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GENATLAS PHENOTYPE
last update : 24-01-2018
Symbol AFND
Location 5q12.1
Name acromelic frontonasal dysostosis
Corresponding gene ZSWIM6
Main clinical features
  • association of skeletal abnormalities and severe-to-profound mental retardation, agenesis of the nasal root, marked separation of slitlike nares, tibial aplasia, hallucal polydactyly, and varus deformity
  • frontonasal malformation of the face and nasal clefting associated with striking symmetric preaxial polysyndactyly of the feet and variable tibial hypoplasia, large anterior fontanel with an interfrontal bone, and posterior parietal foramina and interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability
  • neurological features with low truncal tone, delayed motor milestones in the first year of life, and delayed onset of walking, frequent feeding difficulties, failure to thrive, or gastro-esophageal reflux
    • Genetic determination autosomal dominant
    Related entries including cases with severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations (PMID: 29198722)
    Function/system disorder mental retardation
    osteo-articular
    neurology
    Type disease
    Remark(s)
    Genotype/Phenotype correlations
  • recurrent de novo nonsense variant c.2737C>T, that may result in a dominant-negative effect due to production of a truncated ZSWIM6 protein that lacks the Sin-3-like domain should be considered causal of a severe-profound ID , that lack the characteristic facial clefting, significant hypertelorism, interhemispheric lipomas, and limb anomalies of the AFND (PMID: 29198722))
  • AFND, is caused by the recurrent p.Arg1163Trp variant within the C-terminal Sin3-like domain that may result in a gain of function (PMID: 29198722))