title: Don't miss patients with atypical FMR1 mutations: dysmorphism and clinical features in a boy with a partially methylated FMR1 full mutation.
abstract: Fragile X syndrome characterized by intellectual disability (ID), facial dysmorphism, and postpubertal macroorchidism is the most common monogenic cause of ID. It is typically induced by an expansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene on Xq27 to more than 200 repeats. Only rarely patients have atypical mutations in the FMR1 gene such as point mutations, deletions, or unmethylated/partially methylated full mutations. Most of these patients show a minor phenotype or even appear clinically healthy. Here, we report the dysmorphism and clinical features of a 17-year-old boy with a partially methylated full mutation of approximately 250 repeats. Diagnosis was made subsequently to the evaluation of a FMR1 premutation as the cause for maternal premature ovarian failure. Dysmorphic evaluation revealed no strikingly long face, no prominent forehead/frontal bossing, no prominent mandible, no macroorchidism, and a head circumference in the lower normal range. Acquisition of a driving license for mopeds and unaccompanied rides by public transport in his home province indicate rather mild ID (IQ = 58).
  
  
  CONCLUSIONS
  This adolescent demonstrates that apart from only minor ID, patients with a partially methylated FMR1 full mutation present less to absent pathognomonic facial dysmorphism, thus emphasizing the impact of family history for a straightforward clinical diagnosis.
authors.affiliation: Clinical Department of Pediatrics I, Innsbruck Medical University, Innsbruck, Austria, edda.haberlandt@uki.ac.at.
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Sibylle
authors.initials: S
authors.lastname: Zotter
authors.forename: Martina
authors.initials: M
authors.lastname: Witsch-Baumgartner
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D019175:DNA Methylation; D005145:Face / Q000002:abnormalities*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000097:blood / Q000235:genetics*; D005600:Fragile X Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D015415:Biomarkers; D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human