Genetic syndromes associated with cutis laxa (CL) and wrinkled skin are multisystem disorders with progeroid features, including sagging, lax and wrinkled skin [1, 2]. Metabolic CL is genetically heterogeneous. We previously reported on the frequently overlapping clinical phenotypes, including X-linked and autosomal recessive forms [2]. However, recently new forms of CL have been described.

“Metabolic” CL is related to different inborn errors of metabolism; the historic example is the X-linked defect in ATP7A (MIM 309400). Autosomal recessive metabolic CL types are ARCL2 and ARCL3. ARCL2 patients present with a characteristic face, skeletal and joint abnormalities, developmental and growth delay due to mutations in different genes, including ATP6V0A2 (MIM 219200, 278250), RIN2 (MIM 613075), COG7(MIM 608779), GORAB (MIM 231070), and PYCR1 (MIM 612940, 614438) [2,3,4]. These encode endosomal and Golgi proteins (ARCL2A), and affect trafficking and glycosylation, except for PYCR1, which is involved in mitochondrial proline synthesis (ARCL2B). ARCL3 patients have parchment-like, progeroid skin, cataracts, corneal clouding, and significant neurologic disease [5], caused by mutations in PYCR1 or ALDH18A1 (MIM 616603, 219150), also involved in mitochondrial proline synthesis [2]. Additional inborn errors can also be associated with CL without a clear designation to ARCL2 or ARCL3; Transaldolase deficiency (TALDO MIM 606003) and Lenz-Majewski syndrome (MIM 151050) and Cantu syndrome (MIM 239850). ATP6V0A2-CDG related CL has been described both with normal elastin histology (wrinkly skin syndrome MIM 278250) and abnormal elastin histology (ARCL2A MIM 219200). COG7-CDG is another CDG with CL and normal elastin morphology.

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