Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
권호 표지

A Case of Smith-Lemli-Opitz Syndrome in DHCR7 Mutation

DHCR 7 유전자 돌연변이로 확진된 스미스-렘리-오피츠 증후군 1례

  • Jeong, Yu Ju (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Huh, Rimm (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwun, Younghee (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Jieun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Sung Yoon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ki, Chang-Seok (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin, Dong-Kyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 정유주 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 허림 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 권영희 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 이지은 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 조성윤 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 기창석 (성균관대학교 의과대학 삼성서울병원 진단검사의학과) ;
  • 진동규 (성균관대학교 의과대학 삼성서울병원 소아청소년과)
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disease caused by a defect in cholesterol biosynthesis. This mutation encodes 7-dehydrocholesterol reductase (DHCR7), which is located on chromosome 11q13. It is characterized by typical facial appearances, microcephaly, small up-turned nose, cleft palate, syndactyly, and is correlated with cardiac, gastrointestinal and genital malformations. There may also be mental retardation, behavioral problems and growth retardation. It causes a broad spectrum of effects, ranging from a mild disorder of learning and behavior to a lethal malformation. There are four reports of Smith-Lemli-Opitz syndrome in Korean children. Here, we describe a two months old female with microcephaly, toe syndactyly and a cleft soft palate who was diagnosed as SLOS with c. 1054 C>T (p.R352W) and c.907G>A (p. G303R) mutations.

스미스-렘리-오피츠 증후군은 상염색체 열성유전질환으로 콜레스테롤 합성의 장애로 나타나는 질병이다. 7-dehydrochlolesterol reductase 유전자의 변이로 인하여 콜레스테롤을 합성하지 못함으로써 정신지체, 자폐증, 발육부진, 내부장기 기형, 손과 발의 기형, 면역기능 저하, 소화기 및 시력의 문제 등이 나타난다. 이 질환은 경미한 증상에서부터 치명적인 증상까지 다양한 스펙트럼을 가진다. 저자들은 다양한 기형을 가진 환아에서 조기에 스미스-렘리-오피츠 증후군을 유전자 분석을 통하여 진단하였으며, 조기 진단 후 식이진행 및 기형에 대한 치료, 콜레스테롤을 보충 하였으며, 이를 문헌고찰과 함께 보고하는 바이다.

Keywords

References

  1. Tsukahara M, Fujisawa K, Yamamoto K, Hasui M, Saito C, Yamamaka T, et al. Smith-Lemli-Opitz syndrome in Japan. Am J Med Genet 1998;75:118-9. https://doi.org/10.1002/(SICI)1096-8628(19980106)75:1<118::AID-AJMG24>3.0.CO;2-O
  2. Kelley RI. RSH/Smith-Lemli-Opitz syndrome: mutations and metabolic morphogenesis. Am J Hum Genet 1998;63:322-6. https://doi.org/10.1086/301987
  3. Ko JS, Choi BS, Seo JK, Shin JY, Chae JH, Kang GH, et al. A novel DHCR7 mutation in a Smith-Lemli-Opitz syndrome infant presenting with neonatal cholestasis. J Korean Med Sci 2010;25:159-62. https://doi.org/10.3346/jkms.2010.25.1.159
  4. Jong Hee C, Ki Joong K, Yong Seung H, Ki CS, Kim JW. Identification of a novel DHCR7 mutation in a Korean patient with Smith-Lemli-Opitz syndrome. J Child Neurol 2007;22:1297-300. https://doi.org/10.1177/0883073807307099
  5. Lee HJ. The Smith-Lemli-Opitz syndrome with a G303R/R352W mutation: in an extremly irritable child responsive to cholesterol supplementation Genes & Genomics 2010;32:9-12. https://doi.org/10.1007/s13258-010-0687-0
  6. Park MR, Ko JM, Cheon CK, Kim GH, Yoo HW. A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene. Korean J Pediatr 2008;51:1236-40. https://doi.org/10.3345/kjp.2008.51.11.1236
  7. Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994;330:107-13. https://doi.org/10.1056/NEJM199401133300205
  8. Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet 2012;160C:250-62. https://doi.org/10.1002/ajmg.c.31343
  9. Waterham HR, Hennekam RC. Mutational spectrum of Smith-Lemli-Opitz syndrome. Am J Med Genet C Semin Med Genet 2012;160C:263-84. https://doi.org/10.1002/ajmg.c.31346
  10. Fitzky BU, Witsch-Baumgartner M, Erdel M, Lee JN, Paik YK, Glossmann H, et al. Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci U S A 1998;95:8181-6. https://doi.org/10.1073/pnas.95.14.8181
  11. Svoboda MD, Christie JM, Eroglu Y, Freeman KA, Steiner RD. Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders. Am J Med Genet C Semin Med Genet 2012;160C:285-94. https://doi.org/10.1002/ajmg.c.31347
  12. Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet 1997;68:305-10. https://doi.org/10.1002/(SICI)1096-8628(19970131)68:3<305::AID-AJMG11>3.0.CO;2-X
  13. Haas D, Garbade SF, Vohwinkel C, Muschol N, Trefz FK, Penzien JM, et al. Effects of cholesterol and simvastatin treatment in patients with Smith- Lemli-Opitz syndrome (SLOS). J Inherit Metab Dis 2007;30:375-87. https://doi.org/10.1007/s10545-007-0537-7
  14. Jira PE, Wevers RA, de Jong J, Rubio-Gozalbo E, Janssen-Zijlstra FS, van Heyst AF, et al. Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome. J Lipid Res 2000;41:1339-46.
  15. Haas D, Haege G, Hoffmann GF, Burgard P. Prenatal presentation and diagnostic evaluation of suspected Smith-Lemli-Opitz (RSH) syndrome. Am J Med Genet A 2013;161A:1008-11.
  16. Johnson VP. Smith-Lemli-Opitz syndrome: review and report of two affected siblings. Z Kinderheilkd 1975;119:221-34. https://doi.org/10.1007/BF00443506
  17. Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet 2000;37:321-35. https://doi.org/10.1136/jmg.37.5.321