Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica

Int J Mol Sci. 2017 Mar 15;18(3):635. doi: 10.3390/ijms18030635.


Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient's clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.

Keywords: ATPase, H+ transporting lysosomal V0 subunit A2 (ATP6V0A2); GOLGIN, RAB6-INTERACTING (GORAB); Pyrroline-5-carboxylate reductase 1 (PYCR1); autosomal recessive cutis laxa 2A; autosomal recessive cutis laxa 2B; geroderma osteodysplastica.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Bone Diseases / congenital*
  • Bone Diseases / diagnosis
  • Child
  • Child, Preschool
  • Cutis Laxa / diagnosis*
  • Diagnosis, Differential
  • Dwarfism / diagnosis*
  • Female
  • Humans
  • Infant
  • Male
  • Phenotype*
  • Skin Diseases, Genetic / diagnosis*
  • Syndrome

Supplementary concepts

  • Cutis Laxa, Autosomal Recessive, Type IIA
  • Cutis Laxa, Autosomal Recessive, Type IIB
  • Gerodermia osteodysplastica