The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly.

• Keywords
• Lenz-Majewski syndrome, PTDSS1, cutis laxa, hyperostotic skeletal dysplasia,
• MeSH
• Alleles MeSH
• Cutis Laxa diagnosis   genetics   MeSH
• Child MeSH
• Adult MeSH
• Exons MeSH
• Facies MeSH
• Phenotype * MeSH
• Genetic Association Studies MeSH
• Genotype MeSH
• Hyperostosis diagnosis   genetics   MeSH
• Humans MeSH
• Mutation * MeSH
• Child, Preschool MeSH
• Radiography MeSH
• Nitrogenous Group Transferases genetics   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• phospholipid serine base exchange enzyme MeSH Browser
• Nitrogenous Group Transferases MeSH