cataracts

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: 

Cataracts 46, Juvenile-Onset

Clinical Characteristics
Ocular Features: 

This type of cataract has been found among the Lehrerleut Hutterites and in the population of the Aland Islands, Finland.  It may have its onset in infancy but usually is diagnosed between the ages of 3 to 9 years, beginning as cortical lens opacities and progressing to maturity in 1-3 months.  Some individuals have subcapsular opacifications, both anterior and posterior.  In early stages there may be a diffuse haze throughout the lens.  The degree of opacification can be highly asymmetrical.

Systemic Features: 

A number of Hutterite patients in the reported pedigree have suffered sudden death presumably of arrhythmogenic origin in the third through fifth decades of life.

Genetics

Homozygous mutations in LEMD2 (6p21.32-p21.31) are responsible for this type of cataract.  It is uncertain if sudden death is an association or part of the phenotype resulting from these mutations.  However, all except one of the pedigree members experiencing sudden death had cataracts.   This feature was not mentioned in the 1985 report of juvenile cataracts in the Hutterite population.

The gene product of LEMD2 is expressed in both the mouse and human lens.  Indirect evidence also suggests it plays a role in heart development and cardiomyopathy.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Cataract removal results have been good.

References
Article Title: 

Hutterite-type cataract maps to chromosome 6p21.32-p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death

Boone PM, Yuan B, Gu S, Ma Z, Gambin T, Gonzaga-Jauregui C, Jain M, Murdock TJ, White JJ, Jhangiani SN, Walker K, Wang Q, Muzny DM, Gibbs RA, Hejtmancik JF, Lupski JR, Posey JE, Lewis RA. Hutterite-type cataract maps to chromosome 6p21.32-p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death. Mol Genet Genomic Med. 2015 Nov 14;4(1):77-94.

PubMed ID: 
26788539

Vici Syndrome

Clinical Characteristics
Ocular Features: 

Congenital cataracts, both unilateral and bilateral are common.  The fundus appears hypopigmented. Nystagmus, optic neuropathy, and mild ptosis have been reported.  Nothing is known regarding acuity. 

Systemic Features: 

Infants at birth have striking hypotonia with a weak cry and feeding difficulties.  Dysmorphic features such as micrognathia, microcephaly, low-set ears, some degree of generalized hypopigmentation (hair and skin), and a broad nose with a long philtrum may be present. The face may appear triangular.  Cleft lip and palate may be present.  Evidence of cardiac dysfunction may also be present early with both dilated and hypertrophic cardiomyopathy reported.  Hearing loss has been reported in some individuals.  Recurrent infections are common and immunologic studies have revealed, in some patients, granulocytopenia, low T cell counts (primarily T4+ cells), thymic dysplasia, and low levels of IgG.  Seizures may occur.  Liver dysfunction has been variably reported.

Neurological and brain evaluations have reported agenesis of the corpus callosum, defects in the septum pellucidum, and hypoplasia of the cerebellar vermis along with pontocerebellar hypoplasia.  Psychomotor retardation is severe in most individuals along with general growth retardation.

Histologic studies of skeletal muscle fibers have shown considerable variation in fiber size, centralized nuclei, fucsinophilic inclusions, and enlarged abnormal mitochondria.  Other central nervous system abnormalities include in some individuals a paucity of white matter, schizencephaly, neuronal heterotopias, and enlargement of the ventricles.

The cumulative effects of these multiorgan abnormalities lead to death within the first year or two of life, generally of heart failure or sepsis. 

Genetics

Homozygous or compound heterozygous mutations in the EPG5 gene (18q12.3) have been associated with this condition.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Vici syndrome: a

Byrne S, Dionisi-Vici C, Smith L, Gautel M, Jungbluth H. Vici syndrome: a
review. Orphanet J Rare Dis. 2016 Feb 29;11(1):

PubMed ID: 
4772338

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

Cullup T, Kho AL, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z, Simpson MA, Yau S, Bertini E, McClelland V, Al-Owain M, Koelker S, Koerner C, Hoffmann GF, Wijburg FA, ten Hoedt AE, Rogers RC, Manchester D, Miyata R, Hayashi M, Said E, Soler D, Kroisel PM, Windpassinger C, Filloux FM, Al-Kaabi S, Hertecant J, Del Campo M, Buk S, Bodi I, Goebel HH, Sewry CA, Abbs S, Mohammed S, Josifova D, Gautel M, Jungbluth H. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nat Genet. 2013 Jan;45(1):83-7.

PubMed ID: 
23222957

Spondyloocular Syndrome

Clinical Characteristics
Ocular Features: 

Cataracts have been noted in several patients in the first and second decades of life.  Nystagmus and ‘amblyopia’ have also been reported.  Several individuals have had retinal detachments.

Systemic Features: 

Only a small number of families have been reported.  Poor bone mineralization with frequent fractures in long bones and vertebral compression seem to be consistent features often noted in the first and second decades of life.  Moderate osteoporosis and advanced bone age with platyspondyly may be present.  The vertebral fractures lead to abnormal spinal curvature and may result in shortened stature. 

Some sensorineural hearing loss is sometimes detected in the first decade.  The ears have been described as low-set and posteriorly rotated.  A variety of cardiac defects have been reported including mitral valve prolapse, septal defects, and anomalies of the aortic valve. 

Genetics

This is an autosomal recessive disorder secondary to homozygous mutations in the XYLT2 gene located at 17q21.33. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Pamidronate given intravenously seems to have little therapeutic value.  Hearing aids can be beneficial.  Lensectomy may be of benefit although no reports of cataract surgery have been reported.  Fractures need immediate attention.  Patient may become wheelchair-bound by the second decade.  Special education may be helpful for those with learning difficulties.

References
Article Title: 

CHOPS Syndrome

Clinical Characteristics
Ocular Features: 

There is usually some degree of proptosis and apparent hypertelorism.  The eyebrows are bushy and the eyelashes are luxurious.  One of three patients had cataracts and another had mild optic atrophy.

Systemic Features: 

The overall facial appearance may resemble Cornelia de Lange syndrome with hypertrichosis and a coarse, round facies.  Head circumference is low normal.  Septal defects and a patent ductus arteriosus are often present.  Laryngeal and tracheal malacia predispose to recurrent pulmonary infections and chronic lung disease.  Skeletal dysplasia includes brachydactyly and anomalous vertebral bodies resulting in short stature (3rd percentile).  Genitourinary abnormalities include cryptorchidism, horseshoe kidney, and vesiculoureteral reflux.  Delayed gastric emptying and reflux have been reported.

Genetics

Heterozygous mutations in the AFF4 gene (5q31.1) have been identified in 3 unrelated individuals with this condition.  No familial cases have been identified.  The gene is a core component of the super elongation complex that is critical to transcriptional elongation during embryogenesis.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment for the general disorder.  Tracheostomy was required in 2 of three reported patients. 

References
Article Title: 

Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin

Izumi K, Nakato R, Zhang Z, Edmondson AC, Noon S, Dulik MC, Rajagopalan R, Venditti CP, Gripp K, Samanich J, Zackai EH, Deardorff MA, Clark D, Allen JL, Dorsett D, Misulovin Z, Komata M, Bando M, Kaur M, Katou Y, Shirahige K, Krantz ID. Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat Genet. 2015 Apr;47(4):338-44.

PubMed ID: 
25730767

Hypoparathyroidism, Familial Isolated

Clinical Characteristics
Ocular Features: 

Lens opacities may be present.

Systemic Features: 

The major signs and symptoms result from hypocalcemia. Neuromuscular irritability and various paresthesias may be present.  Some patients have  laryngeal spasm and latent tetany with grand mal seizures.  Alopecia, abnormal dentition and coarse brittle hair may be present.  Cognitive deficits and personality disorders are often a feature.  Brain imaging may show calcification of the basal ganglia.  Serum calcium levels are usually low while phosphorus levels are elevated.   Vitamin D precursor levels are usually low or low normal.

Genetics

Familial hypoparathyroidism may be due to mutations in the PTH gene (11p15.3) (either autosomal dominant or recessive inheritance) or in the GCMB gene (6p24.2) (autosomal dominant inheritance pattern).

There is also an X-linked form of hypoparathyroidism (307700) in which parathryroid tissue may be congenitally absent.

A family has been reported in which hypoparathryroidism was associated with lymphedema (247410) and progressive renal failure.  Ptosis, telecanthus, hypertrichosis, restrictive lung disease, and mitral valve prolapse may also be part of the disorder.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

Normalization of calcium and phosphorus levels is a priority and this may result in some clearing of the lens opacities.  Cataract surgery may be indicated in selected individuals.

References
Article Title: 

Familial Exudative Vitreoretinopathy, EVR6

Clinical Characteristics
Ocular Features: 

Clinical features of this type of exudative retinopathy are based upon the findings in a single large Dutch pedigree containing 16 affected individuals.  The age of onset is unknown but this condition has been described in a 3 year old.  Characteristics of FEVR6 are often seen in individuals during the second or third decades when decreasing vision becomes a challenge.  While some individuals can have normal acuity, others have severe vision loss, often to finger-counting range.

Ocular findings are limited to the fundus consisting of areas of hypo- or hyperpigmentation, dragging of the macula, peripheral retinal avascularity, leaky and stretched capillaries, and exudates.  There may be falciform retinal folds and detachments.  Some patients have white masses of fibrous tissue in or overlying the retina.  Cataracts have been described in several patients.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

FEVR6 results from heterozygous mutations in the ZNF408 gene (11p11.2).  Homozygous mutations in the same gene are responsible for retinitis pigmentosa 72 (616469).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Retinal detachment surgery, while technically difficult, may provide some benefit.

References
Article Title: 

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature

Collin RW, Nikopoulos K, Dona M, Gilissen C, Hoischen A, Boonstra FN, Poulter JA, Kondo H, Berger W, Toomes C, Tahira T, Mohn LR, Blokland EA, Hetterschijt L, Ali M, Groothuismink JM, Duijkers L, Inglehearn CF, Sollfrank L, Strom TM, Uchio E, van Nouhuys CE, Kremer H, Veltman JA, van Wijk E, Cremers FP. ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9856-61.

PubMed ID: 
23716654

Basel-Vanagaite-Smirin-Yosef Syndrome

Clinical Characteristics
Ocular Features: 

The eyes appear abnormally far apart.  Ptosis, microcornea, congenital cataracts, sparse eyebrows, and strabismus are usually present.  Epicanthal folds are often seen.

Systemic Features: 

Psychomotor development is severely delayed and with delay or absence of milestones.  DTRs are often hyperactive but some infants are described as hypotonic.  Some individuals have seizures.  There may be a nevus flammeus simplex lesion on the forehead and body hair is sparse.  Cleft palate, cardiac septal defects, hypospadius, thin corpus callosum and cerebral ventricular dilation have been observed.  The upper lip may have a tented morphology with everted lower lip vermilion. A short philtrum is common. 

Genetics

A homozygous missense mutation in the MED25 gene (19q13.33) has been reported and the transmission pattern is consistent with autosomal recessive inheritance.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No known treatment has been reported.

References
Article Title: 

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

Basel-Vanagaite L, Smirin-Yosef P, Essakow JL, Tzur S, Lagovsky I, Maya I, Pasmanik-Chor M, Yeheskel A, Konen O, Orenstein N, Weisz Hubshman M, Drasinover V, Magal N, Peretz Amit G, Zalzstein Y, Zeharia A, Shohat M, Straussberg R, Monte D, Salmon-Divon M, Behar DM. Homozygous MED25 mutation implicated in eye-intellectual disability syndrome. Hum Genet. 2015 Jun;134(6):577-87.

PubMed ID: 
25792360

Cataracts 13, Congenital, in Adult i RBC Phenotype

Clinical Characteristics
Ocular Features: 

The only ocular signs are dense nuclear cataracts with vision in the range of count fingers or light perception.  The opacities are usuallyrecognized at birth.  Some patients develop nystagmus. 

Systemic Features: 

The Ii blood group is associated with cataracts, most strongly in Asians.  The RBC antigens are developmentally regulated.  Fetal and neonatal RBCs express the i form of the antigen which is gradually converted enzymatically to the I form that normally persists in adults.  The normal Ii adult phenotype is reached before the age of two years. 

Genetics

Homozygous or compound heterozygous deletions of the GCNT2 gene (6p24.3) produce the adult i phenotype (110800) which may or may not be associated with lens opacities.

The GCNT2 gene codes for 3 variants of its product. Mutations that eliminate all 3 GCNT2 variants result in the adult i phenotype in association with congenital cataracts.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Surgery to remove the cataracts may be indicated in some individuals.

References
Article Title: 

Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts

Irum B, Khan SY, Ali M, Daud M, Kabir F, Rauf B, Fatima F, Iqbal H, Khan AO, Al Obaisi S, Naeem MA, Nasir IA, Khan SN, Husnain T, Riazuddin S, Akram J, Eghrari AO, Riazuddin SA. Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts. PLoS One. 2016 Dec 9;11(12):e0167562.

PubMed ID: 
27936067

3-methylglutaconic Aciduria with Cataracts, Neurologic Involvement and Neurtropenia

Clinical Characteristics
Ocular Features: 

Descriptions of ocular findings have been limited.  Congenital nuclear cataracts have been described in one patient but lens opacities have been noted in others.

Systemic Features: 

There is considerable heterogeneity in the phenotype with some patients having minimal signs and living to adulthood whereas others succumb to their disease in the first year of life.  The onset of progressive encephalopathy usually occurs in infancy as evidenced by various movement abnormalities and psychomotor delays.  Neonatal hypotonia sometimes progresses to spasticity.  However, other infants are neurologically normal.  Delayed psychomotor development, ataxia, seizures, and dystonia may be seen.  Brain imaging may reveal cerebellar and cerebral atrophy along with brain stem abnormalities.  Neuronal loss, diffuse gliosis, and microvacuolization have been seen on neuropathologic examination.  Dysphagia is common.  Severe neutropenia and recurrent infections may begin in infancy as well.

Increased amounts of 3-methylglutaconic acid are found in the urine while the bone marrow may contain evidence of arrested granulopoiesis. 

Genetics

This autosomal recessive disorder results from homozygous or compound heterozygous mutations in the CLPB gene (11q13.4).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported for this condition.

References
Article Title: 

CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder

Wortmann SB, Zietkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lucke T, Ounap K, Zordania R, Yaplito-Lee J, van Bokhoven H, Spelbrink JN, Vaz FM, Pras-Raves M, Ploski R, Pronicka E, Klein C, Willemsen MA, de Brouwer AP, Prokisch H, Katsanis N, Wevers RA. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet. 2015 Feb 5;96(2):245-57.

PubMed ID: 
25597510

Pages

Subscribe to RSS - cataracts