Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders

Am J Med Genet A. 2016 Sep;170(9):2310-21. doi: 10.1002/ajmg.a.37831. Epub 2016 Jul 4.


Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc.

Keywords: DGCR2; Marden-Walker syndrome; NCAM2; Van den Ende-Gupta syndrome; arachnodactyly; contracture; intellectual disability.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / metabolism
  • Arachnodactyly / diagnosis*
  • Arachnodactyly / genetics*
  • Arachnodactyly / metabolism
  • Blepharophimosis / diagnosis*
  • Blepharophimosis / genetics*
  • Blepharophimosis / metabolism
  • Child
  • Contracture / diagnosis*
  • Contracture / genetics*
  • Contracture / metabolism
  • DNA Copy Number Variations
  • Exome
  • Frameshift Mutation
  • Genetic Association Studies*
  • High-Throughput Nucleotide Sequencing
  • Homozygote
  • Humans
  • Male
  • Multimodal Imaging
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Scavenger Receptors, Class F / genetics


  • SCARF2 protein, human
  • Scavenger Receptors, Class F

Supplementary concepts

  • Marden Walker like syndrome

Grants and funding