Maternally inherited MAF variant associated with variable expression of Aymé-Gripp syndrome

Am J Med Genet A. 2019 Nov;179(11):2233-2236. doi: 10.1002/ajmg.a.61299. Epub 2019 Aug 7.


Aymé-Gripp syndrome is an intellectual disability syndrome characterized by autism spectrum disorder, cataracts, sensorineural hearing loss, skeletal involvement, seizures, cardiac anomalies, and distinctive facial features. The condition is caused by pathogenic variants in MAF. To date, less than 20 cases have been reported, the majority having de novo mutations. Here, we report a patient with classical features of Aymé-Gripp syndrome who inherited a MAF variant, c.206C>G (p.P69R), from a mother with normal intellectual function and normal hearing but with cataract and significant proteinuria. To the best of our knowledge, this is the first report of a patient who inherited a MAF causative variant from a parent with normal intellect. Although the syndrome typically has multiple malformations and intellectual disability, we suggest that a mild phenotype could exist. In addition, we suggest that the basal ganglia calcifications present in our proband could be a novel finding associated with MAF variants and offer further support for the relationship between these variants and late manifestations of renal disease.

Keywords: Aymé-Gripp syndrome; MAF; cataract; hearing loss; intellectual disability; variable expressivity.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Brain / abnormalities
  • Brain / diagnostic imaging
  • Gene Expression Regulation*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Maternal Inheritance*
  • Phenotype
  • Proto-Oncogene Proteins c-maf / genetics*
  • Syndrome


  • MAF protein, human
  • Proto-Oncogene Proteins c-maf