De Novo Autosomal Dominant Cutis Laxa Type 3 With Global Developmental Delay and Musculoskeletal Features of Refractory Rickets

Cutis laxa is a genetically heterogeneous disorder characterized primarily by loose, redundant skin with abnormal wrinkling and elasticity. It is an exceptionally rare condition, with an estimated prevalence of < 1 in 1,000,000 individuals. In addition to the distinctive cutaneous manifestations, cutis laxa can present with a constellation of other features, including progeroid appearance, growth retardation, and developmental delays. We report a case of a 26-month-old girl who presented with features similar to nutritional rickets with global developmental delay and some additional features of joint and skin hyper-laxity in the backdrop of severely low vitamin D levels. The patient, however, failed to respond to the conventional treatment for rickets. Subsequent genetic testing revealed an autosomal dominant form of cutis laxa caused by an exceedingly rare c.377G>A (p.Arg126His) substitution in the ALDH18A1 gene, which encodes the bifunctional enzyme catalyzing the final steps of de novo phospholipid biosynthesis. The present case highlights the diagnostic challenges posed by cutis laxa, as the clinical manifestations can overlap with other conditions, leading to potential misdiagnosis or delayed recognition. The rarity of this disorder, combined with its phenotypic variability, underscores the importance of raising awareness among clinicians and expanding the literature to encompass the full spectrum of presentations associated with cutis laxa.