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Sjogren-Larsson Syndrome

Clinical Characteristics

Ocular Features

The retina often has glistening white intraretinal dots which may be concentrated in the macula.  They have been found in 1 to 2 year old infants.  The macula may have ‘punched out’ lesions.  A pigmentary retinopathy is present in about 50% of patients and fluorescein angiography reveals a mottled hyperfluorescence. The cornea often has grayish stromal opacities that become vascularized, most commonly in the lower half.  Most patients have punctate keratitis resulting in marked photophobia.  Visual acuities can range from about 20/40 to finger counting.  The retinal changes may be progressive but EOG and ERG studies do not reveal abnormalities of retinal function.  VEPs though are often abnormal.  Ichthyosis may involve the lids and periorbital areas.

Systemic Features

The skin changes are present at birth and consist of an ichthyosiform erythroderma.  Hyperkeratosis is also present at birth and full blown ichthyosis develops during infancy.  The skin changes are most marked about the neck, flexion creases, and lower abdomen.  Scales in these areas are often darker than the surrounding skin.  Mental retardation may be mild to severe and spastic diplegia or quadriplegia is common but there is little evidence of progression.  There does not seem to be any correlation of age with the severity of neurological disease.

Genetics

Mutations in the ALDH3A2 gene (17p11.2) are responsible for this autosomal recessive disorder resulting in a deficiency of fatty aldehyde dehydrogenase. This can lead to long-chain fatty alcohol accumulation as demonstrated in the brain with proton magnetic resonance spectroscopy.

A form of Sjogren-Larsson syndrome with more severe neurologic signs is caused by recessive mutations in ELOVL4 (6p14,1),  Mutations in the same gene have been identified in patients with autosomal dominant Stargardt disease 3 (600110).

Treatment Options

No treatment is available for this disorder but moisturizing skin treatments can be beneficial.

References

Aldahmesh MA, Mohamed JY, Alkuraya HS, Verma IC, Puri RD, Alaiya AA, Rizzo WB, Alkuraya FS. Recessive Mutations in ELOVL4 Cause Ichthyosis, Intellectual Disability, and Spastic Quadriplegia. Am J Hum Genet. 2011 Nov 16. [Epub ahead of print]

PubMed ID: 
22100072

Lossos A, Khoury M, Rizzo WB, Gomori JM, Banin E, Zlotogorski A, Jaber S, Abramsky O, Argov Z, Rosenmann H. Phenotypic variability among adult siblings with Sjögren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80.

PubMed ID: 
16476818

Willemsen MA, Cruysberg JR, Rotteveel JJ, Aandekerk AL, Van Domburg PH, Deutman AF. Juvenile macular dystrophy associated with deficient activity of fatty aldehyde dehydrogenase in Sjogren-Larsson syndrome. Am J Ophthalmol. 2000 Dec;130(6):782-9.

PubMed ID: 
11124298

Rogers GR, Rizzo WB, Zlotogorski A, Hashem N, Lee M, Compton JG, Bale SJ. Genetic homogeneity in Sjøgren-Larsson syndrome: linkage to chromosome 17p in families of different non-Swedish ethnic origins. Am J Hum Genet. 1995 Nov;57(5):1123-9.

PubMed ID: 
7485163