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autosomal recessive cutis laxa type 2 (ARCL2) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

autosomal recessive cutis laxa type 2

MONDO:0019573

Also known as:ARCL2cutis laxa with joint laxity and developmental delay

Overview

A spectrum of connective tissue disorders characterized by the association of wrinkled, redundant and sagging inelastic skin with growth and developmental delay, and skeletal anomalies. The spectrum ranges from patients with classic ARCL2 (ARCL, Debre) type) to patients with a milder form of the disease, wrinkled skin syndrome (WSS).

ResearchLimited published research (3 articles)

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.

GeneReviews

Clinical Guidance

ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. This disorder spans a phenotypic spectrum that includes the historical diagnoses of Debr-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end; these two phenotypes were thought to be distinct clinical entities until their molecular genetic nature was determined. Children diagnosed in the past with Debr-type cutis laxa had more severe developmental and neurologic abnormalities and a less severe cutaneous phenotype than children diagnosed with wrinkly skin syndrome, in whom the skin showed tighter wrinkles and the changes in facial features were milder . To date, about 80 individuals have been identified with a pathogenic variant in ATP6V0A2 [; Authors, unpublished observations]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. ATP6V0A2-Related Cutis Laxa: Frequency of Select Features

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

Suggestive Findings

ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), should be considered in individuals with the following findings.

Clinical Findings

Characteristic signs of cutis laxa

Furrowing of the skin of the whole body; particularly obvious in neck, axillae, and groin

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 autosomal recessive cutis laxa type 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ATP6V0A2-related cutis laxa, 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 ATP6V0A2-Related Cutis Laxa

Prognosis

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

GeneReviews

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with ATP6V0A2-Related Cutis Laxa

System/Concern | Evaluation | Frequency

High myopia other ophthalmic issues

| Ophthalmologic exam, incl refraction for evidence of progressive myopia fundus exam to inspect Bruch's membrane | Annually

Seizures

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 autosomal recessive cutis laxa type 2.

4 publications have been identified in PubMed for autosomal recessive cutis laxa type 2. Kisho has analyzed 3 by research type. Research spans Case Report / Case Series (67%) and Basic Science / Preclinical (33%).

Recent Publications

Chandan S (2025). [PMID: 40018427](https://pubmed.ncbi.nlm.nih.gov/40018427/). *Clinical case reports*. [Case Report / Case Series]
Shangguan S (2024). [PMID: 39172257](https://pubmed.ncbi.nlm.nih.gov/39172257/). *Molecular genetics and genomics : MGG*. [Case Report / Case Series]
Kopp J (2024). [PMID: 39680136](https://pubmed.ncbi.nlm.nih.gov/39680136/). *Cell Mol Life Sci*. [Basic Science / Preclinical]

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 11:55 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:90350

GARD

Genetic and Rare Diseases Info Center

GARD:19134

Questions for Your Care Team

→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

Feature	% of Persons w/Feature	Comment
Cutis laxa	100%	Combination of fine wrinkles sagging skin; can vanish during childhood.
Prominent nasal root	100%	—
Downslanted palpebral fissures	100%	Recognizable facial dysmorphism
Enlarged fontanels w/delayed closure	100%	—
Congenital dislocation of hips	60%	—
Inguinal hernia	60%	—
High myopia	20%	—
Other ophthalmic issues	20%	—
Developmental delay/Intellectual disability	100%	Always speech delay; some can attend normal school
Seizure disorder	100%	Onset variable; may occur as late as adolescence
Neurologic decline	Possibly up to 40%	Unclear; few w/follow-up data
Abnormal brain imaging	90%	Brain malformation experts can make diagnosis from MRI. Presentation and progression. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed.

GeneReviews

Differential Diagnosis

Other disorders characterized by cutis laxa are summarized in . Table 3. Disorders to Consider in the Differential Diagnosis of ATP6V0A2-Related Cutis Laxa

Gene	Disorder	MOI	Clinical Findings	Comment
Cutis laxa	Emphysema	Aneurysms	ID/DD	Bladderdiverticulae
ALDH18A1	De Barsy syndrome A (ARCL3A) (See Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects.)	AR	+	–
ADCL3 (See Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects.)	AD	+	–	–
ATP6V1A	ARCL2D (OMIM 617403)	AR	++	–
ATP6V1E1	ARCL2C (OMIM 617402)	AR	++	–
EFEMP2-related cutis laxa	AR	++	++	+++
ELN	ELN-related cutis laxa (ADCL1)	AD	+	+
EMILIN1	EMILIN1-related cutis laxa1	AR	+	–
FBLN5	FBLN5-related cutis laxa (ARCL1A ADCL2)	ARAD	+++	+++
GORAB	Gerodermia osteodysplastica (GO) (OMIM 231070)	AR	++	–
LTBP4	LTBP4-related cutis laxa (URDS, ARCL1C)	AR	+	++
NBAS	Short stature, optic nerve atrophy, Pelger-Huet anomaly (SOPH syndrome) (OMIM 614800)	AR	+	–
PTDSS1	Lenz-Majewski syndrome hyperostotic dwarfism (LMS) (OMIM 151050)	AD	+	–
PYCR1	De Barsy syndrome B (ARCL3B) (See Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects.)	AR	+	–
ARCL2B (See Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects.)	AR	+	–	–
RIN2	RIN2-related cutis laxa (MACS syndrome) (OMIM 613075)	AR	+	–
Arterial tortuosity syndrome	AR	+	–	++

Source: GeneReviews — "ATP6V0A2-Related Cutis Laxa"

System/Concern	Evaluation	Comment
Inguinal hernia(s)	Clinical eval	Cardiac valvular
dysplasia	Echocardiogram	High myopia other ophthalmic
abnormality	Ophthalmologic exam, incl refraction (for myopia), slit-lamp exam, fundus exam	Slit-lamp exam allows diagnosis of corneal dysplasia (seen in 1 person). DD/ID/ Neurologic abnormality
deficiencies	Full screening, incl von Willebrand factor	—
Genetic counseling	By genetics professionals1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of ATP6V0A2-related cutis laxa to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with ATP6V0A2-Related Cutis Laxa Manifestation/Concern	Treatment	Considerations/Other
Congenital hip dislocation	Standard treatment as recommended by orthopedist	—
Inguinal hernia(s)	Surgical repair	—
High myopia	Standard treatment(s) as recommended by ophthalmologist	—
DD/ID	See .	—
Seizure disorder	Standardized treatment w/ASM by experienced neurologist	See footnote 1.
Self-image difficulties related to cutis laxa	Psychological help as needed	ASM = anti-seizure medication; DD = developmental delay; ID = intellectual disability Education of parents/caregivers regarding common seizure presentations is appropriate.

Kisho

autosomal recessive cutis laxa type 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

High myopia other ophthalmic issues

Seizures

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

autosomal recessive cutis laxa type 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

High myopia other ophthalmic issues

Seizures

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials