Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene

7-dehydrocholesterol reductase (DHCR7) 변이로 진단된 Smith-Lemli-Opitz 증후군 1예

  • Park, Mee Rim (Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Ko, Jung Min (Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Cheon, Chong-Keun (Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Clinic and Laboratory, Asan Medical Center, University of Ulsan, College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine)
  • 박미림 (울산의대 서울아산병원 소아청소년과) ;
  • 고정민 (울산의대 서울아산병원 소아청소년과) ;
  • 전종근 (울산의대 서울아산병원 소아청소년과) ;
  • 김구환 (울산의대 서울아산병원 의학유전학클리닉) ;
  • 유한욱 (울산의대 서울아산병원 소아청소년과)
  • Received : 2008.06.12
  • Accepted : 2008.09.10
  • Published : 2008.11.15
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Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.

Smith-Lemli-Opitz 증후군은 콜레스테롤 합성 과정의 장애로 발생하는 상염색체 열성으로 유전되는 드문 질환으로 다양한 기형을 동반한다. 이는 DHCR7 유전자 변이로 인한 활성도 저하로 발생하는 질환으로 7DHC, 8DHC의 증가 및 체내 콜레스테롤의 감소에 따른 임상상을 특징으로 한다. 저자들은 국내에서 최초로 SLO 증후군을 유전자 분석을 통하여 진단하였기에 이를 문헌 고찰과 함께 보고하는 바이다.

Keywords

References

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