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Cataracts and Ichthyosis

Clinical Characteristics
Ocular Features: 

Cortical cataracts have been reported.

Systemic Features: 

Icthyosis is associated with cataracts in some family members.

Genetics

Three families have been reported in which cataracts and ichthyosis were associated.  Two male offspring of normal Japanese parents had cortical cataracts and ichthyosis.  In another family of unknown ethnicity, three sisters had cataracts but only two had ichthyosis.  In a third in which the mother had cataracts and ichthyosis, two of her female children had cataracts.

Treatment
Treatment Options: 

Treatment is unknown.

References
Article Title: 

Progeroid Short Stature with Pigmented Nevi

Clinical Characteristics
Ocular Features: 

The presence of cataract has been reported.   One patient with keratoconus, endothelial dystrophy, and chronic conjunctivitis required a corneal transplant for a perforated ulcer.  Another individual with endothelial dystrophy, keratoconus, dry eye syndrome, and conjunctivitis developed OCT evidence of progressive retinal thickening and folding of inner retinal layers.  Retinal electrodiagnostic tests were normal.   Few patients have had complete ocular examinations, however.

Systemic Features: 

Short stature beginning in utero is characteristic and general growth parameters are usually in the third percentile.  The appearance of premature aging is suggested by a pinched bird-like facies and lack of facial subcutaneous fat.  Striking cutaneous pigmented nevi are present and may increase in number throughout life.  Joint mobility is limited to about half of normal.  The voice is often characteristically high-pitched.  Hypodontia and irregular dentition are often seen.

There may be an immunodeficiency as reflected by susceptibility to recurrent infections due to subnormal numbers of B and T cells.  Cognitive abilities are subnormal and some decline in adulthood has been reported.  Some individuals have been considered mentally retarded.  Agitation, touch hypersensitivity, depression, panic attacks, and severe insomnia may be present.  Sensorineural hearing loss is common.  Males may have hypospadias while females experience premature puberty and premature menopause.

Genetics

Consanguinity among some parents suggests autosomal recessive inheritance but no locus or mutation have been identified.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatnent has been reported.

References
Article Title: 

Albinism, Oculocutaneous, Type V

Clinical Characteristics
Ocular Features: 

The phenotype in the two families studied includes photophobia, nystagmus, foveal hypoplasia and decreased visual acuity.  The fundus is hypopigmented.

Systemic Features: 

The hair is golden-colored and the skin is described as white. 

Genetics

The specific gene causing this form of oculocutaneous albinism has not been identified.  However, an area of homozygosity in the region of 4q24 has been identified in 6 members in two families belonging to a large consanguineous Pakistani pedigree in which it segregates with the OCA5 phenotype. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for oculocutaneous albinism but appropriately tinted glasses could be beneficial.

References
Article Title: 

Increasing the complexity: new genes and new types of albinism

Montoliu L, Gronskov K, Wei AH, Martinez-Garcia M, Fernandez A, Arveiler B, Morice-Picard F, Riazuddin S, Suzuki T, Ahmed ZM, Rosenberg T, Li W. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res. 2014 Jan;27(1):11-18. Review.

PubMed ID: 
24066960

Fibrosis of Extraocular Muscles with Synergistic Divergence

Clinical Characteristics
Ocular Features: 

This is an ocular motility disorder with restrictive ophthalmoplegia and anomalous eye movements.  Some individuals exhibit Marcus Gunn jaw winking and downgaze fixation along with ptosis.  MRI imaging may reveal hypoplasia of the oculomotor nerve and absence of the abducens nerve.  Sometimes one or more extraocular muscles are replaced with fibrous tissue.  Globe retraction may accompany the abduction movement.  Forced duction testing may reveal severe restriction and Bell's phenomenon may be absent.  Vertical nystagmus and jerky eye motions may accompany attempted fixation.  There is considerable asymmetry to the extraocular movements of the two eyes. 

Systemic Features: 

Some patients have oculocutaneous hypopigmentation.

Genetics

No specific mutation has been identified.  Several examples of parent to child transmission have been reported suggesting autosomal dominant inheritance.

Other nonsyndromal forms of congenital fibrosis of extraocular muscles include: CFEOM1 (135700), CFEOM2 (602078), CFEOM3C (609384), and CFEOM5 (616219), although the eye movement phenotype may vary.  See also Tukel CFEOM syndrome (609428).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Ptosis and strabismus surgery may be of benefit.

References
Article Title: 

Macular Dystrophy, Vitelliform 1

Clinical Characteristics
Ocular Features: 

This is an uncommon form of vitelliform macular dystrophy and may not be a unique disorder.  Onset of disease is usually later than in the classic Best disease due to mutations in the Best1 gene.  Only slight to moderate vision impairment is present. Small drusen-like lesions may be seen in the foveal areas along with macular or extramacular punctate yellow lesions.  Importantly, the EOG light/dark Arden ratio is often normal or only slightly impacted even when severe loss of vision is present.  It has been claimed that fundus fluorescein angiography is diagnostically more reliable than the EOG.  Patchy RPE depigmentation is often present in the central and the peripheral retina as well as in the peripapillary area.

The clinical features resemble vitelliform macular dystrophy resulting from mutations in the IMPG1 and IMPG2 genes. 

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

No mutation or locus has been found to segregate with VMD1 disease.  However, it is probably a unique condition since other VMD-causing mutations such as those in Best1PRPH2, IMPG1, and IMPG2 have been ruled out in a number of families.

The transmission pattern is consistent with autosomal dominant inheritance.

Genotyping has identified at least 5 forms of vitelliform macular dystrophy.  In addition to the iconic Best disease (VMD2, 153700) apparently first described by Friedreich Best in 1905 and now attributed to mutations in the Best1 gene, we know of at least 4 more and specific mutations have been identified in three.  Other forms are VMD3 (608161) due to mutations in the PRPH2 gene, VMD4 (616151) resulting from mutations in the IMPG1 gene, and VMD5 (616152) caused by mutations in the IMPG2 gene.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for this disease but low vision devices may be helpful.

References
Article Title: 

Familial Exudative Vitreoretinopathy, EVR3

Clinical Characteristics
Ocular Features: 

Abnormal retinal angiogenesis with retinal ischemia is the development defect that leads to the clinical features of the familial exudative vitreoretinopathies.  It is usually bilateral.  There is considerable clinical heterogeneity in the appearance of both the retina and the vitreous but common to all is the presence of peripheral areas of avascularity in the retina that may be seen in newborns.  This may only be visible using fluorescein angiography in mild cases.  The vessels may be hyperpermeable resulting in patchy exudates in the retina.  Neovascularization often develops with retinal and vitreous bleeding and eventually retinal traction resulting in retinal folds and detachments. Severe disease with early onset may result in blindness in infants but milder disease may be asymptomatic even as adults.  Cataracts may result.

The ocular disease may be confused with retinal dysplasia (as seen in pseudogliomas and Norrie disease [310600]) or retinopathy of prematurity.

Systemic Features: 

 No systemic features have been reported in EVR3.

Genetics

This is likely an autosomal dominant disorder based on pedigree evidence but no specific mutation has been found.  A disease locus at 11p13-p12 has been identified by linkage studies, located near the FZD4 gene containing the mutation responsible for EVR1.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Appropriate vitreoretinal surgery to release vitreous traction and to repair retinal detachments should be considered.  Cataract removal may be beneficial.  Low vision aids could be helpful in milder cases with residual vision.

References
Article Title: 

Microphthalmia, Syndromic 10

Clinical Characteristics
Ocular Features: 

Microphthalmia seems to be a common feature.  The globes have anterior-posterior dimensions of 5-8 mm.  No internal ocular structures can be visualized and individuals are likely blind.  The corneal diameters in two patients were measured at 3-4 mm.  The optic nerves have been described as ‘slender’ on brain imaging.

Systemic Features: 

Head circumference ranges from the 10th to the 25th percentile at birth  Psychomotor development has been described as normal during the first 6 to 8 months but is followed by rapid deterioration in performance with spasticity, vomiting and continuous crying.  An MRI on one 3 day old patient was reported as normal while at 15 months of age there was atrophy of the vermis and corpus callosum and at 8 years of age the atrophy of these structures was even more extensive.  Similar atrophy patterns were seen in the two other patients and eventually all cerebral while matter is lost and there is atrophy of the brainstem as well. 

Genetics

Three children from 3 consanguineous Pakistani families have been reported but no locus or mutation has been identified.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Corneal Dystrophy, Band-Shaped

Clinical Characteristics
Ocular Features: 

Symptoms of ocular irritation with tearing, conjunctival injection and decreased vision can be present at birth but more often is evident later in the first decade of life.  The band is located in the cornea in the palpebral fissure area in a horizontal pattern.  Apparently no other lesions are present in the eye.    

Systemic Features: 

None reported.

Genetics

Only three families with familial, isolated band keratopathy have been reported.  These were described in the mid-twentieth century and it is possible that they had underlying ocular and corneal disease.  In one family 3 of 9 children, the product of a first-cousin mating, were affected consistent with autosomal recessive inheritance.  In two of these the keratopathy was first noted during puberty while it was present at birth in the third child.

 In another family the band keratopathy was seen in a brother and sister at 11 and 16 years old.

In the third family a father and son were affected.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

Topically applied EDTA solutions are sometimes effective in removing lesions consisting of calcium deposits but this has not been reported to be effective in the hereditary form of band keratopathy. 

References
Article Title: 

Microphthalmia, Syndromic 4

Clinical Characteristics
Ocular Features: 

In several generations of an Irish family, 7 males with clinical anophthalmia were identified.  Ankyloblepharon was also present and X-rays of the orbits were identified.

Systemic Features: 

One patient was born with a cleft soft palate and had preauricular skin tags.  All individuals were considered to be mentally retarded with IQ's less than 50.

Genetics

MCOPS4 is an X-linked condition based on a single reported family.  The responsible mutation has not been identified but a locus (Xq27-q28) likely to contain the gene has been identified by multipoint linage analysis.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Blepharocheilodontic Syndrome

Clinical Characteristics
Ocular Features: 

The eyelids are disproportionately large with an associated lagophthalmos and lower lid ectropion.  The upper eyelids may have a double row of lashes (distichiasis).  Hypertelorism and a broad nasal root have been reported.

Systemic Features: 

A cleft lip and palate are major features and are usually bilateral.  The teeth are conically shaped with microdontia and oligodontia (involving both primary and secondary dentition) often present as well.  Several newborns have had an imperforate anus. Scalp hair may be sparse and hypoplastic nails have been described.  Hypothyroidism and thyroid agenesis has been documented in several patients.

Genetics

This is an autosomal dominant condition but no causative mutation has been identified.

Other conditions with distichiasis include Blatt distichiasis (126300) and lymphedema-distichiasis (153400).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment consists of correction of individual anomalies such as eyelid, oral, and dental malformations.

References
Article Title: 

Blepharo-cheilo-dontic (BCD) syndrome

Gorlin RJ, Zellweger H, Curtis MW, Wiedemann HR, Warburg M, Majewski F, Gillessen-Kaesbach G, Prahl-Andersen B, Zackai E. Blepharo-cheilo-dontic (BCD) syndrome. Am J Med Genet. 1996 Oct 16;65(2):109-12.

PubMed ID: 
8911600

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