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.

Pedigree: 
Autosomal dominant
Treatment
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
Article Title: 

Strømme Syndrome

Clinical Characteristics
Ocular Features: 

The core complex of Stromme syndrome consists of intestinal atresia and ocular abnormalities of the anterior segment.  The ocular anomalies consist of variable amounts of angle dysgenesis, anterior synechiae, corneal leukoma, iris colobomas and hypoplasia, sclerocornea, cataracts, and sometimes microcornea.  However, microphthalmia, tortuous retinal vessels, and optic nerve hypoplasia may also be present.  Hypertelorism and deep-set eyes have been described.  Glaucoma has not been reported.  Only about 10 cases have been reported since Stromme 's first report in 1993.  Most patients have been too young for reliable acuity testing. 

Systemic Features: 

The phenotype is highly variable.  The ears are often large and low-set.  Microcephaly is often present along with a cleft palate and micrognathia.  The intestinal atresia seems to involve the jejunum primarily and is usually surgically correctable.  The duodenum may also be involved and intestinal malrotation has been described.  Myopathic changes in the myocardium have been seen along with small cardiomyoctes.  Microcephaly seems to be progressive.  Short stature has been noted and the amount of developmental delay is highly variable.  Renal hypodysplasia and hydronephrosis have been described.

Some patients seem to develop and function almost normally while more severely affected individuals may not live beyond early infancy or childhood.

Genetics

Compound heterozygous mutations in the CENPF gene (1q41) segregate with this condition. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

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

References
Article Title: 

Stromme Syndrome: New Clinical Features

Stromme Syndrome: New Clinical Features Bayram Ali Dorum, Irmak Tanal Sambel, Hilal Ozkan, Irfan Kiristioglu, Nilgun Koksal APSP J Case Rep. 2017 Mar-Apr; 8(2): 14. Published online 2017 Mar 18.

PubMed ID: 
5371687

Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF

Filges I, Bruder E, Brandal K, Meier S, Undlien DE, Waage TR, Hoesli I, Schubach M, de Beer T, Sheng Y, Hoeller S, Schulzke S, Rosby O, Miny P, Tercanli S, Oppedal T, Meyer P, Selmer KK, Stromme P. Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF. Hum Mutat. 2016 Jan 28. doi: 10.1002/humu.22960. [Epub ahead of print].

PubMed ID: 
26820108

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, PITX2,  CYP1B1, 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.

This is a genetically and clinically heterogeneity condition as whole genome sequencing reveals numerous additional gene mutations in patients with both syndromic and 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.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
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
Article Title: 

Whole exome sequence analysis of Peters anomaly

Weh E, Reis LM, Happ HC, Levin AV, Wheeler PG, David KL, Carney E, Angle B, Hauser N, Semina EV. Whole exome sequence analysis of Peters anomaly. Hum Genet. 2014 Sep 3. [Epub ahead of print].

PubMed ID: 
25182519
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