Cutis laxa, autosomal recessive, type 2b 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.

Present is a mutation at the PYCR1 gene (pyrroline-5-carboxylate reductase 1 - gene location 17q25.3), a protein-coding gene encoding an enzyme of the same name localized in the mitochodria that catalyzes the NAD (P) H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiological role in the generation of NADP (+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants.

The clinical spectrum of autosomal recessive cutis laxa is very heterogeneous with respect to organ involvement and severity. Autosomal recessive cutis laxa, type 2B is characterized by clinical prognathism, elongated face, osteopenia, and cutis laxa on the back of the hand and foot. Pulmonary emphysema, common in other cutis laxa variants, is absent. Patients with PYCR1 mutations are usually severely mentally disabled (Yildirim Y et al. 2010).

There is a large phenotypic correspondence with Geroderma osteodysplasticum, which is based on an autosomal recessive mutation in the GORAB gene.

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4. Yildirim Y et al (2010) The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2 at J Med Genet A 155A:134-140. https://www.ncbi.nlm.nih.gov/pubmed/21204221