Smith-Lemli-Opitz syndrome

Cholesterol is not only a fat in food. The body makes most of it, and it is essential for development. It forms part of every cell membrane and of myelin, the covering of nerve cells, and it is needed to produce certain hormones and digestive acids. In SLOS the final step of cholesterol production fails because the enzyme 7-dehydrocholesterol reductase is deficient. Cholesterol falls and potentially toxic by-products accumulate in blood, nervous system and other tissues.

It is not completely understood how the combination of low cholesterol and accumulated by-products produces each specific feature, but the result is that growth and development of many body systems are disturbed from early pregnancy.

Because symptoms begin before birth, many babies are underweight and slow to grow after birth. Features can include a small, long and narrow head, a cleft palate, a horizontal crease across the palms and soles, webbing or fusion of the second and third toes, extra fingers or toes in some, and genital differences that are most frequent in males. Heart, lungs, liver, kidneys and bowel can be affected. Infants often have low muscle tone and feeding difficulties.

Learning difficulty ranges from mild to severe. Many children show features of autism, and behavioural problems are common. People with milder forms may have mainly learning and behaviour problems with only minor physical differences, while severe forms can be life-threatening and involve profound intellectual disability and major malformations.

• Feeding: feeding difficulties are common and severe ones may call for tube feeding.

• Skin: marked sensitivity to ultraviolet light from the sun and other sources.

• Growth: slow growth and weight gain are usual, and the specialist team monitors both.

SLOS can be suspected before birth when an ultrasound scan shows physical differences, or when there is a family history. Confirmation in pregnancy involves testing amniotic fluid and a sample of cells from the placenta. After birth the signs usually lead to suspicion, and special blood and urine tests confirm the diagnosis by measuring cholesterol and its precursors. Genetic testing of DHCR7 follows and is useful for relatives.

There is no cure. Treatment aims to relieve symptoms and support the person. Increasing the amount of cholesterol in the diet is the most common form of treatment, either by choosing foods high in cholesterol such as egg yolk, meat, fish and dairy, or using supplements, with a dietitian and specialist advising. If feeding problems are severe, tube feeding may help. Surgery may be needed to correct physical differences, and extra treatment may be needed if heart, lungs, liver or kidneys are involved.

Physiotherapy, speech and language therapy and educational support help development. Metabolic Support UK advises sunscreen formulated to protect against UVA, with a high SPF of about 50 and a high UVA rating of 4 to 5 stars, alongside covering skin and avoiding strong sun.

Behaviour difficulties deserve proper assessment rather than being put down to the diagnosis, and community paediatric and mental health teams can help.

SLOS is autosomal recessive. If both parents are carriers, each child has a one in four (25%) chance of inheriting it and a one in two chance of being a carrier. Occasionally, carriers have had mild symptoms. After diagnosis a genetic counsellor explains inheritance, testing for relatives and options for future pregnancies, such as testing during pregnancy.

Outlook depends heavily on severity. Mild forms may lead to adult life with learning and behavioural support, while the most severe forms can be life-limiting in infancy. Because organ involvement differs, a single lead paediatrician or metabolic physician usually coordinates care, with transition to adult services in the teenage years.

Call 999 for breathing difficulty, a seizure that does not stop, or a baby who is blue or unresponsive. Seek urgent advice for repeated vomiting with dehydration, signs of infection in a baby with feeding tubes, or severe sunburn blistering.