Cutis laxa, autosomal dominant Q82.8

Cutis laxa is the name given to a heterogeneous group of hereditary diseases whose main symptom is a pendulous, inelastic (in contrast to Marfan's syndrome and Ehlers-Danlos syndrome) skin. These cutaneous characteristics are almost always due to loss, fragmentation or severe disorganisation of the elastic fibres. The systemic significance of this disorder of elastogenesis affects different organ systems. Besides the skin, lungs and vessels are mainly affected. The hereditary forms of Cutis laxa are triggered by mutations in various genes (e.g. PYCR1, LTBP4, ATP6V0A2; elastin gene , etc.) which are functionally involved in the build-up or breakdown or in the organisation of elastic fibres. Basically, autosomal dominant forms can be distinguished from autosomal recessive forms, independent of the gene systematics. If the clinical phenomenon "cutis laxa" or rather "cutis laxa-like skin changes" is considered in terms of differential diagnosis, further hereditary as well as acquired clinical pictures have to be taken into account.

Prevalence: <1 / 1 000 000; about 50 cases have been described worldwide.

Autosomal dominant cutis laxa (ADCL) is caused by mutations in the elastin gene (ELN gene, gene location 7q11.23), a gene that codes for elastin. Most patients have a frameshift mutation in one of the last five exons of the ELN gene (ADCL1, OMIM: 123700). In one patient, a tandem duplication in the FBLN5 gene (ADCL2, OMIM: 614434) was described (Duz MB et al. 2017)

Newborn, infancy;

The clinical spectrum of autosomal dominant cutis laxa is essentially limited to the skin. Organ involvement is much less pronounced in terms of severity than in the autosomal recessive forms.

In addition to the signs of cutis laxa (progeroid aspect of children), pulmonary emphysema and aortic aneurysm are found. However, involvement of internal organs is usually rare and less severe than in the autosomal recessive forms of cutis laxa. Possible associated symptoms include:

Hernias, abnormalities of the heart valves (redundant mitral and tricuspid valves), cardiovascular manifestations(pulmonary stenosis, dilated and tortuous arteries and aorta), gastrointestinal diverticula and emphysema (Szabo Z et al 2006).

There is no specific therapy for cutis laxa, only symptomatic measures for accompanying disorders are possible.

Homozygous FBLN5 mutations are associated with autosomal recessive type 1 cutis laxa syndrome (ARCL1), which is characterized by a severe form of progression.

1. Duz MB et al (2017) A novel case of autosomal dominant cutis laxa in a consanguineous family: report and literature review. Clin Dysmorphol 26:142-147.
2. Okuneva EG et al (2019) A novel elastin gene frameshift mutation in a Russian family with cutis laxa: a case report. BMC Dermatol 19:4.
3. Szabo Z et al (2006) Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet 43:255-258.
4. Vodo D et al (2015) Autosomal dominant cutis laxa resulting from an intronic mutation in ELN. Exp Dermatol 24:885-887.
5. Xiao H et al (2019) Analysis of ELN gene mutation in a pedigree affected with cutis laxa. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 36:785-788.