First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation

Yumi Asakura, Koji Muroya, Takeshi Sato, Kenji Kurosawa, Gen Nishimura, Masanori Adachi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1982-1986
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number8
DOIs
Publication statusPublished - 2012 Aug
Externally publishedYes

Fingerprint

Mutation
Menarche
Oligomenorrhea
Delayed Puberty
Prognathism
Cryptorchidism
Hormone Replacement Therapy
Hearing Loss
Skull
Gonadotropin-Releasing Hormone
Growth mental deficiency syndrome of Myhre
Joints
Mothers
Phenotype
Polymerase Chain Reaction
Skin
Genes

Keywords

  • Gonadal dysfunction
  • Growth retardation
  • Muscular hypertrophy
  • Myhre syndrome
  • SMAD4
  • Thick calvarium

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation. / Asakura, Yumi; Muroya, Koji; Sato, Takeshi; Kurosawa, Kenji; Nishimura, Gen; Adachi, Masanori.

In: American Journal of Medical Genetics, Part A, Vol. 158 A, No. 8, 08.2012, p. 1982-1986.

Research output: Contribution to journalArticle

Asakura, Yumi ; Muroya, Koji ; Sato, Takeshi ; Kurosawa, Kenji ; Nishimura, Gen ; Adachi, Masanori. / First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation. In: American Journal of Medical Genetics, Part A. 2012 ; Vol. 158 A, No. 8. pp. 1982-1986.
@article{4761624a5f0a46dd8c8063f8783d95ed,
title = "First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation",
abstract = "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.",
keywords = "Gonadal dysfunction, Growth retardation, Muscular hypertrophy, Myhre syndrome, SMAD4, Thick calvarium",
author = "Yumi Asakura and Koji Muroya and Takeshi Sato and Kenji Kurosawa and Gen Nishimura and Masanori Adachi",
year = "2012",
month = "8",
doi = "10.1002/ajmg.a.35440",
language = "English",
volume = "158 A",
pages = "1982--1986",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - First case of a Japanese girl with Myhre syndrome due to a heterozygous SMAD4 mutation

AU - Asakura, Yumi

AU - Muroya, Koji

AU - Sato, Takeshi

AU - Kurosawa, Kenji

AU - Nishimura, Gen

AU - Adachi, Masanori

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - Gonadal dysfunction

KW - Growth retardation

KW - Muscular hypertrophy

KW - Myhre syndrome

KW - SMAD4

KW - Thick calvarium

UR - http://www.scopus.com/inward/record.url?scp=84864137952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864137952&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.35440

DO - 10.1002/ajmg.a.35440

M3 - Article

C2 - 22711472

AN - SCOPUS:84864137952

VL - 158 A

SP - 1982

EP - 1986

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 8

ER -