What are the most serious health complications of cutis laxa, and what symptoms should prompt immediate medical attention?

Cutis laxa can affect internal organs, leading to serious complications. You should seek immediate medical attention for symptoms such as sudden difficulty breathing, chest pain, severe abdominal pain, signs of a stroke (like sudden weakness or numbness on one side of the body, vision changes, or trouble speaking), or any new, severe pain or swelling, as these could indicate issues with the heart, lungs, blood vessels, or intestines.

Are there any treatments or management strategies specifically for the loose, sagging skin associated with cutis laxa?

Currently, there is no specific medical treatment to reverse the loose, inelastic skin characteristic of cutis laxa. Surgical interventions, such as plastic surgery, may be considered to improve the appearance of sagging skin, particularly on the face or neck. However, the results are often temporary due to the underlying connective tissue defect, and the skin may stretch again over time. Management primarily focuses on addressing internal organ complications and providing supportive care.

Since cutis laxa can be inherited, what are the chances of passing it on to my children, and are there genetic tests available?

Most cases of cutis laxa are inherited, meaning they are caused by genetic changes passed down through families. The inheritance pattern can vary depending on the specific gene involved (autosomal dominant, autosomal recessive, or X-linked). Genetic counseling can help determine the specific inheritance pattern in your family and assess the risk for future children. Genetic testing is available to identify the underlying gene mutations in many forms of inherited cutis laxa.

What kind of ongoing medical monitoring is typically recommended for someone diagnosed with cutis laxa, especially regarding internal organ involvement?

Regular, comprehensive medical monitoring is crucial for individuals with cutis laxa. This often includes routine heart evaluations (like echocardiograms) to check for heart problems or blood vessel abnormalities, lung function tests to monitor for emphysema, and imaging studies (such as ultrasound or CT scans) to check for hernias or diverticula in the bladder or intestines. The specific monitoring schedule will depend on the individual's symptoms and the organs affected.

Cutis laxa

Cutis laxa is a rare connective‑tissue disorder that produces loose, inelastic skin and can involve the heart, blood vessels, lungs, and other organs; most cases are inherited, while a minority are acquired later in life.

Overview

Cutis laxa is a disorder of connective tissue, the tissue that provides structure and strength to muscles, joints, organs, and skin. Most cases are inherited, but some are acquired, which means they do not appear to be caused by genetic variations. While signs and symptoms of inherited cutis laxa are often noticeable in infancy or childhood, acquired cutis laxa typically appears later in life. This summary primarily describes inherited forms of cutis laxa.

The term “cutis laxa” is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy or wrinkled appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin.

Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical blood vessels. Affected individuals may have soft out‑pouchings in the lower abdomen (inguinal) or around the belly button (umbilical hernia). Sacs called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a life‑long lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life‑threatening.

Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X‑linked. In general, the autosomal recessive forms tend to be more severe than the autosomal dominant forms, although some people with autosomal dominant cutis laxa are severely affected. In addition to the features described above, people with autosomal recessive cutis laxa can have delayed development, intellectual disability, seizures, problems with movement, or eye or bone abnormalities.

The X‑linked form of cutis laxa is often called occipital horn syndrome. This form is considered a mild type of Menkes syndrome, which affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge‑shaped calcium deposits in the occipital bone, coarse hair, and loose joints.

Other rare conditions, including arterial tortuosity syndrome, geroderma osteodysplastica, and RIN2 syndrome, are sometimes classified as cutis laxa‑related conditions because affected individuals can have loose, sagging skin. These conditions each have a particular pattern of signs and symptoms affecting different tissues and body systems.

Frequency

Cutis laxa is a rare disorder. More than 450 affected families worldwide have been reported.

Causes & Risk Factors

Cutis laxa can be caused by variants (mutations) in several genes. Autosomal dominant cutis laxa (ADCL), the most common form, is primarily caused by variants in the ELN gene. Very rarely, FBLN5 and ALDH18A1 gene variants are associated with autosomal dominant forms. Autosomal recessive cutis laxa (ARCL) can be caused by variants in the FBLN5, EFEMP2, LTBP4, ATP6V0A2, PYCR1, or ALDH18A1 genes.

Many of the genes associated with autosomal dominant and autosomal recessive forms are involved in the formation and function of elastic fibers, slender bundles of proteins that provide strength and flexibility to connective tissue throughout the body. Elastic fibers allow the skin to stretch, the lungs to expand and contract, and arteries to handle high‑pressure blood flow.

The major component of elastic fibers, a protein called elastin, is produced from the ELN gene. Other proteins involved in cutis laxa that have critical roles in elastic‑fiber assembly are produced from the EFEMP2, FBLN5, LTBP4, and ATP6V0A2 genes. Variants in any of these genes disrupt the formation, assembly, or function of elastic fibers, weakening connective tissue in skin, arteries, lungs, and other organs.

Two other genes, ALDH18A1 and PYCR1, encode proteins important for the synthesis of the amino acid proline, a key component of elastic‑fiber proteins, and for mitochondrial function. Alterations in these genes appear to disrupt mitochondria, potentially leading to death of connective‑tissue cells that support the skin. It is unclear whether disrupted proline formation directly contributes to cutis laxa.

The X‑linked form, occipital horn syndrome, is caused by variants in the ATP7A gene, which regulates copper levels. Reduced copper supply decreases activity of copper‑containing enzymes needed for bone, skin, hair, blood‑vessel, and nervous‑system structure and function; the resulting enzyme deficiency underlies the signs of occipital horn syndrome.

Variants in the genes described above account for only a small percentage of all cases. Additional, as‑yet‑unidentified genes can also cause the condition.

About 20 percent of cases are acquired, meaning they do not appear to be caused by gene variants. Acquired cutis laxa appears later in life and is related to destruction of normal elastic fibers. The causes are unclear, but it may follow an infection, an inflammatory skin episode (e.g., eczema or hives), or as a side effect of copper‑chelating medications.

Genes associated with Cutis laxa

ALDH18A1
ATP6V0A2
ATP7A
EFEMP2
ELN
FBLN5
LTBP4
PYCR1

Additional Information from NCBI Gene:

ATP6AP1
ATP6AP2
ATP6V1A
ATP6V1E1

Inheritance

Cutis laxa can have an autosomal dominant, autosomal recessive, or X‑linked recessive pattern of inheritance.

Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this form are caused by variants in the ELN gene; rarely, FBLN5 or ALDH18A1 variants can also follow this pattern.

Variants in FBLN5, EFEMP2, LTBP4, ATP6V0A2, PYCR1, and ALDH18A1 genes can cause autosomal recessive cutis laxa. Autosomal recessive inheritance means both copies of the gene in each cell have variants; the parents each carry one copy but typically show no signs.

Occipital horn syndrome has an X‑linked recessive pattern. It results from variants in the ATP7A gene on the X chromosome. Males (who have one X chromosome) are affected when that single copy is altered; females would need variants in both X chromosomes, which is rare. A characteristic of X‑linked inheritance is that fathers cannot pass X‑linked traits to their sons.

Other Names for This Condition

Dermatolysis
Dermatomegaly

Additional Information & Resources

Genetic Testing Information

Genetic Testing Registry: Cutis laxa with osteodystrophy
Genetic Testing Registry: Cutis laxa, autosomal dominant
Genetic Testing Registry: Cutis laxa, autosomal recessive
Genetic Testing Registry: Cutis laxa, X‑linked

Genetic and Rare Diseases Information Center

Cutis laxa
Occipital horn syndrome

Patient Support and Advocacy Resources

National Organization for Rare Disorders (NORD)

Clinical Trials

ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

CUTIS LAXA, AUTOSOMAL DOMINANT 1; ADCL1
CUTIS LAXA, AUTOSOMAL DOMINANT 2; ADCL2
CUTIS LAXA, AUTOSOMAL DOMINANT 3; ADCL3
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA; ARCL1A
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB; ARCL1B
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IC; ARCL1C
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA; ARCL2A
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIB; ARCL2B
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A
CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIB; ARCL3B
CUTIS LAXA, NEONATAL, WITH MARFANOID PHENOTYPE
OCCIPITAL HORN SYNDROME; OHS

Scientific Articles on PubMed

PubMed

References

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Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998 Jan-Feb;1(1):85-98. doi: 10.1007/s100249900011.
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Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. 2009 Mar 19 [updated 2023 Mar 16]. In: Adam MP, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.
Van Maldergem L, Loeys B. FBLN5-Related Cutis Laxa. 2009 Mar 19 [upda