Cutis laxa, autosomal recessive, type 1c Q82.8

Cutis laxa is the name given to a heterogeneous group of hereditary diseases characterized by a pendulous, inelastic (in contrast to Marfan's syndrome and Ehlers-Danlos syndrome) skin. These cutaneous and systemic features are almost always due to loss, fragmentation or severe disorganisation of the dermal elastic fibres. The hereditary forms of cutis laxa are caused by mutations in genes which are functionally involved in the build-up or breakdown of elastic fibres. In principle, autosomal dominant forms can be distinguished from autosomal recessive forms, independent of the gene system. If the clinical phenomenon "cutis laxa" or better "cutis-laxa-like skin changes" is considered from a differential diagnostic point of view, further hereditary as well as acquired clinical pictures have to be considered.

The clinical spectrum of autosomal recessive cutis laxa is very heterogeneous with respect to organ involvement and severity. Cutis laxa, autosomal recessive, type 1C is caused by a mutation in the LTBP4 gene (latent transforming growth factor-beta-binding protein 4) (gene location 19q13.2), which codes for the protein of the same name - latent transforming growth factor-beta-binding protein.

Mutations of the LTBP4 gene play a pathogenetically important role in Duchenne muscular dystrophy (DMD) (Van Dorn CS et al. 2018).

Clinically, in addition to a pronounced cutis laxa, severe life-threatening functional disorders of the lungs are seen due to cystic and atelectatic changes complicated by tracheomalacia and diaphragmatic hernias (Urban Z et al. 2009).

Cardiovascular changes tend to be mild.

Gastrointestinal changes: diverticulosis, tortuosity and stenosis.

Genitourinary tract: Hydronephrosis of the kidneys

Skeletal system: Joint laxity and decreased muscle tone lead to musculoskeletal problems. Craniofacial features: Microretrognathia, flat midface, receding forehead and wide fontanelles.

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3. Loeys B et al (2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet 11:2113-2118.
4. Papke CL et al (2015) Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.Hum Mol Genet 24:5867-5879.https://www.ncbi.nlm.nih.gov/pubmed/?term=Cutis+laxa%2C+autosomal+recessive%2C+type+1A
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