분자 유전학적 방법으로 진단된 선천성 근육긴장성 이영양증 환자의 임상 양상 = Clinical characteristics of congenital myotonic dystrophy diagnosed by molecular genetic method

다국어 초록 (Multilingual Abstract)

Purpose : We performed this study to investigate the perinatal and developmental features of the patients with congenital myotonic dystrophy (CDM) confirmed by the molecular genetic method and the clinical characteristics of their mother, and to identify the relation between the number of CTG repeats and the clinical severity.
Methods : A retrospective review of the medical records and the results of the dystrophia myotonica protein kinase (DMPK) gene test was done for the patients who were confirmed as CDM through gene analysis from January 2001 to September 2006.
Results : All of the eight patients (male 2, female 6) showed moderate to severe degree of perinatal distress and feeding difficulty associated with profound hypotonia. Three patients had the history of polyhydramnios and two patients had equinovarus deformity. The developmental milestones were delayed in all patients, which improved gradually with age. All of their mothers demonstrated myotonic symptoms and typical myopathic face. The number of CTG repeats in DMPK gene analysis ranged 1,000-2,083, and there was no significant correlation between the number of CTG repeats and the time of walking alone.
Conclusion : All patients with CDM presented with severe hypotonia in perinatal period, and developmental delay thereafter, which were improved with age. All of their mothers manifested myotonic symptoms with typical myopathic face, and the identification of such features greatly contributed to the diagnosis of the patients. The number of CTG repeats had no significant influence on the motor development.

국문 초록 (Abstract)

목 적 : 선천성 근육긴장성 이영양증(congenital myotonic dystrophy, CDM) 환자의 주산기 병력, 영아기 및 소아기의 증상, 그리고 환자 어머니의 임상양상을 확인하여, 임상진단에 도움이 될 수 있는 특징적인 소견과, DMPK유전자의 CTG 서열반복 수와 운동발달 관계를 확인하고자 하였다.
방 법 : 2001년 1월부터 2006년 9월까지 삼성서울병원에서 DMPK 유전자 검사를 통해 CDM으로 확진된 환자 8명(남자 2명, 여자 8명)을 대상으로 의무기록과 DMPK 유전자 검사를 후향적으로 분석하였다.
결 과 : 진단 시 환자들의 연령은 7일에서 45개월(중앙값: 20.5 개월)이었으며, 환자들은 발달지연, 수유곤란, 그리고 근육긴장저하를 주소로 내원하였다. 3명의 환자에서 산전 초음파 상 원인 불명의 양수과다증이 확인되었다. 모든 환자에서 운동발달지연이 있었으며, 연령이 증가할수록 호전되었다. 모든 환자들의 어머니에서 전형적인 근병증의 모습과 근육긴장증을 확인하였고, 4명의 환자에서는 어머니 형제의 가족력을 확인하였다. DMPK유전자의 CTG 서열반복 수는 1,000-2,083(중앙값: 1,533.5)의 분포를 보였으며, 운동발달 중 혼자 걷기의 지연 정도와 유의한 상관관계는 없었다. 1명의 환자에서 세대간 예견효과를 확인하였다.
결 론 : CDM 환자는 산전초음파에서 양수과다증, 내반첨족, 태동의 저하 등의 소견을 보이고, 출생 후 근육긴장저하와 연관된 호흡곤란, 수유곤란, 그리고 발달지연 등의 증상을 나타낸다. 모든 환자들의 어머니는 특징적인 근병증의 외양과 근육긴장증을 가지고 있어, 산모에 대해 이러한 소견을 확인하는 것이 산전진단에 중요한 단서가 된다. CDM에서 근육긴장저하와 연관된 증상은 연령이 증가할수록 호전되며, DMPK 유전자의 CTG 서열반복 수와 운동발달 중 혼자 걷기 시기 간의 유의한 연관은 없었다.

참고문헌 (Reference)

1 New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1)., "The International Myotonic Dystrophy Consortium (IDMC)" 54 : 1218-1221, 2000

2 Harley HG, "Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy" 52 : 1164-1174, 1993

3 Pearson CE, "Repeat instability: mechanisms of dynamic mutations" 6 : 729-742, 2005

4 Day JW, "RNA pathogenesis of the myotonic dystrophies" 15 : 5-16, 2005

5 Roig M, "Presentation, clinical course, and outcome of the congenital form of myotonic dystrophy" 11 : 208-213, 1994

6 Geifman-Holtzman O, "Prenatal diagnosis of congenital myotonic dystrophy and counseling of the pregnant mother: case report and literature review" 78 : 250-253, 1998

7 Martorell L, "Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families" 27 : 68-72, 2007

8 Rudnik-Schoneborn S, "Outcome in pregnancies complicated by myotonic dystrophy: a study of 31 patients and review of the literature" 114 : 44-53, 2004

9 Imbert G, "Origin of the expansion mutation in myotonic dystrophy" 4 : 72-76, 1993

10 Zerylnick C, "Normal variation at the myotonic dystrophy locus in global human populations" 56 : 123-130, 1995

11 Lavedan C, "Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism" 52 : 875-883, 1993

12 Cho DH, "Myotonic dystrophy: Emerging mechanisms for DM1 and DM2" 1772 : 195-204, 2006

13 Harper PS, "Myotonic dystrophy, In Myology" McGraw Hill Professional 1039-1076, 2004

14 Mahadevan M, "Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene" 255 : 1253-1255, 1992

15 Schara U, "Myotonic dystrophies type 1 and 2: a summary on current aspects" 13 : 71-79, 2006

16 Harper PS, "Myotonic Dystrophy" W.B. Saunders 13-78, 1989

17 Lueck JD, "Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy" 129 : 79-94, 2007

18 Dubowitz V, "Muscle Disorders in Childhood" WB Saunders Co 289-, 1995

19 Brook JD, "Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member" 69 : 385-, 1992

20 Dubowitz V, "Genetic counselling" 2 : 85-86, 1992

21 Groenen P, "Expanding complexity in myotonic dystrophy" 20 : 901-912, 1998

22 Zaki M, "Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome" 29 : 284-288, 2007

23 Arsenault ME, "Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions" 66 : 1248-1250, 2006

24 Machuca-Tzili L, "Clinical and molecular aspects of the myotonic dystrophies: a review" 32 : 1-18, 2005

25 Furling D, "Changes in myotonic dystrophy protein kinase levels and muscle development in congenital myotonic dystrophy" 162 : 1001-1009, 2003

26 Jung SH, "Belated diagnosis of congenital myotonic dystrophy in a boy with cerebral palsy" 86 : 161-165, 2007

27 Fu YH, "An unstable triplet repeat in a gene related to myotonic muscular dystrophy" 255 : 1256-1258, 1992

28 Kim SH, "A Case of Congenital Myotonic Dystrophy Diagnosed by Molecular Genetics" 13 : 194-198, 2006

29 Kim HK, "A Case of Congenital Myotonic Dystrophy Diagnosed by Molecular Genetics" 356-360, 1998