TY - JOUR
T1 - Variability in clinical and neuropsychological features of individuals with MAP2K1 mutations
AU - Pierpont, Elizabeth I.
AU - Semrud-Clikeman, Margaret
AU - Pierpont, Mary Ella
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Mutations in MAP2K1, a gene expressed within the RAS-mitogen activated protein kinase (RAS/MAPK) pathway, are generally associated with the clinical phenotype of cardiofaciocutaneous syndrome. Here we describe two male patients (ages 16 and 20 years) with mutations in MAP2K1 and heterogeneous clinical presentations. Both young men had short stature, some facial features suggesting a RASopathy and minimal cardiac involvement. Detailed medical and neuropsychological findings are presented alongside a comprehensive review of features of patients with MAP2K1 mutations reported in the literature. Published studies have indicated that cognitive functioning of individuals with MAP2K1 mutations can range from severe intellectual disability to mildly below average. Neither of the individuals presented here had severe intellectual disability, and one had intellectual functioning within the average range. Neurodevelopmental concerns that were common among our two patients included fine motor difficulties, slow processing speed, reduced attention span, learning disabilities, and diminished energy/alertness. Taken together, our findings demonstrate that mutations in MAP2K1, which are frequently associated with neurological complications and intellectual disability, can be associated with a milder clinical and neurocognitive profile more typical of individuals with Noonan syndrome. Variability of expression may arise from a complex interplay between RAS/MAPK pathway genotype, epigenetics, medical and obstetric factors, and environmental influences.
AB - Mutations in MAP2K1, a gene expressed within the RAS-mitogen activated protein kinase (RAS/MAPK) pathway, are generally associated with the clinical phenotype of cardiofaciocutaneous syndrome. Here we describe two male patients (ages 16 and 20 years) with mutations in MAP2K1 and heterogeneous clinical presentations. Both young men had short stature, some facial features suggesting a RASopathy and minimal cardiac involvement. Detailed medical and neuropsychological findings are presented alongside a comprehensive review of features of patients with MAP2K1 mutations reported in the literature. Published studies have indicated that cognitive functioning of individuals with MAP2K1 mutations can range from severe intellectual disability to mildly below average. Neither of the individuals presented here had severe intellectual disability, and one had intellectual functioning within the average range. Neurodevelopmental concerns that were common among our two patients included fine motor difficulties, slow processing speed, reduced attention span, learning disabilities, and diminished energy/alertness. Taken together, our findings demonstrate that mutations in MAP2K1, which are frequently associated with neurological complications and intellectual disability, can be associated with a milder clinical and neurocognitive profile more typical of individuals with Noonan syndrome. Variability of expression may arise from a complex interplay between RAS/MAPK pathway genotype, epigenetics, medical and obstetric factors, and environmental influences.
KW - MAP2K1
KW - MEK1
KW - Noonan syndrome
KW - RASopathies
KW - behavior
KW - cardiofaciocutanous syndrome
KW - cognitive
KW - neuropsychological
KW - phenotype
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U2 - 10.1002/ajmg.a.38044
DO - 10.1002/ajmg.a.38044
M3 - Article
C2 - 27862862
AN - SCOPUS:84999780458
SN - 1552-4825
VL - 173
SP - 452
EP - 459
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 2
ER -