Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) also known as 7-dehydrocholesterol reductase deficiency is an inborn error of cholesterol synthesis. 

Epidemiology

The estimated incidence is at 1:20000-40000 live births. Prevalence may be greater in Nordic countries.

Clinical presentation

There are many which include:

• CNS
  • intellectual disability
  • hyperexcitability
  • microcephaly
  • hypotonia
  • holoprosencephaly
• craniofacial
  • blepharophimosis
  • epicanthus
  • micrognathia
  • low set ears
• limb
  • postaxial polydactyly
  • syndactyly: usually 2^nd and 3^rd toes
• congenital cardiac anomalies
• congenital urogenital anomalies
  • hypospadias
  • cryptorchidism
• intra-uterine growth restriction (IUGR)

Pathology

The condition often results from a mutation in the DHCR7 gene on chromosome 11q12-13 which reduces the activity of 7-dehydrocholesterol reductase. Rarely there may be a mutation in chromosome 7q32.1. There is then a lack of cholesterol production as well as a build-up of potentially toxic by-products of cholesterol production which accumulate in the blood and other tissues. It was traditionally classified into 2 types although they are not considered to represent the spectrum differing severity.

Genetics

It carries an autosomal recessive inheritance ⁵.

Associations

• Hirschsprung disease

Markers

• low maternal low estriol ⁴: although nonspecific

Radiographic features

Antenatal ultrasound

There may be increased nuchal translucency in 1^st trimester as an early feature ³. Antenatal ultrasound may also be able to detect some of the above clinical features.

Treatment and prognosis

The syndrome carries a poor prognosis with most infants not surviving soon after birth.