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familial amyotrophic lateral sclerosis - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

familial amyotrophic lateral sclerosis

MONDO:0005144

Also known as:hereditary amyotrophic lateral sclerosis

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Overview

An instance of amyotrophic lateral sclerosis that is caused by an inherited modification of the individual's genome.

OnsetLATE

TreatmentsNo approved treatments · 1 in pipeline

Clinical Trials6 registered · 4 recruiting

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.

No HPO annotations are available for this condition.

Age of onset: later in life.

GeneReviews

Clinical Guidance

CYLD cutaneous syndrome (CCS) encompasses the clinical phenotypes described in individuals with germline pathogenic CYLD variants. Historically descriptive names including Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT) were assigned on the basis of the predominant tumor type and location; these conditions are now recognized to constitute a clinical spectrum. Individuals with the clinical phenotypes of BSS, FC, and MFT can all present in a single family, and the lack of prognostication offered by these historical labels favors the use of CYLD cutaneous syndrome as a diagnostic term for those with this single gene disorder. Table 2. Features of CYLD Cutaneous Syndrome

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

Formal diagnostic criteria for CYLD cutaneous syndrome (CCS) have not been established.

Suggestive Findings

CYLD cutaneous syndrome should be suspected in an individual with the following findings:

The presence of one or more cylindromas or spiradenomas on the face and scalp, perinasal trichoepitheliomas, or a combination of these tumor types in an individual

Cylindromas, spiradenomas, and trichoepitheliomas can be diagnosed clinically but may mimic other skin tumors, thus requiring confirmatory skin biopsy.

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 familial amyotrophic lateral sclerosis. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for familial amyotrophic lateral sclerosis, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for familial amyotrophic lateral sclerosis. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

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

GeneReviews

Surveillance Guidelines

It is recommended that individuals with CYLD cutaneous syndrome undergo at least annual full skin examination by a dermatologist, with some affected individuals requiring skin review every three to four months.

An assessment of tumor burden and rate of new tumor development can be made, and existing tumors can also be monitored for any signs of malignant transformation.

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.

6 clinical trials registered, 4 recruiting. Interventions under study include other interventions, drug therapy, and medical devices. Pipeline includes 1 PHASE4, 1 PHASE2, 1 PHASE1. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT05923905](https://clinicaltrials.gov/study/NCT05923905)

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 1:11 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Patient Support

Financial & Access Support (External Programs)

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Amyotrophic Lateral Sclerosis Fund

Premium/CopayCurrently AcceptingOperated by HealthWell Foundation

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Amyotrophic Lateral Sclerosis (ALS) Travel & Lodging Assistance

Medical AssistanceCurrently AcceptingOperated by National Organization for Rare Disorders

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Medical References

Questions for Your Care Team

→Are any of the 6 active clinical trials a good fit for my situation?
→What is the current development status of Orgotein for injection, and when might it become available?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Feature1	# of Persons w/Feature	Comment
Phenotype of predominantlycylindromas/spiradenomas	14/26 (54%)	—
Phenotype of predominantly trichoepitheliomas	8/26 (30%)	—
Phenotype of mixed cylindroma/spiradenoma/trichoepithelioma	4/26 (15%)	—
Severe phenotypenecessitatingcomplete scalp excision	6/26 (23%)	In a further study of a Hungarian pedigree,2 5/21 individuals w/a germline pathogenic CYLD variant had this severe phenotype.
Salivary gland tumors	~5%	—
Pulmonary cylindromas	3 persons3	May result in respiratory compromise if lesion affects the large airways Except where otherwise noted, the table summarizes a single study by , which analyzed the clinical features of 26 individuals with germline pathogenic CYLD variants.

GeneReviews

Differential Diagnosis

Disorders with multiple facial papules in the differential diagnosis of CYLD cutaneous syndrome (CCS) are summarized in . Table 3. Disorders with Multiple Facial Papules in the Differential Diagnosis of CYLD Cutaneous Syndrome (CCS)

Gene(s)	Disorder1	Distinguishing Histologic Features in Differential Disorder	Comment
Birt-Hogg-Dub syndrome	Fibrofolliculomas	—	—
NF1	Neurofibromatosis 1 (NF1)	Neurofibromas	Both NF1 CCS are assoc w/lesions on the torso
PTEN	Cowden syndrome(See PTEN Hamartoma Tumor Syndrome.)	Trichilemmomas	TSC1 TSC2
Tuberous sclerosis complex	Angiofibromas	—	—
HR	Marie Unna hypotrichosis 1 (MUHH1)(OMIM 146550)	Trichoepitheliomas2	Severe hair breakage/loss absence of cylindromas in MUHH1 further distinguishes MUHH1 from CCS. PTCH1
Nevoid basal cell carcinoma syndrome	Basal cell nevi	Macrocephaly, broad nasal root jaw cysts	—
Unknown	Multiple syringomas(OMIM 186600)	Syringomas	1. All of the disorders listed are inherited in an autosomal dominant manner. Pilar (trichilemmal) cysts.

Source: GeneReviews — "CYLD Cutaneous Syndrome"

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CYLD cutaneous syndrome (CCS), 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 CYLD Cutaneous Syndrome

System/Concern	Evaluation	Comment
Skin	Skin exam by dermatologist	Full skin exam incl skin of the genitalia; Painful tumors should be identified prioritized for excision .; Education about signs symptoms of malignant transformation1 Histologic exam
Ears/Hearing	Eval of external auditory canals w/otoscope	To screen for tumors that occlude the external auditory canal; When present, clinical assessment for conductive hearing loss may be considered.
Oral	Clinical exam of parotid glands	To screen for salivary lesions
Respiratory	Assessment for signs of respiratory compromise in those w/new onset of shortness of breath, cough, or stridor	If present, radiologic imaging may be necessary to evaluate for pulmonary lesions. Genetic
counseling	Consultation w/clinical geneticist /or genetic counselor	To incl genetic counseling cascade testing where needed Including tumors that are rapidly growing, bleeding, ulcerating or appear different than an affected individual's usual tumors.
Treatment of Manifestations in Individuals with CYLD Cutaneous Syndrome Manifestation/Concern	Treatment	Considerations/Other
Cylindroma, spiradenoma, trichoepithelioma	Removal of tumors by conventional surgery	Repeated surgical procedures to tumor burden typically required1,2; "Scalp-sparing" strategies incl early primary excision, tumor enucleation, excision followed by secondary intention healing techniques recommended;3 avoid removing large areas of scalp.
Malignant tumors	Multidisciplinary team input required to develop management plan	At least 8 different types of malignant tumors are seen in affected persons; w/the exception of BCC, these would be considered rare cancers require appropriate eval following histopathologic assessment .

Source: GeneReviews — "CYLD Cutaneous Syndrome"

Research Type	Count	% of Total
Laboratory research	38	54%
New treatment approaches	10	14%
Disease patterns and progression	8	11%
Patient case studies	6	9%
Research summaries	5	7%
Testing and diagnosis research	2	3%
Clinical study results	1	1%

Kisho

familial amyotrophic lateral sclerosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Patient Support

Financial & Access Support (External Programs)

Are you a patient organization for this condition?

Medical References

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Whole-exome sequencing reveals a novel frameshift and a recurrent nonsense SPG11 variant causing rare familial amyotrophic lateral sclerosis type 5 in two consanguineous Pakistani families.

familial amyotrophic lateral sclerosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Patient Support

Financial & Access Support (External Programs)

Are you a patient organization for this condition?

Medical References

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Whole-exome sequencing reveals a novel frameshift and a recurrent nonsense SPG11 variant causing rare familial amyotrophic lateral sclerosis type 5 in two consanguineous Pakistani families.