UNLABELLED: 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). CONCLUSION: 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.
UNLABELLED: 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). CONCLUSION: 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: Mallikarjuna R Guruju; K Lavanya; B K Thelma; M Sujatha; V R OmSai; V Nagarathna; P Amarjyothi; A Jyothi; M P J S Anandaraj Journal: J Clin Neurosci Date: 2009-06-27 Impact factor: 1.961
Authors: D Wöhrle; U Salat; D Gläser; J Mücke; M Meisel-Stosiek; D Schindler; W Vogel; P Steinbach Journal: J Med Genet Date: 1998-02 Impact factor: 6.318
Authors: S A Merenstein; V Shyu; W E Sobesky; L Staley; E Berry-Kravis; D L Nelson; K A Lugenbeel; A K Taylor; B F Pennington; R J Hagerman Journal: J Am Acad Child Adolesc Psychiatry Date: 1994 Nov-Dec Impact factor: 8.829
Authors: Elliott H Sherr; David J Michelson; Michael I Shevell; John B Moeschler; Andrea L Gropman; Stephen Ashwal Journal: Ann Neurol Date: 2013-08 Impact factor: 11.274