congenital cataracts

Ayme-Gripp Syndrome

Clinical Characteristics
Ocular Features: 

Most patients have congenital cataracts which may be mild and "oil drop" in appearance.  The eyes appear far apart, the eyebrows are broad, and the palpebral fissures may slant upward or downward.  Ptosis has been reported.  Aphakic glaucoma has been reported in one juvenile who had unilateral cataract surgery at 5 months of age.

Systemic Features: 

The phenotype is heterogeneous and not all patients have all features.  The facial features are said to resemble those of the Down syndrome with brachycephaly, a high forehead, and a flat midface with shallow orbits and malar hypoplasia.  The ears are small, low-set, and posteriorly rotated.  The nose is short and the nasal bridge is broad and flat.  The mouth is small and the upper lip is thin.  The scalp hair may be sparse and the nails sometimes appear dystrophic.

The fingers are sometimes brachydactylous and tapered.  Short stature is common and the joints may have limited motion.  Dislocation of the radial heads is seen rarely while radioulnar synostosis has been seen in a few individuals.  Postnatal short stature is common.

Seizures often occur.  The ventricles appear large and cerebral atrophy has been reported.  Intellectual disability and mental retardation are common. However, at least one individual attended university although he had been diagnosed in childhood with Asberger disease.   Neurosensory hearing loss is common.

Genetics

This autosomal dominant condition results from heterozygous mutations in the MAF (16q32.2) gene.  At least one mother/son transmission event has been reported.

Many of the same features are seen in what has been called the Fine-Lubinsky syndrome (601353) but without mutations in the MAF gene.  It may not be a unique disorder.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No general treatment has been reported but specific anomalies such as cataracts should be addressed.

References
Article Title: 

Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies

Niceta M, Stellacci E, Gripp KW, Zampino G, Kousi M, Anselmi M, Traversa A, Ciolfi A, Stabley D, Bruselles A, Caputo V, Cecchetti S, Prudente S, Fiorenza MT, Boitani C, Philip N, Niyazov D, Leoni C, Nakane T, Keppler-Noreuil K, Braddock SR, Gillessen-Kaesbach G, Palleschi A, Campeau PM, Lee BH, Pouponnot C, Stella L, Bocchinfuso G, Katsanis N, Sol-Church K, Tartaglia M. Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies. Am J Hum Genet. 2015 May 7;96(5):816-25.

PubMed ID: 
25865493

Cataracts, Congenital, With Short Stature and Minor Skeletal Anomalies

Clinical Characteristics
Ocular Features: 

Early-onset cataracts are the main ocular feature of this syndrome.  A nonconsanguineous Korean family with 4 affected individuals has been reported.  Cataracts were diagnosed at various ages, including one adult, one juvenile, and one infant.  All had horizontal nystagmus and reduced vision even after surgical removal of the lenses.  

Systemic Features: 

Macrocephaly and short stature are consistent features.  Brachydactyly of the fingers is usually present.  The feet are described as "flat" and contain accessory navicular bones.

Genetics

A 3 generation Korean family with 4 affected members has been reported.  Three living members and a deceased grandfather had cataracts in an autosomal dominant pattern.  A mutation in the BRD4 gene (19p12.12) mutation segregated with the cataract phenotype.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Surgical removal of the cataractous lenses may be helpful in selected individuals but amblyopia is likely present as postoperative vision may remain below normal.

References
Article Title: 

Hyperphosphatasia with Mental Retardation Syndrome 6

Clinical Characteristics
Ocular Features: 

Congenital cataracts may be present.  The eyes appear deeply-set and strabismus has been seen in severely affected cases.   

Systemic Features: 

Two families have been reported.  The range of severity in symptoms is wide.  Birth may occur prematurely especially in the presence of polyhydramnios.  Postnatal development can be complicated by seizures, chronic lung disease, developmental regression, and renal disease.  Poor growth secondary to feeding difficulties have been reported.  Death can occur in early childhood.

Dysmorphic features include a short neck, bitemporal narrowing, depressed nasal bridge, and proximal limb shortening.  Osteopenia, flexion contractures, and hip dysplasia may be present.  Dilatation of the renal collecting system with increased echogenicity have been reported.  Creatine kinase and serum alkaline phosphatase may be increased and muscle histology shows small, atrophic fibers with increased fibrosis and considerable variations in fiber size.

Genetics

Homozygous mutations in the PIGY gene (4q22.1) resulting in deficiencies of glycosylphosphatidylinositol synthesis have been associated with this condition.  

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported.

References
Article Title: 

Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

Ilkovski B, Pagnamenta AT, O'Grady GL, Kinoshita T, Howard MF, Lek M, Thomas B, Turner A, Christodoulou J, Sillence D, Knight SJ, Popitsch N, Keays DA, Anzilotti C, Goriely A, Waddell LB, Brilot F, North KN, Kanzawa N, Macarthur DG, Taylor JC, Kini U, Murakami Y, Clarke NF. Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies. Hum Mol Genet. 2015 Nov 1;24(21):6146-59.

PubMed ID: 
26293662

Cataracts 45

Clinical Characteristics
Ocular Features: 

Dense white cataracts have been diagnosed as soon as 2 weeks after birth.

Systemic Features: 

No dysmorphic features or psychomotor deficits have been found.

Genetics

Homozygous mutations in the SIPA1L3 gene (19q13.1-q13.2) were found in a consanguineous German family in which 2 of 3 female sibs were affected.   The parents were phenotypically normal but heterozygous for the mutation.    

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Surgical removal has apparently been successful.

References
Article Title: 

Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization

Greenlees R, Mihelec M, Yousoof S, Speidel D, Wu SK, Rinkwitz S, Prokudin I, Perveen R, Cheng A, Ma A, Nash B, Gillespie R, Loebel DA, Clayton-Smith J, Lloyd IC, Grigg JR, Tam PP, Yap AS, Becker TS, Black GC, Semina E, Jamieson RV. Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization. Hum Mol Genet. 2015 Oct 15;24(20):5789-804.

PubMed ID: 
26231217

Microcephaly, Congenital Cataracts, and Psoriasiform Dermatitis

Clinical Characteristics
Ocular Features: 

Congenital cataracts are usually present.  No further description is available.  Some individuals have a chronic blepharitis.

Systemic Features: 

Small stature, microcephaly, and developmental delay are important features. The skin in early life, even in infancy, may have an psoriasiform dermatitis that waxes and wanes in some patients while others have only dry skin.  Chronic arthralgias are sometimes present leading to joint contractures especially in the lower extremities.  Skeletal maturation is delayed and there may be cognitive deficits.

Serum total cholesterol levels are generally low but triglycerides are in the normal range.  Serum levels of IgE and IgA may be elevated.  This condition results from defects in the cholesterol synthesis pathway.

Genetics

Compound heterozygosity or homozygosity of mutations in the SC4MOL gene (4q32.3) (also known as MSMO1) is responsible for this condition.  Parents with a single mutation may have mildly elevated plasma methylsterol levels.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Cholesterol supplementation and the use of statins has been reported to improve symptoms.  The usual treatments for psoriasis may provide some temporary relief.  Physical therapy may prevent joint contractures.  Antibiotic drops or ointment may be helpful in the treatment of blepharitis.

References
Article Title: 

The role of sterol-C4-methyl oxidase

He M, Smith LD, Chang R, Li X, Vockley J. The role of sterol-C4-methyl oxidase
in epidermal biology. Biochim Biophys Acta. 2014 Mar;1841(3):331-5. Review.

PubMed ID: 
24144731

Cataracts, Congenital, Deafness, Short Stature, Developmental Delay

Clinical Characteristics
Ocular Features: 

The facial features superficially resemble those often seen in Down syndrome patients with slanting (up or down) lid fissures and epicanthal folds. The amount of ptosis is variable.  Lens opacities are usually congenital in origin.  Hypopigmentation of the macula has been noted in two individuals.

Systemic Features: 

The characteristic facies may be evident at birth and requires karyotyping to rule out the trisomy of Down syndrome. Brachycephaly and a flat face may be present.  The mouth is often small and the nasal tip is shortened while the philtrum is long and smooth.  Some degree of intellectual disability and neurosensory hearing loss soon become evident.  There is postnatal growth delay and most individuals are short in stature.  The ears are low-set and rotated posteriorly.

The skeletal anomalies are not fully delineated but one patient had bilateral radioulnar synostosis while hip chondrolysis requiring hip replacement has been seen in two adult individuals.  Limited motion may be present in some joints, both large and small.  Seizures have been reported in a few individuals. Nails may appear dystrophic and there are variable tooth anomalies present. 

Genetics

The responsible heterozygous mutations are in the MAF gene (16q22-q23).  Type 4 (CCA4) (610202) autosomal dominant cerulean cataracts with multiple morphologies may also result from mutations in this transcription factor gene.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No general treatment for this condition is known.  Congenital cataracts can be removed.  Some patients may benefit from special education.   Seizure medications may be indicated and some patients can benefit from hearing aids.  Severe joint disease may require replacement.

References
Article Title: 

Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies

Niceta M, Stellacci E, Gripp KW, Zampino G, Kousi M, Anselmi M, Traversa A, Ciolfi A, Stabley D, Bruselles A, Caputo V, Cecchetti S, Prudente S, Fiorenza MT, Boitani C, Philip N, Niyazov D, Leoni C, Nakane T, Keppler-Noreuil K, Braddock SR, Gillessen-Kaesbach G, Palleschi A, Campeau PM, Lee BH, Pouponnot C, Stella L, Bocchinfuso G, Katsanis N, Sol-Church K, Tartaglia M. Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies. Am J Hum Genet. 2015 May 7;96(5):816-25.

PubMed ID: 
25865493

CODAS Syndrome

Clinical Characteristics
Ocular Features: 

Dense nuclear cataracts can be seen by six months of age.  Some patients have ptosis. The fundi have been described as normal at one month of age in a single infant but vision was described at the 20/200 level at 2 years of age.  Cataracts noted at 4 months had been removed.

Systemic Features: 

Patients have multiple severe systemic abnormalities.  There is generalized developmental delay along with mild microcephaly and hypotonia.   The forehead is often broad while the face appears flattened with anteverted nares, a flat nasal bridge, a short philtrum, low-set and crumpled ears.  Infants may have an inadequate upper respiratory apparatus with atrophic vocal cords and some die of laryngeal obstruction in the first days of life.  Sialorrhea and difficulty swallowing have been noted.  Mild to moderate neurosensory hearing loss is often present but there may also be a conduction component to this. 

Brain imaging has revealed large ventricles, with subcortical hypomyelination, a thin corpus callosum, and prominent cortical sulci.  The vertebrae may have coronal clefts and scoliosis often develops. Generalized metaphyseal dysplasia and delayed bone age are usually present.  The anus may be imperforate and a rectovaginal fistula and cryptorchidism have been reported.  Long bones may be malformed as well and most patients are short in stature. Delayed dentition, enamel dysplasia, and abnormal cusp morphology are often present.  Cardiac septal defects may be seen.

Genetics

Homozygous mutations in LONF1 (19p13.3) segregate with the phenotype.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no general treatment available and infants sometimes die from laryngeal obstruction in the first days of life.   Individual anomalies may be surgically correctable in selected individuals.  Occasional infants are stillborn but one patient died an accidental death at 14 years of age. 

References
Article Title: 

CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease

Strauss KA, Jinks RN, Puffenberger EG, Venkatesh S, Singh K, Cheng I, Mikita N, Thilagavathi J, Lee J, Sarafianos S, Benkert A, Koehler A, Zhu A, Trovillion V, McGlincy M, Morlet T, Deardorff M, Innes AM, Prasad C, Chudley AE, Lee IN, Suzuki CK. CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease. Am J Hum Genet. 2015 Jan 8;96(1):121-35.

PubMed ID: 
25574826

Cataracts, Growth Hormone Deficiency, and Skeletal Dysplasia

Clinical Characteristics
Ocular Features: 

Lens opacities can be seen in infancy or childhood and may be congenital in onset.  Nystagmus has been noted in one patient. 

Systemic Features: 

There is considerable clinical heterogeneity in the phenotype.  Motor milestones may be slightly delayed.  Dysmorphic features in at least some individuals include bushy eyebrows, a prominent forehead, and a small mouth.  Thoracic scoliosis and genu valgum may be present.  Physical growth is reduced during infancy and childhood resulting in a short stature in adulthood.  Growth hormone and cortisol deficiency have been documented. Episodic hypoglycemia has been documented. The pituitary adenohypophysis appears atrophied on MRI.

Neurosensory hearing loss has been diagnosed in the first two years of life.  A distal sensory neuropathy with loss of pain, temperature and touch sensation may be present late in the first decade of life.  There are no cognitive deficits and patients can live independently.

Genetics

This is likely an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the IARS2 gene (1q41).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Appropriate hormonal replacement therapy can be beneficial.  Individual skeletal surgery for scoliosis and hip dislocation should be considered.  Visually significant lens opacities may require surgery.

References
Article Title: 

Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA Synthetase IARS2 in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome

Schwartzentruber J, Buhas D, Majewski J, Sasarman F, Papillon-Cavanagh S, Thiffaut I, Sheldon KM, Massicotte C, Patry L, Simon M, Zare AS, McKernan KJ; FORGE Canada Consortium, Michaud J, Boles RG, Deal CL, Desilets V, Shoubridge EA, Samuels ME. Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA Synthetase IARS2 in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome. Hum Mutat. 2014 Nov;35(11):1285-9.

PubMed ID: 
25130867

Cataracts, Congenital, with Intellectual Disability

Clinical Characteristics
Ocular Features: 

Reported patients have bilateral posterior polar lens opacification, presumably present since birth.  No other ocular abnormalities are present.  Vision is stated to be normal following early cataract extractions.  No glaucoma has been detected while spectral OCT and electrophysiological studies had normal results.

Systemic Features: 

Psychomotor disabilities and developmental delays are present.  Walking does not occur until the age of about 2 years and speech is present by 5 years.  No dysmorphic features or other organ disease are present.  MRI studies of the brain are normal.

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the STX3 gene (11q12.1).  It has been reported in three children in a consanguineous Tunisian family.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Surgical removal of the cataracts should be considered when visually significant.  Special education might be helpful as learning difficulties have been noted.

References
Article Title: 

Cataracts, Congenital Zonular Pulverulent 3

Clinical Characteristics
Ocular Features: 

Bilateral dust-like lens opacities are diagnosed at a median age of 5 years but have been seen at 6 months of age.  These affect the embryonal, fetal, and infantile nucleus and are often surrounded by snowflake- or needle-like opacities throughout the lens cortex.  The dust-like particles may be multicolored and impart a haze to the lens.  Evidence for progression is suggested by the fact that about half of such affected patients require cataract surgery as adults.  No other ocular abnormalities are present.

There is considerable phenotypic heterogeneity.

Systemic Features: 

No systemic abnormalities are associated.

Genetics

Heterozygous mutations in GJA3 (13q11) seem to be responsible for the opacities.  For another somewhat similar form of autosomal dominant congenital cataract see Cataracts, Congenital Zonular Pulverulent 1 (116200).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Visually significant cataracts may be removed.

References
Article Title: 

Pages

Subscribe to RSS - congenital cataracts