Sjögren-Larsson syndrome: technique and timing of prenatal diagnosis.

Background: Sjögren-Larsson syndrome is an autosomal recessive disease with sequelae including ichthyosis, mental retardation, and spasticity. Although fetal skin biopsy has permitted prenatal diagnosis of Sjögren-Larsson syndrome in the late second trimester, it is accompanied by substantial risks, including fetal loss, premature labor, and detection at a gestational age close to the legal limit for pregnancy termination in most states. A new technique involving biochemical assay of cultured amniocytes for reduced levels of fatty alcohol:oxidized nicotinamide-adenine dinucleotide (NAD+)-oxidoreductase may allow earlier and less invasive detection of Sjögren-Larsson syndrome.

Case: A 38-year-old Lebanese woman, gravida 6, para 3, presented for prenatal diagnosis of Sjögren-Larsson syndrome following a history of two children born with the disease. At 19 weeks' gestation, multiple fetal skin biopsies were obtained by ultrasound-guided transabdominal percutaneous insertion of biopsy forceps. Histologic examination of the specimen revealed no evidence of Sjögren-Larsson syndrome. However, assay of fatty alcohol:NAD(+)-oxidoreductase in cultured amniocytes obtained at fetal skin biopsy showed a profound enzymatic deficiency. Additional fetal skin biopsies were obtained at 23.5 weeks' gestation, and histologic examination was positive for Sjögren-Larsson syndrome. The patient elected to terminate the pregnancy, and a subsequent autopsy on the fetus confirmed Sjögren-Larsson syndrome.

Conclusion: This case demonstrates the limitations of histologic examination of fetal skin specimens for the diagnosis of Sjögren-Larsson syndrome and indicates the potential value of biochemical detection from fetal amniocytes. This new technique may allow earlier diagnosis of Sjögren-Larsson syndrome, is less invasive, and may be less psychologically traumatic for the patient if she elects to terminate the pregnancy.