Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers

Study Overview
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Brief Summary
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Sjogren-Larsson syndrome (SLS) is a rare genetic disease in which patients typically exhibit ichthyosis (dry, scaly skin), intellectual disability, spasticity, seizures and a distinctive maculopathy. The purpose of this study is to define the clinical spectrum and natural history of Sjogren-Larsson syndrome, and identify biomarkers that correlate with disease phenotype while establishing a registry for future investigations of biochemical pathogenesis and therapy.

Detailed Description
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The study will consist of a clinical component and a scientific component consisting of laboratory investigations of potentially useful biochemical (lipid and protein) markers. Up to 50 SLS patients of all ages, gender and ethnic origins will be enrolled. A detailed clinical evaluation will be performed to determine the presence and extent of disease involving the skin, nervous system and eyes. Clinical testing will include brain magnetic resonance imaging (MRI) and spectroscopy (MRS), electroencephalography (EEG), neurocognitive tests, ophthalmologic examination with retinal photographs and optical coherence tomography (OCT), photographs of the skin and tests of cutaneous transepidermal water loss. Laboratory investigations will include lipid analyses (e.g. fatty alcohols, farnesol, fatty acids, ether glycerolipids, etc.) of blood, skin and urine; proteomic analysis of skin (stratum corneum); and measurements of leukocyte fatty alcohol and farnesol oxidation. A skin biopsy (optional) will be obtained for electron microscopy, measurement of lanthanum perfusion (transepidermal water loss), and/or establishing keratinocyte cultures. Correlations between clinical abnormalities and laboratory measurements will be tested to identify the most useful biomarkers for future diagnostic and therapeutic studies. To characterize the progression of phenotypic features over time, patients <6 years of age will be followed yearly and patients ≥6 years of age will be followed every 3 years. In addition, a SLS patient registry will be established as a resource for future investigations in SLS.

Official Title
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Sjogren-Larsson Syndrome: A Longitudinal Study of Natural History, Clinical Variation and Evaluation of Biochemical Markers

Conditions
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Sjogren-Larsson Syndrome (SLS)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The only eligibility criterion is that subjects have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome. Exclusion Criteria: The primary exclusion criteria are the patients' failure to consent or inability to travel to a STAIR site.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sjogren-Larsson syndrome<br>There are no cohorts for this study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome (SLS). | Determine the spectrum of clinical disease severity and changes in severity of symptoms over time. Each organ system will be evaluated using validated clinical exams (for example, Modified Ashworth Spasticity Score for neurologic severity) or categorical tests (such as EEG normal or abnormal). The clinical data will be used to develop a quantitative SLS severity score whereby patients will be described (for example, overall severity 1 to 5 with score 1 being the mildest phenotype and score 5 being the most severe). These quantitative outcome measures will be followed over time to assess disease progression. | 2017 (up to 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify biomarkers that correlate with disease severity. | Blood, urine and skin biomarkers will be explored to identify tests that correlate with clinical severity of SLS. Multiple tests will be performed and outcome measures will be statistically compared to the clinical severity score to determine correlation coefficients, which will be used to establish new biomarkers for SLS. | 2017 (up to 5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ichthyosis, spasticity, spastic diplegia, intellectual disability