Smith‐Lemli‐Opitz syndrome — Fetal phenotypes with special reference to the syndrome‐specific internal malformation pattern

Autor: Franco Laccone, Martina Witsch-Baumgartner, Matthias Meyer‐Wittkopf, Helga Rehder, Johannes Zschocke, Barbara Fritz, Robert Petrovic, Annette Ramaswamy, Ralf Schmitz, Jana Behunova, Katharina Schoner, Britta Kluge, Susanne Gerit Kircher, Rainer Bald
Rok vydání: 2019
Předmět:
0301 basic medicine
Oxidoreductases Acting on CH-CH Group Donors
congenital
hereditary
and neonatal diseases and abnormalities
Embryology
Microcephaly
Pathology
medicine.medical_specialty
Health
Toxicology and Mutagenesis
Mutation
Missense
Autopsy
030105 genetics & heredity
Toxicology
fetal Smith‐Lemli‐Opitz syndrome
03 medical and health sciences
Fetus
Holoprosencephaly
Pregnancy
Humans
Medicine
Missense mutation
Abnormalities
Multiple
Cyst
atrioventricular septal defect
Research Articles
DHCR7 gene mutations
business.industry
Heart Septal Defects
bilateral renal agenesis
medicine.disease
Smith-Lemli-Opitz Syndrome
Bilateral Renal Agenesis
Phenotype
holoprosencephaly
030104 developmental biology
Smith–Lemli–Opitz syndrome
Polysyndactyly
Mutation
Pediatrics
Perinatology and Child Health
Female
Dandy-Walker Syndrome
business
Research Article
Developmental Biology
Zdroj: Birth Defects Research
ISSN: 2472-1727
Popis: Background Autosomal‐recessive SLOS is caused by mutations in the DHCR7 gene. It is defined as a highly variable complex of microcephaly with intellectual disability, characteristic facies, hypospadias, and polysyndactyly. Syndrome diagnosis is often missed at prenatal ultrasound and fetal autopsy Methods We performed autopsies and DHCR7 gene analyses in eight fetuses suspected of having SLOS and measured cholesterol values in long‐term formalin‐fixed tissues of an additional museum exhibit Results Five of the nine fetuses presented classical features of SLOS, including four cases with atrial/atrioventricular septal defects and renal anomalies, and one with additional bilateral renal agenesis and a Dandy‐Walker cyst. These cases allowed for diagnosis at autopsy and subsequent SLOS diagnosis in two siblings. Two fetuses were mildly affected and two fetuses showed additional holoprosencephaly. These four cases and the exhibit had escaped diagnosis at autopsy. The case with bilateral renal agenesis presented a novel combination of a null allele and a putative C‐terminus missense mutation in the DHCR7 gene Conclusions In view of the discrepancy between the prevalence of SLOS among newborns and the carrier frequency of a heterozygous DHCR7 gene mutation, the syndrome‐specific internal malformation pattern may be helpful not to miss SLOS diagnosis in fetuses at prenatal ultrasound and fetal autopsy
Databáze: OpenAIRE
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