmology Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu <arif.khan@mssm.edu>
Aldahmesh
Mohammad A
MA
Al-Amri
Abdullah
A
D015783:Aniridia / Q000188:drug therapy / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005838:Genotype; D005901:Glaucoma / Q000151:congenital / Q000235:genetics*; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007498:Iris / Q000002:abnormalities*; D008297:Male; D009154:Mutation / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D010290:Parents; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics
D005136:Eye Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins