# 120430

COLOBOMA OF OPTIC NERVE


Other entities represented in this entry:

OPTIC NERVE HEAD PITS, BILATERAL CONGENITAL, INCLUDED
MORNING GLORY DISC ANOMALY, INCLUDED

Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
11p13 ?Morning glory disc anomaly 120430 AD 3 PAX6 607108
11p13 ?Coloboma of optic nerve 120430 AD 3 PAX6 607108
Clinical Synopsis
 

Eyes
- Bilateral coloboma of optic nerve
- Retinal detachment
Inheritance
- Autosomal dominant
- ? same as 120200

TEXT

A number sign (#) is used with this entry because of evidence that coloboma of the optic nerve and morning glory disc anomaly are each caused by mutation in the PAX6 gene (607108). One such patient has been reported for each of the phenotypes.


Clinical Features

Congenital coloboma of the optic nerve is often associated with serious detachment of the macula. Savell and Cook (1976) observed 15 affected persons in 1 kindred. In 21 of the 30 eyes, present or past detachment of the retina was found. The coloboma was bilateral in all. It appeared as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disc. A variable amount of glial tissue was present in the coloboma. No male-to-male transmission was observed. It is not certain that this entity is separate from that discussed in 120200.

Jonas and Freisler (1997) used the designation 'bilateral congenital optic nerve pits' for this disorder, which they observed in 2 otherwise healthy female monozygotic sibs aged 15 years. In both twins, visual acuity was worse in the eye with the larger optic nerve head. The parents were ophthalmologically unremarkable; there were no other sibs. Retinal detachment extending from the optic disc to the ora serrata in the temporal upper quadrant developed in 1 eye.

Hornby et al. (2000) correlated visual function with clinical features and biometric findings in the eyes of children with coloboma. Of the 196 eyes with colobomatous malformations, 11 had microphthalmos with cyst (251505), and 185 eyes had coloboma (associated with microcornea in 155 eyes and with normal corneal diameter in 30 eyes). The visual prognosis depended on the phenotype of the more normal eye. Microphthalmos with cyst had the worst prognosis (all worse than 20/400). Microcornea with microphthalmos had a worse prognosis than microcornea without microphthalmos. For microcornea with microphthalmos, 67% saw worse than 20/400. Of the children with microcornea without microphthalmos, 76% saw better than 20/400. Simple coloboma (without microcornea or microphthalmos) had the best visual prognosis: only 7% saw 20/400 or worse. A corneal diameter of less than 6 mm had a poor visual prognosis, whereas a corneal diameter of more than 10 mm had a good prognosis.


Molecular Genetics

In a 5-year-old girl with bilateral morning glory disc anomaly and in a 1-year-old boy with iris anomaly, large coloboma of the optic nerve, retina, and choroid (120200), a remnant of hyaloid vessel proliferation (persistent hyperplastic primary vitreous; see 257910) bilaterally, and growth and mental retardation, Azuma et al. (2003) identified missense mutations in the PAX6 gene (607108.0017 and 607108.0019, respectively).


REFERENCES

  1. Azuma, N., Yamaguchi, Y., Handa, H., Tadokoro, K., Asaka, A., Kawase, E., Yamada, M. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am. J. Hum. Genet. 72: 1565-1570, 2003. [PubMed: 12721955, images, related citations] [Full Text]

  2. Hornby, S. J., Adolph, S., Gilbert, C. E., Dandona, L., Foster, A. Visual acuity in children with coloboma: clinical features and a new phenotype classification system. Ophthalmology 107: 511-520, 2000. [PubMed: 10711890, related citations] [Full Text]

  3. Jonas, J. B., Freisler, K. A. Bilateral congenital optic nerve head pits in monozygotic siblings. Am. J. Ophthal. 124: 844-846, 1997. [PubMed: 9402835, related citations] [Full Text]

  4. Savell, J., Cook, J. R. Optic nerve colobomas of autosomal-dominant heredity. Arch. Ophthal. 94: 395-400, 1976. [PubMed: 945057, related citations] [Full Text]


Marla J. F. O'Neill - updated : 8/15/2014
Marla J. F. O'Neill - updated : 8/29/2006
Victor A. McKusick - updated : 5/28/2003
Jane Kelly - updated : 11/21/2000
Victor A. McKusick - updated : 3/27/1998
Creation Date:
Victor A. McKusick : 6/4/1986
carol : 08/18/2014
mcolton : 8/15/2014
carol : 8/30/2006
carol : 8/29/2006
terry : 3/11/2005
mgross : 5/28/2003
mcapotos : 11/21/2000
psherman : 3/27/1998
dholmes : 3/5/1998
mimadm : 6/25/1994
supermim : 3/16/1992
supermim : 3/20/1990
ddp : 10/26/1989
marie : 3/25/1988
marie : 12/15/1986

# 120430

COLOBOMA OF OPTIC NERVE


Other entities represented in this entry:

OPTIC NERVE HEAD PITS, BILATERAL CONGENITAL, INCLUDED
MORNING GLORY DISC ANOMALY, INCLUDED

SNOMEDCT: 44295002;   ICD10CM: H47.31, H47.319, Q14.2;   ICD9CM: 377.23;   ORPHA: 35737;   DO: 11975;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
11p13 ?Morning glory disc anomaly 120430 Autosomal dominant 3 PAX6 607108
11p13 ?Coloboma of optic nerve 120430 Autosomal dominant 3 PAX6 607108

TEXT

A number sign (#) is used with this entry because of evidence that coloboma of the optic nerve and morning glory disc anomaly are each caused by mutation in the PAX6 gene (607108). One such patient has been reported for each of the phenotypes.


Clinical Features

Congenital coloboma of the optic nerve is often associated with serious detachment of the macula. Savell and Cook (1976) observed 15 affected persons in 1 kindred. In 21 of the 30 eyes, present or past detachment of the retina was found. The coloboma was bilateral in all. It appeared as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disc. A variable amount of glial tissue was present in the coloboma. No male-to-male transmission was observed. It is not certain that this entity is separate from that discussed in 120200.

Jonas and Freisler (1997) used the designation 'bilateral congenital optic nerve pits' for this disorder, which they observed in 2 otherwise healthy female monozygotic sibs aged 15 years. In both twins, visual acuity was worse in the eye with the larger optic nerve head. The parents were ophthalmologically unremarkable; there were no other sibs. Retinal detachment extending from the optic disc to the ora serrata in the temporal upper quadrant developed in 1 eye.

Hornby et al. (2000) correlated visual function with clinical features and biometric findings in the eyes of children with coloboma. Of the 196 eyes with colobomatous malformations, 11 had microphthalmos with cyst (251505), and 185 eyes had coloboma (associated with microcornea in 155 eyes and with normal corneal diameter in 30 eyes). The visual prognosis depended on the phenotype of the more normal eye. Microphthalmos with cyst had the worst prognosis (all worse than 20/400). Microcornea with microphthalmos had a worse prognosis than microcornea without microphthalmos. For microcornea with microphthalmos, 67% saw worse than 20/400. Of the children with microcornea without microphthalmos, 76% saw better than 20/400. Simple coloboma (without microcornea or microphthalmos) had the best visual prognosis: only 7% saw 20/400 or worse. A corneal diameter of less than 6 mm had a poor visual prognosis, whereas a corneal diameter of more than 10 mm had a good prognosis.


Molecular Genetics

In a 5-year-old girl with bilateral morning glory disc anomaly and in a 1-year-old boy with iris anomaly, large coloboma of the optic nerve, retina, and choroid (120200), a remnant of hyaloid vessel proliferation (persistent hyperplastic primary vitreous; see 257910) bilaterally, and growth and mental retardation, Azuma et al. (2003) identified missense mutations in the PAX6 gene (607108.0017 and 607108.0019, respectively).


REFERENCES

  1. Azuma, N., Yamaguchi, Y., Handa, H., Tadokoro, K., Asaka, A., Kawase, E., Yamada, M. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am. J. Hum. Genet. 72: 1565-1570, 2003. [PubMed: 12721955] [Full Text: https://doi.org/10.1086/375555]

  2. Hornby, S. J., Adolph, S., Gilbert, C. E., Dandona, L., Foster, A. Visual acuity in children with coloboma: clinical features and a new phenotype classification system. Ophthalmology 107: 511-520, 2000. [PubMed: 10711890] [Full Text: https://doi.org/10.1016/s0161-6420(99)00140-2]

  3. Jonas, J. B., Freisler, K. A. Bilateral congenital optic nerve head pits in monozygotic siblings. Am. J. Ophthal. 124: 844-846, 1997. [PubMed: 9402835] [Full Text: https://doi.org/10.1016/s0002-9394(14)71706-4]

  4. Savell, J., Cook, J. R. Optic nerve colobomas of autosomal-dominant heredity. Arch. Ophthal. 94: 395-400, 1976. [PubMed: 945057] [Full Text: https://doi.org/10.1001/archopht.1976.03910030183002]


Contributors:
Marla J. F. O'Neill - updated : 8/15/2014
Marla J. F. O'Neill - updated : 8/29/2006
Victor A. McKusick - updated : 5/28/2003
Jane Kelly - updated : 11/21/2000
Victor A. McKusick - updated : 3/27/1998

Creation Date:
Victor A. McKusick : 6/4/1986

Edit History:
carol : 08/18/2014
mcolton : 8/15/2014
carol : 8/30/2006
carol : 8/29/2006
terry : 3/11/2005
mgross : 5/28/2003
mcapotos : 11/21/2000
psherman : 3/27/1998
dholmes : 3/5/1998
mimadm : 6/25/1994
supermim : 3/16/1992
supermim : 3/20/1990
ddp : 10/26/1989
marie : 3/25/1988
marie : 12/15/1986