Cutis laxa, autosomal dominant

Other Names: ADCL; 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.

Cause

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

Inheritance

Autosomal dominant pattern, a 50/50 chance.

When cutis laxa is caused by ELN mutations, it has an autosomal dominant inheritance pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Rarely, cases of cutis laxa resulting from FBLN5 mutations can also have an autosomal dominant pattern of inheritance.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Premature skin wrinkling
• Redundant skin(Loose redundant skin)

30%-79% of people have these symptoms

• Bowel diverticulosis
• Full cheeks(Apple cheeks)
• Hypertelorism(Wide-set eyes)
• Joint hyperflexibility(Joints move beyond expected range of motion)

5%-29% of people have these symptoms

• Abnormal heart valve morphology
• Aortic aneurysm(Bulge in wall of large artery that carries blood away from heart)
• Emphysema
• Inguinal hernia
• Pulmonic stenosis(Narrowing of pulmonic valve)
• Umbilical hernia

Diagnosis

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.

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.

NIH genetic and rare disease info

• NIH info on Cutis laxa, autosomal dominant

Cutis laxa, autosomal dominant is a rare disease.