Loss-of-Function Variants in EFEMP1 Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations

Genes (Basel). 2021 Mar 31;12(4):510. doi: 10.3390/genes12040510.


Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in EFEMP1. Hence, we identified EFEMP1 as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT.

Keywords: EFEMP1; FBLN3; cutis laxa; diaphragmatic hernia; elastic fiber; extracellular matrix; fibulin-3; inguinal hernia.

Publication types

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

MeSH terms

  • Child
  • Consanguinity
  • Cutis Laxa / genetics*
  • Diagnosis, Differential
  • Exome Sequencing
  • Extracellular Matrix Proteins / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Loss of Function Mutation*
  • Male
  • Pedigree


  • EFEMP1 protein, human
  • Extracellular Matrix Proteins