Conflicts of interest: None.
Article first published online: 18 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 8, pages 1982–1986, August 2012
How to Cite
Asakura, Y., Muroya, K., Sato, T., Kurosawa, K., Nishimura, G. and Adachi, M. (2012), First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation. Am. J. Med. Genet., 158A: 1982–1986. doi: 10.1002/ajmg.a.35440
How to Cite this Article: Asakura Y, Muroya K, Sato T, Kurosawa K, Nishimura G, Adachi M. 2012. First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation. Am J Med Genet Part A. 158A:1982–1986.
- Issue published online: 19 JUL 2012
- Article first published online: 18 JUN 2012
- Manuscript Accepted: 1 APR 2012
- Manuscript Received: 7 MAR 2012
- Myhre syndrome;
- growth retardation;
- thick calvarium;
- muscular hypertrophy;
- gonadal dysfunction
This article reports the first case of a Japanese girl with molecularly confirmed Myhre syndrome (MS). The patient was 9 years old at her first visit, and she had been diagnosed with unknown skeletal dysplasia. Her phenotype fulfilled the clinical and radiological criteria for MS, such as typical facies with prognathism, hearing impairment, short stature, square body shape, and limited joint mobility. The thick calvarium and thick skin were clues to the clinical diagnosis of MS. A heterozygous mutation in the mothers-against-DPP homolog 4 (SMAD4) gene has been reported to cause MS. We sequenced SMAD4 using standard PCR-based technique and identified a recurrent mutation (p.Ile500 Thr). She attained menarche before 11 years of age; however, she developed oligomenorrhea after a few years of 40-day cycles, necessitating hormone replacement therapy. The luteinizing hormone-releasing hormone (LHRH) tests suggested abnormalities related to hypothalamo-hypophyseal malfunction. Previous reports on MS described early menarche in girls and early or delayed puberty and cryptorchidism in boys. Therefore, we recommend performing an endocrinological evaluation of the hypothalamo-hypophyseal-gonadal axis in patients with MS to clarify whether hormonal abnormalities are associated with the syndrome. © 2012 Wiley Periodicals, Inc.