Neurological findings in cutis laxa syndromes; Identification of a new cutis laxa gene

Cutis laxa is an acquired or inherited condition characterized by redundant, sagging and inelastic skin. The inherited form is heterogeneous condition with autosomal dominant, autosomal recessive and X-linked inheritance. Autosomal dominant cutis laxa is divided into three types, type I, II and III and the responsible genes are ELN, FBLN5 and ALDH18A1 respectively. An X-linked form of cutis laxa also called occipital horn is allelic to Menkes syndrome and caused by mutations in ATP7A gene. It is characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities. Mild neurological findings might be present in some patients. The autosomal recessive forms are divided into types IA, IB, IC, IIA, IIB, IIIA, and IIIB. The genes responsible for these types are FBLN4, FBLN5, LTBP4, ATP6V0, PYCR1, ALDH18A1 and PYCR1 respectively. Neurological findings are found mainly in the autosomal recessive forms of cutis laxa. The similarities and differences of each type are discussed. Intellectual disability and hypotonia are features found in types IIA, IIB, IIIA, IIIB. Microcephaly can be seen in type IIA, IIB and IIIA, IIIB. Athetoid movements and dystonia are a distinguishing factor for type IIB, IIIA, IIIB. MRI finding that is occasionally found in type IIA is cobblestone like dysgenesis and agenesis of corpus callosum in IIA, IIIA, IIIB. We also present data on a novel type of cutis laxa caused by mutations in the E subunit of the V-ATPase complex that affects intracellular trafficking and secretion of major extracellular matrix constituents.