Pathogenesis, Epidemiology, Diagnosis and Clinical Aspects of Smith-Lemli-Opitz Syndrome.
BACKGROUND
Smith-Lemli-Opitz Syndrome (SLOS) is a malformation syndrome inherited in an autosomal recessive fashion. It is due to a metabolic defect in the conversion of 7-dehydrocholesterol to cholesterol, which leads to an accumulation of 7-dehydrocholesterol and frequently a deficiency of cholesterol. The syndrome is characterized by typical dysmorphic facial features, multiple malformations, and intellectual disability.


METHODS
In this paper we provide an overview of the clinical phenotype and discuss how the manifestations of the syndrome vary depending on the age of the patients. We then explore the underlying biochemical defect and pathophysiological alterations that may contribute to the many disease manifestations. Subsequently we explore the epidemiology and succinctly discuss population genetics as they relate to SLOS. The next section presents the diagnostic possibilities. Thereafter, the treatment and management as is standard of care are presented.


CONCLUSIONS
Even though the knowledge of the underlying molecular mutations and the biochemical alterations is being rapidly accumulated, there is currently no efficacious therapy addressing neurological dysfunction. We discuss the difficulty of treating this disorder, which manifests as a combination of a malformation syndrome and an inborn error of metabolism. A very important factor in developing new therapies is the need to rigorously establish efficacy in controlled trials.
National Institute of Child Health and Human Development, Program in Developmental Endocrinology and Genetics, Section on Molecular Dysmorphology, 10 Center Drive, Bld 10 Rm 9D42, Bethesda, MD 20892, .
Simona E
SE
Bianconi
National Institute of Child Health and Human Development, Program in Developmental Endocrinology and Genetics, Section on Molecular Dysmorphology, 10 Center Drive, Bld 10 CRC, Rm 1-3288, Bethesda, MD 20892.
Joanna L
JL
Cross
National Institute of Child Health and Human Development, Program in Developmental Endocrinology and Genetics, Section on Molecular Dysmorphology, 10 Center Drive, Bld 10 CRC, Rm 1-3288, Bethesda, MD 20892.
Christopher A
CA
Wassif
National Institute of Child Health and Human Development, Program in Developmental Endocrinology and Genetics, Section on Molecular Dysmorphology, 10 Center Drive, Bld 10, CRC, Rm 2571, Bethesda, MD 20892, .
Forbes D
FD
Porter