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Cataracts, Congenital, with Cleft Palate

Clinical Characteristics
Ocular Features: 

Bilateral congenital cataracts are usually present together with upward-slanting and narrowed lid fissures.  The upper eyelids appear abnormally thick and epicanthus is common.  Nothing is known about the location or morphology of the lens opacities.

Systemic Features: 

Anomalies of the palate consisting of clefting, bifid uvula, and sub-mucous clefts are consistently present.  Oral anomalies such as thickening of the lower lid and small mouth are commonly seen.  The nose may be both long and broad.  The face usually appears oval and the forehead is prominent.  A cartilaginous nodule often appears on the helix of low-set and anteriorly rotated ears.  The fingers may be long and thin.

No cardiac or neurologic defects have been reported.

Genetics

Based on the transmission pattern in the single 4 generation family reported, autosomal dominant inheritance is likely.  Array comparative genomic hybridization revealed an interstitial amplification at Xp21.1 but this did not segregate precisely with the clinical pattern and is possibly a copy number polymorphism.  Both sexes are about equally affected. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No data on vision or surgical treatment have been reported but surgery for cleft palate and cataracts may be indicated.

References
Article Title: 

Blue Diaper Syndrome

Clinical Characteristics
Ocular Features: 

A single patient has been reported with microcornea, optic nerve hypoplasia, and 'abnormal' eye movements.  The full ocular phenotype is unknown but 'visual problems' are sometimes mentioned in other reports.

Systemic Features: 

Nephrocalcinosis and blue urine are the major systemic manifestations of blue diaper syndrome.  Symptoms of fever, constipation, poor weight gain, failure to thrive, and irritability can also be part of the syndrome.

Genetics

This is considered an autosomal recessive disorder although an X-linked defect cannot be ruled out since reported patients have been male.  Parental consanguinity is present in some families.  Nothing is known about the mutation or its locus.  Intestinal transport of tryptophan is defective and bacterial degradation results in excessive indole production.  Oxidation in the urine to indigo blue results in the characteristic discoloration.        

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Restriction of dietary tryptophan has been suggested.

References
Article Title: 

Chorioretinal dysplasia, microcephaly, and mental retardation

Clinical Characteristics
Ocular Features: 

The ocular phenotype has not been well defined in this condition since few families have been reported.  Microphthalmia is present in some patients.  The corneas may be small and there is often some conjunctival growth over the limbus.

The retinal features consist of lacunar depigmentation of the RPE and in some cases resemble the lesions of congenital toxoplasmosis.  Eighty to 90 per cent of patients have areas of atrophic and dysplastic-appearing lesions of the retina and choroid with vascular attenuation.  The edges of lacunae may have patchy hyperpigmentation.  These lesions are usually static but may show mild progression.  Visual acuity is generally stable or only mildly progressive.  However, other patients have a severe reduction in acuity.  ERG responses are reduced.

Systemic Features: 

The amount of microcephaly may be minimal and at least some patients have 'bulging' foreheads.  The amount of mental deficiency varies from mild to severe.  IQ levels are generally in the range of 60-70.   Hypotonia has been reported in more severe cases.  Skull size is usually 2-3 standard deviations below the mean and generally has some frontal prominence.

Genetics

This seems to be an autosomal dominant disorder although no loci or mutations have been identified.  It is likely that the category of disease known as microphthalmia-chorioretinal syndrome consists of a heterogeneous group of disorders.  No locus or specific mutation has been identified.

It differs from the microcephaly, lymphedema, chorioretinopathy syndrome (152950) in which retinal folds, ptosis and lymphedema are associated with a typical facial phenotype.  For other disorders in this database having a somewhat similar phenotype see: chorioretinopahty and microcephaly type 1 (251270) and type 2 (616171).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment is supportive.  Low vision aids may be helpful.

References
Article Title: 

Iridogoniodysgenesis and Skeletal Anomalies

Clinical Characteristics
Ocular Features: 

Megalocornea, congenital glaucoma, a concave iris with stromal atrophy and corectopia, and deep anterior chambers are typical ocular features.  High myopia has been reported and retinal detachments have been observed.  Glaucoma control can be difficult to achieve and there is a significant risk of cataracts and phthisis bulbi following surgery.  Posterior embryotoxon has not been observed.

Systemic Features: 

Facial features seem to be consistent.  The forehead is wide, the nose appears broad with a large nasal tip and broad nares although the bridge appears narrow.  The philtrum is long and wide.  The ears may appear large and the neck is short.  The thorax is abnormally wide and the nipples are widely spaced and umbilicated.  The long bones are slender with thin cortices and wide metaphyses.  There is generalized osteopenia.  Vertebral bodies are cuboid-shaped with narrow vertebral canals and enlarged apophyses

Genetics

Two non-consanguineous families each with 3 sibs have been reported suggesting autosomal recessive inheritance.  Nothing is known about the mutation or its locus.

The ocular features may resemble Rieger or Axenfeld anomaly but these are inherited in autosomal dominant patterns and the skeletal features are dissimilar.       

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Vigorous treatment of glaucoma is indicated but successful control, even with surgery, is difficult to achieve.

References
Article Title: 

Wildervanck Syndrome

Clinical Characteristics
Ocular Features: 

The ocular manifestations of this disorder are limited to Duane syndrome and abducens palsy.

Systemic Features: 

Congenital perceptive deafness is due to a bony malformation of the inner ear.   A Klippel-Feil cervical malformation consisting of a low hairline, limited neck mobility, and short neck secondary to cervical fusion (usually involving the atlas and axis) is present as well. The presence of neck webbing (pterygium colli) can exaggerates the short neck appearance.  Diastematomyelia of the lower medulla and cervical cord has been reported in a child who also had tonsillar herniation and hydrocephalus of all three ventricles.

A variety of inconsistent anomalies including spine deformities, cardiac malformations, anomalies of the genitourinary system and somatic growth retardation have also been reported.

The KFS malformation can occur alone or in association with other syndromes.

Genetics

This is a heritable syndrome that affects primarily females.  The inheritance pattern, however, is not clear.   Sex-linked dominance with lethality in the male has been proposed but others have suggested multifactorial inheritance.  Most cases occur sporadically and no responsible genes have been identified.

Treatment
Treatment Options: 

Patients might benefit from cochlear implants as well as strabismus surgery to correct a head turn.

References
Article Title: 

Organoid Nevus Syndrome

Clinical Characteristics
Ocular Features: 

The sebaceous nevi often involve the eyelids, cornea, and conjunctiva.  Dermoids and lipodermoids are also seen.  Iris and choroidal colobomas are often present.  The sclerae may contain cartilage and bone which can be visible on CAT scans.  Depending upon the structures involved, patients may have strabismus, nystagmus, ptosis, exposure keratitis, and nerve palsies.

 

Systemic Features: 

Phakomatous lesions on the skin seem to preferentially occur on the upper part of the body including the face, neck and scalp but they may occur anywhere on the body including the oral cavity.  Initially they appear as papules but become verrucous around puberty.  Malignant transformation is seen in 15-20 per cent of patients.

Mental retardation and seizures are often seen in the first year of life.  Milestones achieved during that time are often lost subsequently.  Generalized weakness, osteopenia, and intracranial aneurysms are features in some patients.  Bone involvement may be highly asymmetrical.

Biopsies of conjunctival lesions show choristomas containing hyperplastic sebaceous and apocrine glands along with hair follicles.

Genetics

No clear genetic basis exists for this disease.  However, several families with multigenerational involvement have been reported in an autosomal dominant pattern.  It has been suggested that the disorder may result from a dominant lethal gene that allows some patients to survive by chance mosaicism.

Treatment
Treatment Options: 

No treatment is available for the generalized disease but therapy for specific symptoms such as epilepsy may be helpful.

References
Article Title: 

Ophthalmic features of the organoid nevus syndrome

Shields JA, Shields CL, Eagle RC Jr, Arevalo F, De Potter P. Ophthalmic features of the organoid nevus syndrome. Trans Am Ophthalmol Soc. 1996;94:65-86; discussion 86-7. Review.

PubMed ID: 
8981690

Blepharoptosis, Myopia, Ectopia Lentis

Clinical Characteristics
Ocular Features: 

A mother and 2 daughters with ectopia lentis, myopia, and blepharoptosis have been reported.  The axial length of the globes was increased in the mother and one of the daughters while the myopia in the other daughter with ectopia lentis was presumably lens-induced as the equator bisected the visual axis (axial length approximately 25mm).  The upper lid creases were considered to be abnormally high but levator function was good, consistent with levator aponeurosis disinsertion.  Extraocular movements were normal.  

Systemic Features: 

No systemic abnormalities were present.  More specifically, there was no evidence of Ehlers-Danlos (225400) or Marfan syndrome (154700).

Genetics

The presence of similar findings in a mother and 2 daughters suggests autosomal dominant inheritance but no locus has been identified. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Displaced lenses may need to be removed. 

References
Article Title: 

Oculopharyngodistal Myopathy

Clinical Characteristics
Ocular Features: 

Progressive ptosis, which may be asymmetric, is an early sign.  Extraocular palsy occurs as well. 

Systemic Features: 

The mean age of onset of this progressive disease is 22 years.  Pharyngeal and distal limb muscles seem to be primarily involved.  Weakness in masseter, facial, and bulbar muscles have been observed but no muscle group seems to be spared.  Atrophy of facial muscles is common and may be pronounced.  There is considerable variability in expression, particularly in the degree of limb weakness which often appears by the fifth decade.  Swallowing difficulties can be severe.  Respiratory weakness may be evident relatively early, even while patients are still ambulatory.  Loss of ambulation most commonly occurs by the third or fourth decade after the onset of first symptoms.  Serum creatine kinase levels are mildly elevated and histologic changes show chronic myopathic changes with rimmed vacuole formation.  No changes have been found in the central or peripheral nervous system. 

Genetics

The causative mutation has not been identified but mutations causing other forms of hereditary myopathy have been ruled out.  Most families are consistent with autosomal dominant inheritance but the pattern in at least one family has suggested a recessive pattern indicating genetic heterogeneity. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Supportive treatment such as physical and respiratory therapies may be helpful but no specific treatment is available for the muscle disease.

References
Article Title: 

Oculopharyngodistal myopathy

Satoyoshi E, Kinoshita M. Oculopharyngodistal myopathy. Arch Neurol. 1977 Feb;34(2):89-92.

PubMed ID: 
836191

Microphthalmia with Coloboma, X-Linked

Clinical Characteristics
Ocular Features: 

Isolated colobomatous microphthalmia is caused multiple mutations and usually inherited in an autosomal dominant pattern.  Type 1 is an X-linked disorder with typical features of small eyes, small corneas, colobomas, and elevated intraocular pressures. 

Systemic Features: 

By definition no systemic disease is present. 

Genetics

The combination of colobomas and microphthalmia is found in numerous heritable syndromes but also occurs in isolation.  X-linked syndromes with this combination usually include mental retardation and cataracts but these are absent in the isolated type described here.  A locus on the X chromosome was identified to lie either on the proximal short arm or the proximal long arm but no specific mutation or gene has been identified.  In the single multigenerational reported family, all affected individuals were male except for one female in whom non-random X-inactivation was postulated. 

Syndromal forms of X-linked microphthalmia with coloboma (309800 ) have also been reported.

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

No treatment is available for the malformations but low vision aids should be considered for appropriate individuals. 

References
Article Title: 

Cone Dystrophy, Peripheral

Clinical Characteristics
Ocular Features: 

Several families have been reported in which rod function was normal while cone function was impaired, more so peripherally than centrally.  Visual acuity ranges from normal to 20/200.  Color vision may be normal in some patients while others have some degree of dyschromatopsia.  Full-field ERG cone responses are reduced significantly but focal macular cone ERGs are normal.   Visual fields are normal except for small paracentral scotomas.  Temporal pallor has been noted in the optic discs of 2 patients.  Cone responses on ERG were demonstrated to decrease in one patient during a 4 year interval.  Photophobia as commonly seen in cone-rod dystrophies was not reported.  No abnormalities are seen on fundus examination or fluorescein angiography. 

Systemic Features: 

No systemic disease has been reported. 

Genetics

No responsible mutation has been reported.  Two of the three reported patients were siblings born to presumably unaffected parents, compatible with autosomal recessive inheritance. 

It is questionable whether a 'pure' cone dystrophy exists as most patients have evidence (at least eventually) of both rod and cone disease.  However, an autosomal dominant form of cone dystrophy (602093) has been reported in which cone dysfunction predominates and evidence of rod damage occurs much later.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available but visual function can be enhanced with low vision aids.  

References
Article Title: 

Peripheral cone disease

Pinckers A, Deutman AF. Peripheral cone disease. Ophthalmologica. 1977;174(3):145-50.

PubMed ID: 
854266

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