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

Epidemiology

The estimated incidence is at 1:20,000-40,000 live births. Prevalence may be greater in Nordic countries.

Associations

• Hirschsprung disease

Clinical presentation

There are many symptoms and signs 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

• intrauterine 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 byproducts of cholesterol production which accumulate in the blood and other tissues. It was traditionally classified into two types although they are not considered to represent the spectrum differing severity.

Genetics

It carries an autosomal recessive inheritance ⁵.

Markers

• low maternal low estriol is non-specific ⁴

Radiographic features

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 long after birth.