Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2

Am J Med Genet A. 2014 Feb;164A(2):484-9. doi: 10.1002/ajmg.a.36277. Epub 2013 Oct 29.


The disorder comprising Macrocephaly, Alopecia, Cutis laxa, and Scoliosis has been designated MACS syndrome. It is a rare condition, inherited in an autosomal recessive pattern. Three families from different ethnic origins have so far been reported and were all linked to homozygous mutations in RIN2, a gene encoding the Ras and Rab interactor 2 protein involved in cell trafficking. We describe herein the fourth family with MACS syndrome in two siblings carrying a novel homozygous mutation, c.1878_1879insC in exon 8 of the RIN2 gene, which predicts p.Ile627Hisfs*7. We also report on additional findings not previously described in MACS syndrome, including bronchiectasis and hypergonadotropic hypogonadism. Finally, our overall data support the argument that RIN2 syndrome is a more appropriate name for the disorder.

Keywords: Ehlers-Danlos-like syndromes; MACS/RIN2 syndrome; RIN2; cutis laxa-like syndromes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Alopecia / diagnosis*
  • Alopecia / genetics*
  • Carrier Proteins / genetics*
  • Cutis Laxa / diagnosis*
  • Cutis Laxa / genetics*
  • DNA Mutational Analysis
  • Facies
  • Female
  • Gene Order
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Male
  • Megalencephaly / diagnosis*
  • Megalencephaly / genetics*
  • Mutation*
  • Pedigree
  • Phenotype
  • Scoliosis / diagnosis*
  • Scoliosis / genetics*
  • Siblings*
  • Syndrome
  • Young Adult


  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • RIN2 protein, human

Supplementary concepts

  • Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis