Prepair 1000+

Gene: CTNS

Green List (high evidence)

Well established gene disease association.
Cystinosis is a multisystemic lysosomal storage disease resulting from a defect in cystine transport out of lysosomes. This results in cystine accumulation affecting all tissues; the eyes and kidneys are the first organs to be affected. Cell damage and organ dysfunction are heterogeneous and vary in severity and progression. Cystinosis leads to severe renal Fanconi syndrome, characterized by polyuria, polydipsia, failure to thrive, vomiting, constipation, dehydration, impaired longitudinal growth, and/or hypophosphatemic/calcipenic rickets. Corneal crystals increase with age resulting in photophobia, corneal sensitivity, and reduced visual acuity if left untreated. Very rarely, patients not treated for ocular crystals may develop corneal lesions severe enough to require a corneal transplant.
Individuals can develop endocrine, cardiovascular, and neurological involvement as well as other non-specific symptoms (e.g., gastrointestinal involvement, heat intolerance, (hypophoresis) due to cystine buildup later in life. Serious non-renal manifestations usually develop in the second decade of life.

There are three main clinical forms of the disease:
1. The most severe and common subtype is infantile nephropathic cystinosis (95% of cases) MIM#219800 - failure to thrive usually reported after first 6 months of life, corneal crystals can occur prior to 1 year of age, and ocular involvement usually after 3 years old. Without treatment, progression to end stage renal disease and death prior to 10 years old.
Subtype of this condition - Cystinosis, atypical nephropathic MIM#219800, where Fanconi syndrome and renal disease are present without additional symptoms. (PMID: 1244226).
2. Juvenile (or intermediate) nephropathic cystinosis (~3% of cases) MIM#219900 - onset ~8-10 years of age. Progression to end stage renal failure occurs later than infantile form.
3. Adult non-nephropathic (ocular) cystinosis - MIM# 219750 characterized clinically only by photophobia, absent renal disease.
Clingen has lumped 3 phenotypes into a single disease name: "Cystinosis - CTNS" - no reported evidence of differences in molecular mechanisms.

Animal model present - mouse.
Note: 57kb deletion accounts for 50% of pathogenic alleles in patients of Northern European ancestry.

Created: 24 Oct 2024, 11:57 a.m. | Last Modified: 24 Oct 2024, 11:57 a.m.

Panel Version: 1.486

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cystinosis, nephropathic MIM#219800; Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, atypical nephropathic MIM#219800

Publications

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