Cutis laxa

OVERVIEW: What every practitioner needs to know

Are you sure your patient has cutis laxa? What are the typical findings for this disease?

Cutis Laxa is a hereditary disorder of connective tissue typified by wrinkled, furrowed skin and multiple non-cutaneous manifestations.

Typical findings for Cutis Laxa:

1. Furrowed, wrinkled skin; pulmonary emphysema, vascular anomalies including arterial tortuosity and aneurysms, peripheral pulmonary stenosis, supravalvular aortic stenosis

2. Diverticuli of bladder, bowel; inguinal hernias, craniofacial involvement (midface hypoplasia, high-arched palate)

Different types of Cutis Laxa involve the different organ systems and manifestations listed above to varying degrees.

What other disease/condition shares some of these symptoms?

Occipital horn syndrome – also called X-linked cutis laxa:

Occipital horn syndrome is caused by mutations in the gene encoding the alpha peptide of the Cu(2+)-transporting ATPase. Bony abnormalities of the occiput are a common feature. Other clinical features include hyperelastic skin with easy bruising, varicosities, bladder diverticuli, hernias, hyperextensible joints and multiple skeletal anomalies. Mild intellectual impairment may be seen.

Gerodermia osteodysplastica:

An autosomal recessive disorder caused by mutations in the GORAB gene on chromosome 1p24.2. Clinical features include drooping, prematurely aged appearance of the facial skin and bone involvement including osteoporosis and lines similar to the growth rings observed in tree trunks. The skin is lax but not hyperextensible. Facial appearance may include malar hypoplasia and prognathic mandible.

De Barsy syndrome:

An autosomal recessive, caused by mutations in the ALDH18A1 gene. Also called cutis laxa with corneal clouding and mental retardation. Clinical features include cutis laxa with thin, translucent skin, sparse hair, hernias, developmental delay, seizures, hypotonia, corneal opacities, pectus excavatum, hyperextensible joints and a variety of skeletal manifestations including wormian bones, scoliosis, congenital hip dislocation, adducted thumbs and talipes equinovarus.

What caused this disease to develop at this time?

Autosomal dominant cutis laxa is caused by mutations in the Elastin (ELN) or Fibulin-5 (FBLN5) genes.

Autosomal recessive cutis laxa is caused by mutations in FBLN4, FBLN5, ATP6V0A2, PYCR1 or LTBP4.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Skin biopsy with orcein staining on parafin embedded samples.

Light microscopy – may appear normal or show mild fragmentation absent or sparce elastin fibers.

Electron microscopy shows sparse elastin fibers, accumulation of elastin globules.

Would imaging studies be helpful? If so, which ones?

Echocardiogram to look for valvular heart disease, particularly supravalvular aortic stenosis.

Chest x-ray to look for evidence of emphysema.

Renal ultrasound for hydronephrosis.

If clinically indicated: Barium enema (diverticuli, intestinal dilation, tortuosity); voiding cystourethrogram (bladder diverticuli); magnetic resonance angiogram (arterial tortuosity, aneurysms).

Confirming the diagnosis

Diagnosis begins with a clinical assessment and review of the family history. If autosomal dominant cutis laxa is suspected clinically, molecular testing (gene sequencing) is performed to look for mutations in FBLN5 or ELN. If autosomal recessive cutis laxa is suspected, molecular sequencing for FBLN5, FBLN4, LTBP4, ATP6V0A2, and PYCR1 may be sought.

If molecular sequencing is non-revealing (or if only a single mutant allele is found in the case of AR cutis laxa), testing for large deletions is performed.

If you are able to confirm that the patient has cutis laxa, what treatment should be initiated?

Cutis laxa – may require plastic surgery (face, abdomen). Avoid sun tanning.
Inguinal hernias – routine repair.
Pulmonary emphysema – symptomatic therapy. Avoid exposure to cigarette smoke.
Arterial abnormalities – no definitive treatment available. Monitor aortic and arterial aneurysms; surgical intervention as indicated.
Surveillance and appropriate treatment for urinary tract infections.

What are the adverse effects associated with each treatment option?

Treatment options are non-controversial and relatively low-risk, unless emphysema diminishes lung function and increases the likelihood of complications from anesthesia.

What are the possible outcomes of cutis laxa?

Death from cardiorespiratory failure as a result of emphysema is the most common outcome. There is wide variability in severity, but survival beyond the second decade is unusual in FBLN5-related cutis laxa.

What causes this disease and how frequent is it?

Prevalence at birth is 1:4,000,000 for all types of cutis laxa.

Inheritance may be autosomal dominant or autosomal recessive.

How do these pathogens/genes/exposures cause the disease?

All types of cutis laxa are characterized by alterations in the elastin fibers, regardless of the underlying molecular cause.

How can cutis laxa be prevented?

Prenatal diagnosis is an option for families in which mutation(s) have been identified.

Pre-implantation diagnosis may be offered to couples if the disease-causing mutations are known.

What is the evidence?

Loeys, B, DePaepe, A, Urban, Z. “EFEMP2-Related Cutis Laxa”. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). 1977-2011. ( A comprehensive presentation of disease characteristics, diagnosis, testing, management and genetic counseling for EFEMP2-related cutis laxa.)

“Online Mendelian Inheritance in Man, OMIM”. (OMIM provides a narrative discussion of the available literature on the various types of cutis laxa.)

Van Maldergem, L, Loeys, B. “FBLN5-Related Cutix Laxa”. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). 1997-2011. (A comprehensive presentation of disease characteristics, diagnosis, testing, management and genetic counseling for FBLN5–related cutis laxa.)

Van Maldergem, L, Dobyns, W, Kornak, W. “TP6V0A2-Related Cutis Laxa”. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). May 10, 2011. (A comprehensive presentation of disease characteristics, diagnosis, testing, management and genetic counseling for TP6V0A2-related cutis laxa.)

No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.

Jump to Section

Pediatrics