sudden death

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

Adrenoleukodystrophy, Autosomal

Clinical Characteristics
Ocular Features: 

This early onset and rapidly progressive form of adrenoleukodystrophy is rare.  The early onset and rapidly fatal course of the disease has limited full delineation of the ocular features.  The most striking is the presence of 'leopard-spots' pigmentary changes in the retina.  Polar cataracts, strabismus, and epicanthal folds have also been reported. 

Systemic Features: 

Onset of symptoms occurs shortly after birth often with seizures and evidence of psychomotor deficits.  Rapid neurologic deterioration begins at about 1 year of age with death usually by the age of 3 years.  Hyperpigmentation of the skin may be apparent a few months after birth.  Opisthotonus has been observed.  The ears may be low-set, the palate is highly arched, and the nostrils anteverted.  Frontal bossing may be present.  Serum pipecolic acid and very-long-chain fatty acids (VLCFAs) can be markedly elevated.  Cystic changes in the kidneys have been reported. 

Genetics

This is an autosomal recessive peroxismal disorder resulting from homozygous mutations in receptor gene mutations such as PEX1, PEX5, PEX13, and PEX26.

There is also an X-linked recessive adrenoleukodystrophy (300100) sometimes called ALD but it lacks some of the morphologic features and is somewhat less aggressive. 

Neonatal adrenoleukodystrophy along with infantile Refsum disease (266510, 601539) and Zellweger syndrome (214100) are now classified as Zellweger spectrum or perioxismal biogenesis disorders.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is mainly supportive for associated health problems. 

References
Article Title: 
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