A Novel Heterozygous MAP2K1 Mutation in a Patient with Noonan Syndrome with Multiple Lentigines

作者：Nishi Eriko; Mizuno Seiji; Nanjo Yuka; Niihori Tetsuya; Fukushima Yoshimitsu; Matsubara Yoichi; Aoki Yoko; Kosho Tomoki^*

来源：American Journal of Medical Genetics, Part A, 2015, 167(2): 407-411.

DOI：10.1002/ajmg.a.36842

• Noonan syndrome with multiple lentigines (NSML)
• MAP2K1
• cardio-facio-cutaneous syndrome (CFCS)

Noonan syndrome with multiple lentigines (NSML), formerly referred to as LEOPARD syndrome, is a rare autosomal-dominant condition, characterized by multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, growth retardation, and sensorineural deafness. To date, PTPN11, RAF1, and BRAF have been reported to be causal for NSML. We report on a 13-year-old Japanese boy, who was diagnosed with NSML. He was found to have a novel heterozygous missense variant (c.305A>G; p.E102G) in MAP2K1, a gene mostly causal for cardio-facio-cutaneous syndrome (CFCS). He manifested fetal macrosomia, and showed hypotonia and poor sucking in the neonatal period. He had mild developmental delay, and multiple lentigines appearing at approximately age 3 years, as well as flexion deformity of knees bilaterally, subtle facial characteristics including ocular hypertelorism, sensorineural hearing loss, and precocious puberty. He lacked congenital heart defects or hypertrophic cardiomyopathy, frequently observed in patients with NSML, mostly caused by PTPN11 mutations. He also lacked congenital heart defects, characteristic facial features, or intellectual disability, frequently observed in those with CFCS caused by MAP2K1 or MAP2K2 mutations. This may be the first patient clinically diagnosed with NSML, caused by a mutation in MAP2K1.

• 出版日期2015-2