corneal leukoma

Rosenthal-Kloepfer Syndrome

Clinical Characteristics

Ocular Features

The major ocular feature associated with this syndrome is a corneal leukoma in one or both eyes.   It consists of a whitish plaque in the epithelium beginning in the inferior nasal quadrant  and later extending into the Bowman layer in patches throughout the entire cornea except for the peripheral one millimeter.  Initially the lesions are flat but later become elevated with some pigmentation at the edges.  The anterior stroma can become vascularized but the epithelial portion does not.  The leukomata are seen as early as the first year of life and are progressive but they are not present in every patient.  The lateral half of the supraorbital arch has a horn-like enlargement.

Systemic Features

Affected individuals are unusually tall and have large hands, feet and chin.  The skin of the hands in the single reported family is described as unusually soft.   The dermal ridge pattern is said to have ‘split ridges’ and may be of diagnostic value even in young children who may not yet have the acromegaloid changes.  The excessive scalp skin undulation differs from the usual cutis verticis gyrate condition by having a coronal orientation as opposed to the usual sagittal folds.  The skin changes may not appear until the fourth or fifth decades of life.   Radiographs show thickening of bone with ‘squaring’ of the middle and proximal phalanges.  There is no evidence of pituitary dysfunction and the sella turcica is normal.

Genetics

Reported pedigrees suggest autosomal dominant inheritance but no locus or gene has been identified.

Treatment Options

Various surgical procedures including penetrating keratoplasty have been used but the most effective seems to be an optical iridectomy to enable patients to use the relatively clear corneal areas.

References

Harbison JB, Nice CM Jr. Familial pachydermoperiostosis presenting as an acromegaly-like syndrome. Am J Roentgenol Radium Ther Nucl Med. 1971 Jul;112(3):532-6.

PubMed ID: 
5570364

ROSENTHAL JW, KLOEPFER HW. An acromegaloid, cutis verticis gyrata, corneal leukoma syndrome. A new medical entity. Arch Ophthalmol. 1962 Dec;68:722-6.

PubMed ID: 
13974983

Strømme Syndrome

Clinical Characteristics

Ocular Features

The core complex of Strømme syndrome consists of intestinal atresia and ocular abnormalities of the anterior segment.  The ocular anomalies seem to be limited to the anterior segment with variable amounts of angle dysgenesis, anterior synechiae, corneal leukoma, and sometimes megalocornea.  Posterior chamber and optic nerve anomalies have been ruled out in a few cases.  Glaucoma has not been reported.  Only about 10 cases have been reported since Strømme 's first report in 1993.  Most patients have been too young for reliable acuity testing.

Systemic Features

The intestinal atresia seems to involve the jejunum primarily and is usually surgically correctable.  Some developmental delay is common while the microcephaly seems to be progressive.  Short stature has been noted and the amount of developmental delay is highly variable.

Genetics

This disorder is presumed to be autosomal recessive but only one family with sibs has been reported and other single cases have been found around the world.  No locus has been identified.

Treatment Options

Infants do well following intestinal surgery.  Ocular surgery has not been reported.

References

Castori M, Laino L, Briganti V, Pedace L, Zampini A, Marconi M, Grammatico B, Buffone E, Grammatico P. Jejunal atresia and anterior chamber anomalies: Further delineation of the Stromme syndrome. Eur J Med Genet. 2010 May-Jun;53(3):149-52.

PubMed ID: 
20219704

van Bever Y, van Hest L, Wolfs R, Tibboel D, van den Hoonaard TL, Gischler SJ. Exclusion of a PAX6, FOXC1, PITX2, and MYCN mutation in another patient with apple peel intestinal atresia, ocular anomalies and microcephaly and review of the literature. Am J Med Genet A. 2008 Feb 15;146A(4):500-4. Review.

PubMed ID: 
18203155

Str√∏mme P, Dahl E, Flage T, Stene-Johansen H. Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly. Clin Genet. 1993 Oct;44(4):208-10.

PubMed ID: 
8261651

Peters Anomaly

Clinical Characteristics

Ocular Features

Peters anomaly occurs as an isolated malformation but also as a feature of other syndromes.  It is often unilateral.  A wide variety of other ocular findings may occur with Peters anomaly as well. Here we limit our description to ‘simple’ Peters anomaly in which the findings are limited to the eye having the classic findings of adhesions of the iris to the posterior cornea and a central or paracentral corneal leukoma.  The lens may also be adherent to the cornea and is often opacified to some degree.  Descemet’s membrane and portions of the posterior stroma are usually missing as well.  Glaucoma is frequently present.  Importantly, there is a wide range in the presentation of clinical features.

Systemic Features

Peters anomaly is a frequent feature of numerous syndromes, both ocular and systemic, among them the Peters-plus (261540) syndrome (sometimes called the Kivlin-Krause (261540) syndrome) and has been reported in a case with aniridia (106210).

Genetics

Isolated Peters anomaly usually occurs in an autosomal recessive pattern but autosomal dominant patterns have been reported as well.  The recessive disorder may be caused by a mutation in several genes, notably PAX6, PITX2CYP1B1, FOXC1, and FOXE3.  The latter gene is also mutated in anterior segment mesenchymal dysgenesis (107250) and congenital primary aphakia (610256).  The variety of clinical features are likely the result of a disruption in some common pathway or pathways.  Mutations in B3GALTL associated with the Peters-Plus syndrome have not been identified in isolated Peters anomaly.

PITX2 is also mutated in ring dermoid of the cornea (180550) and in Axenfeld-Rieger syndrome type 1 (180500).  PAX6 mutations also cause diseases of the cornea, fovea, optic nerve and iris.

Treatment Options

Glaucoma is the most serious threat to vision on Peters anomaly but also the most difficult to treat.  Less than a third of patients achieve control of intraocular pressure even with the most vigorous combinations of therapy.  Corneal opacities can be treated with transplantation but the prognosis is often guarded when glaucoma is present.

From eye bank and other data, it has been estimated that 65% of penetrating keratoplasties in infants for visually significant congenital corneal opacities are performed in patients with Peters anomaly. 

References

Kurilec JM, Zaidman GW. Incidence of Peters Anomaly and Congenital Corneal Opacities Interfering With Vision in the United States. Cornea. 2014 Jun 24. [Epub ahead of print].

PubMed ID: 
24977984

Weh E, Reis LM, Tyler RC, Bick D, Rhead WJ, Wallace S, McGregor TL, Dills SK, Chao MC, Murray JC, Semina EV. Novel B3GALTL mutations in classic Peters Plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes. Clin Genet. 2013 Jul 24. [Epub ahead of print].

PubMed ID: 
23889335

Bhandari R, Ferri S, Whittaker B, Liu M, Lazzaro DR. Peters anomaly: review of the literature. Cornea. 2011 Aug;30(8):939-44. Review.

PubMed ID: 
21448066

Sawada M, Sato M, Hikoya A, Wang C, Minoshima S, Azuma N, Hotta Y. A case of aniridia with unilateral Peters anomaly. J AAPOS. 2011 Feb;15(1):104-6.

PubMed ID: 
213997818

Yang LL, Lambert SR, Lynn MJ, Stulting RD. Surgical management of glaucoma in infants and children with Peters' anomaly: long-term structural and functional outcome. Ophthalmology. 2004 Jan;111(1):112-7.

PubMed ID: 
14711722

Traboulsi EI, Maumenee IH. Peters' anomaly and associated congenital malformations. Arch Ophthalmol. 1992 Dec;110(12):1739-42. Review.

PubMed ID: 
1463415