Autosomal Dominant Cutis Laxa

A rare connective tissue disorder characterized by wrinkled, redundant and sagging inelastic skin associated in some cases with internal organ involvement.

Epidemiology

The prevalence of ADCL is unknown but less than 50 cases have been reported in the literature so far.

Clinical description

Patients are usually diagnosed at birth or in early childhood due to the presence of excessive skin folds and loose, redundant skin. ADCL is considered to be a mild form of cutis laxa with limited systemic involvement although associated features may include hernias, cardiac valve anomalies (redundant mitral and tricuspid valves), cardiovascular manifestations (pulmonary stenosis and aortic and arterial dilatation and tortuosity), gastrointestinal diverticuli and emphysema.

Etiology

ADCL is genetically heterogeneous: mutations in the elastin gene (ELN; 7q11.1-q21.1) have been reported in some cases, whereas mutations in the gene encoding fibulin-5 (FBLN5; 14q31) have been identified in others. Homozygous mutations in the FBLN5 are associated with the more severe form of CL with extensive systemic involvement, autosomal recessive CL type 1 (ARCL1; see this term).

Diagnostic methods

Diagnosis is based on clinical examination, family history and pathognomonic histological findings (sparse, fragmented elastic fibers) on skin biopsies. Molecular testing may allow confirmation of the diagnosis.

Differential diagnosis

The differential diagnosis may include other forms of CL (ARC1 and ARCL2, and X-linked CL) and related syndromes (gerodermia osteodysplastica, wrinkly skin syndrome and De Barsy syndrome), together with the Ehlers-Danlos syndromes, Cantu syndrome and Costello syndrome (see these terms).

Genetic counseling

Genetic counseling should be provided to affected families and prenatal diagnosis may be feasible for families in which the disease-causing mutation has been identified.

Management and treatment

There is no specific treatment for cutis laxa. Management should include symptomatic treatment of any associated manifestations. ADCL is generally a mild cutaneous disease and internal organ involvement is rare.

Prognosis

Most patients have a good prognosis and life expectancy is usually normal.