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cutis laxa, autosomal dominant 3 (ADCL3) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

cutis laxa, autosomal dominant 3

MONDO:0014706

Also known as:ADCL3cutis laxa, autosomal dominant type 3autosomal dominant cutis laxa 3

Overview

An autosomal dominant cutis laxa characterized by thin skin with visible veins and wrinkles, cataract or corneal clouding, clenched fingers, pre- and postnatal growth retardation, moderate intellectual disability, and a combination of muscle hypotonia with brisk muscle reflexes that has material basis in heterozygous mutation in the ALDH18A1 gene on chromosome 10q24.

GeneticsAutosomal dominant · ALDH18A1 (chr 10)

ResearchLimited published research (4 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.

Features include always present findings: Cloudy or opaque cornea (corneal opacity), Dermal translucency, Low muscle tone (hypotonia), and Prominent forehead and others; and very common findings: Postnatal growth retardation and Feeding difficulties. 33 total HPO annotations.

Organ System	Phenotype Count	Example Features
Eyes	3	Cloudy or opaque cornea (corneal opacity), Strabismus, Developmental cataract

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.

ALDH18A1 encodes aldehyde dehydrogenase 18 family member A1 (795 aa). Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine Highest expression in Cells Cultured fibroblasts (95.6 TPM) and Cells EBV-transformed lymphocytes (93.1 TPM).

Cutis laxa, autosomal dominant 3 is associated with mutations in the ALDH18A1 gene on chromosome 10.

ALDH18A1 is classified as a druggable target (Druggable Genome, Enzyme, and Kinase categories) with score 0.0.

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

No consensus clinical diagnostic criteria for neurocutaneous disorders due to mitochondrial proline synthesis defects have been published.

Suggestive Findings

Neurocutaneous disorders due to mitochondrial proline synthesis defects comprise PYCR1-related autosomal recessive cutis laxa (ARCL), ALDH18A1-related ARCL, and ALDH18A1-related autosomal dominant cutis laxa (ADCL). These disorders should be suspected in probands with the following clinical, laboratory, and imaging findings.

Clinical findings

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 cutis laxa, autosomal dominant 3. The disease remains an area of unmet medical need.

Gene therapy approaches for cutis laxa, autosomal dominant 3 have been reported in the published literature.

GeneReviews

Management Guidelines

No clinical practice guidelines for neurocutaneous disorders due to mitochondrial proline synthesis defects have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with these disorders.

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 7. Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects: Recommended Surveillance

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 cutis laxa, autosomal dominant 3.

5 publications have been identified in PubMed for cutis laxa, autosomal dominant 3. Research spans Case Report / Case Series (50%), Basic Science / Preclinical (25%), and Gene Therapy / Novel Therapeutics (25%).

Recent Publications

Ganjibakhsh M (2025). [PMID: 40158781](https://pubmed.ncbi.nlm.nih.gov/40158781/). *Matrix biology : journal of the International Society for Matrix Biology*. [Gene Therapy / Novel Therapeutics]
Alrefaie SI (2025). [PMID: 40171012](https://pubmed.ncbi.nlm.nih.gov/40171012/). *Clinical case reports*. [Case Report / Case Series]
Chandan S (2025). [PMID: 40018427](https://pubmed.ncbi.nlm.nih.gov/40018427/). *Clinical case reports*. [Case Report / Case Series]
Stanworth M (2024). [PMID: 39480826](https://pubmed.ncbi.nlm.nih.gov/39480826/). *PloS one*. [Basic Science / Preclinical]

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 4:31 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:616603

GARD

Genetic and Rare Diseases Info Center

GARD:16143

Questions for Your Care Team

→Should I pursue genetic testing for ALDH18A1, 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

Clinical Guidance

Neurocutaneous disorders due to mitochondrial proline synthesis defects comprise PYCR1-related autosomal recessive cutis laxa (ARCL), ALDH18A1-related ARCL, and ALDH18A1-related autosomal dominant cutis laxa (ADCL). These disorders are characterized by a generalized progeroid type of cutis laxa with recognizable dysmorphic features and, often, developmental delay . To date, 154 individuals have been reported: 114 with biallelic pathogenic variants in PYCR1 (PYCR1-related ARCL), 27 with biallelic pathogenic variants in ALDH18A1 (ALDH18A1-related ARCL), and 13 individuals with heterozygous de novo pathogenic variants in ALDH18A1 (ALDH18A1-related ADCL). The following description of the phenotypic features associated with this condition is based on these published reports . Table 2. Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects: Frequency of Select Features

Feature	% of Persons w/Feature	Comment
Cutaneous	Lax wrinkled skin	100%
Thin, translucent skin	90%	Visible veins
Neurologic	Developmental delay	98%
Hypotonia	93%	But often brisk reflexes in ALDH18A1-related ADCL
Corpus callosum dysgenesis	55%	—
Athetoid movements	26%	Most frequent in ALDH18A1-related ARCL
Spastic diplegia	10%	Only in ALDH18A1-related ADCL
Growth	IUGR	96%
Postnatal growth deficiency	85%	—
Microcephaly	68%	But neurocranium appears prominent
Relative macrocephaly	10%	Only in ALDH18A1-related ADCL
Connective tissue/ Musculoskeletal	Joint hyperlaxity	98%
Osteopenia	74%	Rarely, fractures
Adducted thumbs/ clubfoot	67%	—
Congenital hip dislocation	53%	—
Wormian bones	49%	—
Hernias	46%	—
Enlarged fontanel w/delayed closure	37%	—
Dysmorphic/Progeroid	95%	Often, prominent chin when older
Ocular	Cataract	58%
Strabismus	40%	—
Blue sclerae	35%	—
Corneal clouding	20%	Most frequent in ALDH18A1-related ARCL and ADCL; less frequent in PYCR1-related ARCL Based on , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Cutaneous features. At birth, all affected individuals have cutis laxa with some degree of skin wrinkling.

Source: GeneReviews — "Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects"

GeneReviews

Differential Diagnosis

Table 4. Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects: Differential Diagnosis

Gene(s)	Disorder	MOI	Key Features of Disorder
ATP6V1E1	V-ATP-ase-related cutis laxa (ARCL2A, 2C, 2D) (See ATP6V0A2-Related Cutis Laxa.)	AR	Generalized cutis laxa; Affected persons shorter than unaffected sibs; Variable intellectual disability; Seizures
BANF1	Nestor-Guillermo progeria syndrome, BANF1-related (OMIM 614008)	AR	Large neurocranium relative to viscerocranium; Aged appearance1
Characteristic facial features w/severely hypoplastic jaw EFEMP1(FBLN3)	EFEMP1-related cutis laxa (ARCL1D) (OMIM 620780)	AR	Translucent skin; Joint laxity2
EFEMP2	EFEMP2-related cutis laxa (ARCL1B)	AR	Thin, translucent skin w/wrinkles
EMILIN1	Arterial tortuosity w/bone fragility syndrome (OMIM 620908)	AR	Thin, translucent skin w/wrinkles; Bone fragility3
FBLN5	FBLN5-related cutis laxa (ARCL1A)	AR	Cutis laxa
GORAB	Geroderma osteodysplasticum, GORAB-related (OMIM 231070)	AR	Generalized cutis laxa (pronounced at hands); Hip dislocation; Short stature; Aged appearance4
Hutchinson-Gilford progeria syndrome	AD	Translucent skin; Large neurocranium relative to viscerocranium; Aged appearance	Characteristic facial appearance; Severe growth deficiency; Atherosclerosis; Osteoporosis; Hair loss
LOX	Arterial tortuosity w/bone fragility syndrome5	AR	Thin, translucent skin w/wrinkles; Bone fragility
LTBP1	Cutis laxa w/craniosynostosis, short stature, brachydactyly, syndactyly, LTBP1-related (OMIM 619451)	AR	Short stature; Cutis laxa6
LTBP4-related cutis laxa (ARCL1C)	AR	Cutis laxa	Congenital emphysema; Congenital diaphragmatic hernia; Downslanted palpebral fissures; Generalized cutis laxa w/thick skin folds; Norm...

Source: GeneReviews — "Neurocutaneous Disorders due to Mitochondrial Proline Synthesis Defects"

Kisho

cutis laxa, autosomal dominant 3

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Biochemical

Skin/wound healing

Neurologic

Development

Growth

Clinical Trials

cutis laxa, autosomal dominant 3

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Biochemical

Skin/wound healing

Neurologic

Development

Growth

Clinical Trials