Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features

Cold Spring Harb Mol Case Stud. 2018 Oct 1;4(5):a003046. doi: 10.1101/mcs.a003046. Print 2018 Oct.


Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent.

Keywords: congenital thrombocytopenia; exocrine pancreatic insufficiency; hepatic bridging fibrosis; hypercalciuria; intellectual disability, mild; portal fibrosis; short stature; spondylometaphyseal dysplasia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Bone Marrow Diseases / diagnosis
  • Bone Marrow Diseases / genetics*
  • Exocrine Pancreatic Insufficiency / diagnosis
  • Exocrine Pancreatic Insufficiency / genetics*
  • Exome Sequencing
  • Female
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / physiology*
  • Genetic Variation / genetics
  • Humans
  • Lipomatosis / diagnosis
  • Lipomatosis / genetics*
  • Mutation
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / physiopathology
  • Peptide Elongation Factors
  • Phenotype
  • Proteins / genetics
  • Ribonucleoprotein, U5 Small Nuclear
  • Shwachman-Diamond Syndrome


  • EFL1 protein, human
  • Peptide Elongation Factors
  • Proteins
  • Ribonucleoprotein, U5 Small Nuclear
  • SBDS protein, human
  • GTP Phosphohydrolases

Supplementary concepts

  • Pyle disease