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retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Anhidrosis; and very common findings: Low blood cell counts (all types) (pancytopenia) and Enlarged spleen (splenomegaly). 8 total HPO annotations.

Organ System	Phenotype Count	Example Features
Skin	2	Anhidrosis, Urticaria
Blood and immune system	2	Low blood cell counts (all types) (pancytopenia), Enlarged spleen (splenomegaly)
Brain and nerves	1	Migraine
Metabolism	1	Recurrent fever
Digestive system	1	Enlarged spleen (splenomegaly)

GeneReviews

Clinical Guidance

ALPK1-related autoinflammatory disease (ALPK1-AD) is characterized by clinical findings that can include intraocular inflammation, retinal degeneration, recurrent fever, deforming arthritis, and headaches. Anhidrosis/hypohidrosis with associated findings of enamel and caries, short dental roots, and hyposalivation are common. Most adults have ophthalmologic manifestations; however, vision loss is not universal . Although significant intrafamilial variability can occur, most individuals with ALPK1-AD exhibit at least one clinical or laboratory feature (e.g., episodic elevation of serum markers of inflammation such as C-reactive protein). To date, 41 individuals from 19 families with a pathogenic variant in ALPK1 have been described [, , , , ]. The following description of the phenotypic features associated with this condition is based on these reports . Table 2. ALPK1-Related Autoinflammatory Disease: Frequency of Select Features

Feature	Frequency	Comment
Optic nerve elevation	++	Present on initial eval for most persons

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 retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for ALPK1-related autoinflammatory disease (ALPK1-AD) have been published. In the absence of established clinical practice guidelines, the authors offer the recommendations discussed in this section based on their collective experience in working with more than 15 families over a period of five years. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ALPK1-AD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. ALPK1-Related Autoinflammatory Disease: Recommended Evaluations Following Initial Diagnosis

System/Concern	Evaluation	Comment
Ophthalmic	Ophthalmologic eval	By specialists in uveitis retinal disorders /or ophthalmic genetics; Determine need for referral to low vision services.
Systemic	By rheumatologist	Experience in managing systemic inflammation recommended Anhidrosis/
Hypohidrosis	Assess severity of hypohidrosis, incl episodes of hyperthermia.	Evaluate for history of heat intolerance anhidrosis. Dental abnormalities
Genetic counseling	By genetics professionals1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of ALPK1-AD to facilitate medical personal decision making Family support
resources	By clinicians, wider care team, family support organizations

Source: GeneReviews — "ALPK1-Related Autoinflammatory Disease"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "ALPK1-Related Autoinflammatory Disease"

Clinical Trials

1 trial found

Explore Trials

Prognosis

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

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. ALPK1-Related Autoinflammatory Disease: Recommended Surveillance

System/Concern	Evaluation	Frequency
Systemic autoinflammatory disease	Per treating clinician	Per treating clinician Anhidrosis/
Hypohidrosis	Assess severity treatment response for hypohidrosis.	Annually /or as needed Dental
Family/Community	Assess family need for social work support or follow-up genetic counseling if new questions arise (e.g., family planning.	As needed ERG = electroretinogram; FA = fluorescein angiography; OCT = optical coherence tomography

Source: GeneReviews — "ALPK1-Related Autoinflammatory Disease"

Phenotype severity distribution: 1 always present feature, 2 very common features, 2 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

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.

1 clinical trial registered, 1 recruiting. Interventions under study include drug therapy. Pipeline includes 1 PHASE1. Research is primarily industry-sponsored.

113 publications have been identified in PubMed for retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome. Research spans Review / Meta-Analysis (38%), Case Report / Case Series (21%), and Other (18%).

Research Type	Count	% of Total
Research summaries	39	38%
Patient case studies	21	21%
Other research	18	18%
Laboratory research	12	12%
Testing and diagnosis research	6	6%
Disease patterns and progression	3	3%
Clinical study results	2	2%
New treatment approaches	1	1%

Recent Publications

Wang X (2026). [PMID: 41448386](https://pubmed.ncbi.nlm.nih.gov/41448386/). *Prog Retin Eye Res*. [Review / Meta-Analysis]
Varghese D (2026). [PMID: 41520798](https://pubmed.ncbi.nlm.nih.gov/41520798/). *Surv Ophthalmol*. [Case Report / Case Series]
Gupta A (2026). [PMID: 35593815](https://pubmed.ncbi.nlm.nih.gov/35593815/). *Unknown Journal*. [Other]
Mohankumar A (2026). [PMID: 37276292](https://pubmed.ncbi.nlm.nih.gov/37276292/). *Unknown Journal*. [Other]
Musa MJ (2026). [PMID: 35881754](https://pubmed.ncbi.nlm.nih.gov/35881754/). *Unknown Journal*. [Other]
Khouri P (2026). [PMID: 42203680](https://pubmed.ncbi.nlm.nih.gov/42203680/). *Ophthalmic Genet*. [Case Report / Case Series]
Vegunta S (2026). [PMID: 30422472](https://pubmed.ncbi.nlm.nih.gov/30422472/). *Unknown Journal*. [Other]
Ganguli A (2026). [PMID: 42112140](https://pubmed.ncbi.nlm.nih.gov/42112140/). *Kidney Med*. [Case Report / Case Series]
Anilkumar AC (2026). [PMID: 28613684](https://pubmed.ncbi.nlm.nih.gov/28613684/). *Unknown Journal*. [Other]
Li HY (2026). [PMID: 41587563](https://pubmed.ncbi.nlm.nih.gov/41587563/). *Diabetes Care*. [Review / Meta-Analysis]

Kisho

retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team