Cutis laxa is a disorder characterized by loose, redundant, wrinkled, sagging, and hypoelastic skin. When the skin is stretched, it returns to its former shape very slowly. Diagnosis is based on clinical manifestation, skin biopsy, and genetic testing. There is no specific treatment, but plastic surgery is sometimes performed.
Cutis laxa may be inherited or acquired (1).
Hereditary forms of cutis laxa are autosomal dominant, autosomal recessive, or X-linked and have wide phenotypic variation. In addition to lax skin, clinical features include joint deformities, several musculoskeletal problems, and several systemic (cardiovascular, respiratory, gastrointestinal, neurological) symptoms. Some autosomal recessive forms that are associated with the FBLN5, FBLN4, EFEMP2, LTBP4, PYCR1, ATP6V0A2, and ALDH18A1 genes and some autosomal dominant and X-linked forms can cause life-threatening complications such as arterial stenosis or tortuosity/aneurysm and early-onset emphysema. Phenotypically related but genetically distinct disorders, such as geroderma osteodysplasticum and arterial tortuosity syndrome, have significant overlap with cutis laxa.
Acquired forms of cutis laxa occur in response to an inflammatory or environmental insult; however, the underlying susceptibility is not well understood.
General reference
1. Beyens A, Boel A, Symoens S, Callewaert B. Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology. Clin Genet. 2021;99(1):53-66. doi:10.1111/cge.13865
Pathophysiology of Cutis Laxa
Cutis laxa, which can be hereditary or acquired, is caused by abnormal elastin metabolism that results in fragmented elastin and thus reduced elasticity of the skin. Copper deficiency, elastin quantity and morphology, and elastases and elastase inhibitors, are implicated in the abnormal elastin degradation (1, 2).
Hereditary cutis laxa is caused by a variety of autosomal dominant, autosomal recessive, and X-linked recessive mutations in genes involved in elastin synthesis, extracellular matrix proteins, and copper metabolism. cutis laxa is caused by a variety of autosomal dominant, autosomal recessive, and X-linked recessive mutations in genes involved in elastin synthesis, extracellular matrix proteins, and copper metabolism.
Acquired cutis laxa may develop after exposure to environmental factors including medications (hypersensitivity reactions), infections, hematologic problems, and inflammatory diseases. There are 2 types of acquired cutis laxa (3). Type 1 occurs mostly in adults but can also occur at any age. This type may be widespread or localized to a specific part of the body with or without systemic involvement. Type 2 is localized and occurs after acute inflammatory skin lesions.
Pathophysiology references
1. Beyens A, Boel A, Symoens S, Callewaert B. Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology. Clin Genet. 2021;99(1):53-66. doi:10.1111/cge.13865
2. Berk DR, Bentley DD, Bayliss SJ, Lind A, Urban Z. Cutis laxa: a review. J Am Acad Dermatol. 2012;66(5). doi:10.1016/j.jaad.2011.01.004
3. Peralta-Amaro AL, Quintal-Ramírez MJ, Esteban-Prado A, Chávez-Sánchez IN, Vera-Lastra OL, López-Velasco A, Acosta-Jiménez E, Cano-Viveros MI. Type I acquired cutis laxa: Report of a unique progressive case and short review. Am J Med Sci. 2024 Apr;367(4):268-273. doi: 10.1016/j.amjms.2024.01.015
Symptoms and Signs of Cutis Laxa
The classic skin symptom in cutis laxa is loose, redundant, wrinkled, sagging, and hypoelastic skin that slowly recoils after stretching.
In hereditary forms, dermal laxity may be present at birth or develop later; it occurs wherever the skin is normally loose and hanging in folds, most obviously on the face. Affected children have mournful or Churchillian facies and a hooked nose. The benign autosomal recessive form (type 2) also causes intellectual disability, joint laxity, gastrointestinal tract hernias, and diverticula.
Other features of the disorder depend on type and include congenital hip dislocations, scoliosis, osteopenia and fractures, growth restriction, brain malformation and movement disorder, arterial stenoses and tortuosity, cerebral aneurysms, and cataracts. If the disorder is severe, progressive pulmonary emphysema may precipitate cor pulmonale. Bronchiectasis, heart failure, and aortic aneurysms can also occur.
In acquired forms, affected people develop classic skin symptoms and may also develop systemic symptoms such as vascular abnormalities, intestinal diverticula, emphysema, and hernias.
This photo shows loose skin folds in a child with cutis laxa.
Diagnosis of Cutis Laxa
Clinical evaluation
Skin biopsy
Testing for systemic complications
Genetic testing
Diagnosis of cutis laxa is clinical. There are no specific laboratory findings; however, a skin biopsy may reveal abnormalities in elastic fibers.
Tests for associated systemic complications depend on the specific genotype/phenotype combination and may include echocardiography, magnetic resonance (MR) angiography, pulmonary function testing, high-resolution lung CT, cystography and abdominal ultrasound, spine and hip radiography, and brain MRI (1).
Genetic testing, in conjunction with clinical genetics evaluation and genetic counseling, is indicated for patients with early-onset cutis laxa or a suggestive family history because test results may predict the risk of transmission to offspring and the risk of extracutaneous organ involvement. Hereditary cutis laxa may not have complete penetrance.
Typical cutis laxa can be distinguished from Ehlers-Danlos syndromes because dermal fragility and articular hypermobility are absent. Other disorders sometimes cause localized areas of loose skin. In Turner syndrome, lax skinfolds at the base of an affected girl’s neck tighten and resemble webbing as she ages. In neurofibromatosis, unilateral pendular plexiform neuromas occasionally develop, but their configuration and texture distinguish them from cutis laxa.
Diagnosis reference
1. Beyens A, Boel A, Symoens S, Callewaert B. Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology. Clin Genet. 2021;99(1):53-66. doi:10.1111/cge.13865
Treatment of Cutis Laxa
Skin care
Tobacco avoidance
Sometimes physical therapy
Sometimes plastic surgery
There is no specific treatment for cutis laxa. Skin care such as sunscreen and moisturizer application is important as is tobacco avoidance.
Physical therapy may sometimes help increase skin tone and manage hypermobility.
Plastic surgery may considerably improve appearance in patients with hereditary cutis laxa but can be less successful in those with acquired cutis laxa (1).
Extracutaneous complications are treated appropriately with medications or surgery.
Positive pressure ventilation should be avoided when possible (2).
Treatment references
1. Katsuren K, Kuba R, Kasai S, Shimizu Y. Acquired Cutis Laxa on the Upper Eyelids and Earlobes: A Case Report and Literature Review. Arch Plast Surg. 2022;49(3):418-422. Published 2022 May 27. doi:10.1055/s-0042-1748657
2. Beyens A, Boel A, Symoens S, Callewaert B. Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology. Clin Genet. 2021;99(1):53-66. doi:10.1111/cge.13865
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