What is the mortality and morbidity associated with Smith-Lemli-Opitz syndrome (SLOS)?

Updated: Jan 27, 2021
  • Author: Robert D Steiner, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Answer

Spontaneous abortion of fetuses with Smith-Lemli-Opitz syndrome is not unusual. Stillbirths have also been reported, although a prospective study by Gibbins et al found that homozygous DHCR7 mutations (indicative of Smith-Lemli-Opitz syndrome) were present in only one out of 139 unexplained stillbirths (0.7%), suggesting that unrecognized DHCR7 mutations are not strongly associated with stillbirth. [15]

A study by Daum et al indicated that homozygosity for the founder variant DHCR7:c.964-1G>C, carried in the Ashkenazi Jewish population and other populations, is associated with severe phenotype for Smith-Lemli-Opitz syndrome, including early miscarriage in some cases, and a very high rate of early postnatal mortality. [16]

Death from multiorgan system failure during the first weeks of life is typical in the most severely affected individuals with Smith-Lemli-Opitz syndrome. Cause of death can include pneumonia, lethal congenital heart defect, or hepatic failure. Survival is unlikely if the plasma cholesterol level is less than approximately 20 mg/dL as measured by gas chromatography, which is used because routine methods of cholesterol measurement include precursor sterols.

Congenital heart disease is not uncommon in Smith-Lemli-Opitz syndrome and can cause cyanosis or congestive heart failure. Pulmonary hypertension has been noted in at least one patient. [17] Vomiting, feeding difficulties, constipation, toxic megacolon, electrolyte disturbances, and failure to thrive are common and, in some cases, related to GI anomalies. Liver disease has been described in a subset of patients. [18] Visual loss may occur because of cataracts, optic nerve abnormalities, or other ophthalmologic problems, [19] and subclinical retinal abnormalities may be noted on electroretinography. [20] Cataracts may occur acutely in the postnatal period. [21] Hearing loss is fairly common.


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