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chilblain lupus 1 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

chilblain lupus 1

MONDO:0012500

Also known as:chilblain lupusTREX1 chilblain lupuschilblain lupus caused by mutation in TREX1

Overview

Any chilblain lupus in which the cause of the disease is a mutation in the TREX1 gene.

GeneticsAutosomal dominant · TREX1 (chr 3)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Arthralgia, Antinuclear antibody positivity, Chilblains, and Skin ulcer; and common findings: Elevated erythrocyte sedimentation rate and Autoamputation of digits. 9 total HPO annotations.

Organ System	Phenotype Count	Example Features
Skin	3	Abnormal nail morphology, Cutaneous photosensitivity, Skin ulcer

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

TREX1 function has not been fully characterized.

Chilblain lupus 1 is associated with mutations in the TREX1 gene on chromosome 3.

GeneReviews

Clinical Guidance

To date, all pathogenic variants have been frameshift variants in the region of TREX1 encoding the carboxyl terminus of TREX1 . To date no genotype-phenotype correlations have been observed.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

There are no consensus clinical diagnostic criteria for retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).

Suggestive Findings

RVCL-S should be suspected in individuals with the following findings .

Major features

Source: GeneReviews — "Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for chilblain lupus 1. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with RVCL-S

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

There are currently no consensus guidelines for monitoring individuals with RVCL-S. However, close monitoring is recommended. The frequency of monitoring depends on the manifestations and rate of disease progression . Table 6. Recommended Surveillance for Individuals with RVCL-S

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for chilblain lupus 1.

28 publications have been identified in PubMed for chilblain lupus 1. Research spans Case Report / Case Series (56%), Review / Meta-Analysis (19%), and Basic Science / Preclinical (11%).

Research Type	Count	% of Total
Patient case studies	15	56%

Data assembled from 6 of 12 sources · Last updated Sep 17, 2026, 10:29 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:610448

GARD

Genetic and Rare Diseases Info Center

GARD:18493

Questions for Your Care Team

→Should I pursue genetic testing for TREX1, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Due to the systemic nature of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S), the differential diagnosis is quite broad. Following are differential diagnoses specifically for the characteristic and seen in RVCL-S. For other inherited disorders with phenotypic similarities see . Focal and/or Global Brain Dysfunction / MRI Brain Abnormalities Focal and/or global brain dysfunction and MRI brain abnormalities (intracerebral mass lesions and white matter abnormalities) seen in RVCL-S can be similar to intracranial neoplasm, multiple sclerosis, multi-infarct dementia, and central nervous system vasculitis. In these disorders other organs are usually not affected. Moreover, these conditions do not typically follow an autosomal dominant inheritance pattern. • In sarcoidosis and systemic lupus erythematosus (SLE) there can be focal and/or global brain dysfunction as well as involvement of multiple organs, as is seen in RVCL-S. • With sarcoidosis, however, there is frequent involvement of the lungs and skin. No lesions in the lungs have been described in individuals with RVCL-S and skin lesions are not frequently reported . Vascular Retinopathy Vascular retinopathy can occur as a long-term complication of diabetes mellitus and hypertension: • As the vascular retinopathy in RVCL-S is usually observed at a relatively young age (retinopathy has been found in the third decade of life) it is unlikely to be a complication of hypertension or diabetes mellitus, even in those with RVCL-S who have co-occurrence of hypertension or diabetes. • Vascular retinopathy can also be caused by systemic lupus erythematosus, sarcoidosis, and ophthalmologic infections (which are outside of the scope of this GeneReview). • In Susac syndrome, vascular retinopathy and encephalopathy are part of the symptomatology, as is hearing loss, but hearing loss is very rare in RVCL-S. The pattern of white matter lesions seen on MRI may also help to distinguish the two conditions. Table 3. Inherited Disorders to Consider in the Differential Diagnosis of RVCL-S

DifferentialDiagnosisDisorder	Gene(s)	MOI	Clinical Features of the Differential Diagnosis Disorder
NOTCH3	AD	Focal neurologic symptoms; Progressive cognitive decline; Migraine; Mood disturbances; Apathy; White matter lesions on brain imaging; Positive family history	Clinical involvement limited to the brain; The pattern of white matter lesions on brain imaging differs from that in RVCL-S. CARASAL
CTSA	AD	Ischemic stroke; Progressive cognitive decline; Extended white matter lesions on brain imaging; Hypertension	Hemorrhagic strokes occur frequently in CARASAL. CARASIL
HTRA1	AR	Stepwise deterioration in brain functions; Progressive cognitive decline; Extended white matter les...	—

Source: GeneReviews — "Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations"

System/Concern	Evaluation	Comment
Eyes	Ophthalmologic evaluation	Assess for signs of retinopathy, macular edema, glaucoma.
Cardiovascular	Blood pressure	Assess for hypertension.
Renal	Renal function tests1	Consider referral to nephrologist for those w/significant renal insufficiency /or hypertension. Hepatology
Neurologic	Assess cognitive function.	Consider referral to neurologist /or a neuropsychological evaluation. Assess for signs symptoms of migraines.
Endocrinologic	Thyroid function3	Refer to endocrinologist, if clinically significant
Hematologic	Complete blood count	To assess for anemia; consider referral to gastroenterologist for possible occult GI bleeding.
Rheumatologic	Assess for signs symptoms of Raynaud phenomenon.	—
Psychiatric	Assess for psychiatric symptoms.4	Consider psychiatric consultation.
Other	Consultation w/clinical geneticist /or genetic counselor	1. Serum creatinine, BUN, and urinalysis (to include creatinine and protein content) 2. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, gamma-glutamyltransferase (GGT) 3. TSH and free T4 4. It is crucial that unnecessary diagnostic tests not be undertaken.
Treatment of Manifestations in Individuals with Retinal Vasculopathy with RVCL-S Manifestation/Concern	Treatment	Considerations/Other
Visual impairment	Retinal laser therapy	Can prevent slow down progression of retinal involvement that causes visual impairment
Macular edema	Bevacizumab	Elevated eye pressure /
Glaucoma	Standard treatment	—
Hypertension	Standard treatment	May prevent further damage to involved organs
Renal insufficiency	Standard treatment of hypertension	Refer to nephrologist. Renal replacement therapy (incl transplantation) may be considered in severe cases for those w/end-stage renal disease.
Liver function abnormalities	There is no treatment for liver function abnormalities.	Monitor to prevent complications associated w/liver fibrosis to exclude other causes.1 Cerebral vascular
edema	Consider corticosteroid therapy.2	May reduce cerebral vasogenic edema but does not appear to treat the underlying lesion
Migraine	Standard treatment	—
Seizure disorder	Standard treatment w/antiepileptic drugs	Refer to neurologist.
Hypothyroidism	Thyroid replacement therapy	—
Anemia	Standard treatment	Intravenous iron therapy ( in rare cases blood transfusion) may be necessary.
Raynaud phenomenon	Standard treatment	—
Psychiatric concerns	Standard treatment	Refer to psychiatrist or neuropsychologist. When not properly monitored, affected individuals are frequently given incorrect diagnoses and often receive advice to stop drinking alcohol or stop their medication, while this is not required. 2.

Kisho

chilblain lupus 1

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

chilblain lupus 1

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications