Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome

Am J Med Genet A. 2018 May;176(5):1212-1215. doi: 10.1002/ajmg.a.38666.


The SETD2-related overgrowth syndrome is also called "Luscan-Lumish syndrome" (OMIM 616831) with the clinical characteristics of intellectual disability, speech delay, macrocephaly, facial dysmorphism, and autism spectrum disorders. We report on two novel patients a 4.5-year-old boy and a 23-year-old female adolescent with a speech and language developmental delay, autism spectrum disorder and macrocephaly, who were both diagnosed with SETD2-related overgrowth syndrome due to de novo frameshift mutations in the SETD2 gene. Features not previously described which were present in either one of our patients were nasal polyps, a large tongue with creases, a high pain threshold, constipation, and undescended testicles. These features may be related to the syndrome and may need special attention in future patients. Additionally, prevention of obesity should be an important point of attention for patients diagnosed with a SETD2-related overgrowth syndrome.

Keywords: Luscan-Lumish syndrome; OMIM 616831; SETD2; Sotos-like syndrome; autism; obesity; overgrowth.

Publication types

  • Case Reports

MeSH terms

  • Autism Spectrum Disorder / diagnosis*
  • Autism Spectrum Disorder / genetics*
  • Child, Preschool
  • DNA Copy Number Variations
  • Facies
  • Female
  • Frameshift Mutation
  • Genetic Association Studies
  • Heterozygote
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Megalencephaly / diagnosis*
  • Megalencephaly / genetics*
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Syndrome
  • Young Adult


  • Histone-Lysine N-Methyltransferase
  • SETD2 protein, human