Cutis Laxa Type 2E Report of a New Case Highlighting Hypotonia as a Major Feature

Cutis laxa syndrome type 2E (CL2E) is a very rare disorder caused by pathogenic variants in the latent transforming binding growth factor β1 (LTBP1) gene. LTBP1 truncating variants may induce a defective binding of LTBP1 to the extracellular matrix components (ECM) and dysregulate the transforming growth factor β (TGFβ) signalling. CL2E patients share some common features to all cutis laxa syndromes. However, they are characterised by short stature and skeletal abnormalities. Here we report a new patient with a novel homozygous c.3731-1G>A variant in the LTBP1 gene. Congenital hypotonia was the first symptom. The clinical features of our patient were compared to the eight patients previously reported in the literature. A transmission electronic microscopy (TEM) on proband-derived dermal fibroblasts was performed to improve the phenotype-genotype correlations. Our patient presents skin and joint hyperlaxity as others CL2E patients, but a late onset of a very mild cutis laxa appeared only since one year of age. He showed no short stature, no typical skeletal abnormalities such as brachydactyly, syndactyly or clinodactyly. Cardiac malformations, learning difficulties, or hearing loss were also absent. The phenotype seems milder compared to previous descriptions. However, the TEM analysis supports the pathogenicity of the variant because of a result compatible with a cutis laxa. In conclusion, our case extends the phenotype of CL2E and highlights a new phenotype considering hypotonia as the main clinical sign.