Smith-Lemli-Opitz Syndrome – Causes, Symptoms & Treatment

Smith-Lemli-Opitz Syndrome

Smith- Lemli -Opitz syndrome is a congenital malformation syndrome. The cause is one of a total of 70 gene mutations on chromosome 11q13.4. The disease is inherited in an autosomal recessive manner and is an extremely rare disease with multiple organ malformations and impaired cholesterol biosynthesis.

What is Smith-Lemli-Opitz Syndrome?

Smith-Lemli-Opitz syndrome falls into the group of autosomal recessive hereditary malformation syndromes . A gene mutation causes a metabolic disorder in the biosynthesis of cholesterol in the disease . The syndrome is the most common congenital disorder of cholesterol biosynthesis. The prevalence of the disease in Europe is between about 1:60,000 and 1:10,000.

This means that the disease can be classified as a rare disease, although it is one of the most common congenital ones in cholesterol biosynthesis. On the continents of Asia and Africa, the syndrome is even more rare. The disease was first described in 1964. At that time, the geneticists DW Smith, L. Lemli and J. Marius Opitz documented the symptom complex from a scientific point of view. Since then, just over 300 cases have been reported.

Boys are affected more often than girls. The symptoms are probably less pronounced in girls and therefore more difficult to diagnose. The disease is congenital, but develops progressively from birth and is therefore characterized by different courses. The syndrome is divided into types I and II depending on the symptoms.


Smith-Lemli-Opitz syndrome is caused by a gene mutation that was pinpointed in 1998. Chromosome 11q13.4 is now considered the location of the mutation , with more than 70 different mutations in this location being known to date. The type of causative mutation determines the severity and type of symptoms in the individual case. The gene in question is the 7-sterol reductase gene. S. Tint and his colleagues discovered that the syndrome does not allow the body to produce cholesterol.

This production involves the conversion of the precursor 7-dehydrocholesterol into endogenous cholesterol, which cannot function due to an enzyme defect resulting from the mutation. There is therefore an excess of 7-dehydrocholesterol in the organism of those affected. At the same time there is a general deficit of cholesterol. Because of the autosomal recessive inheritance of the syndrome, both parents must carry the defective gene and this is the only way they can pass it on to a child. With a 25 percent probability, the following children of parents with a sick child are also affected by the malformation syndrome.

Symptoms, Ailments & Signs

Children with Smith-Lemli-Opitz syndrome are born with typical craniofacial malformations, primarily microcephaly , a prominent forehead and a small nose with a broad nasal bridge. Microgenia is present along with an anteverted nares. A cleft palate and clouding of the lens are also often observed, especially cataracts and cataracts .

There is also blepharoptosis. Mentally and cerebrally, misdevelopments occur over the course of the disease, which result in mental disabilities . Holoprosencephaly and irritability can also characterize the clinical picture. In addition to self-injurious behavior, the syndrome can produce autistic behavior . In addition, there are multiple organ malformations, especially those of the heart and the urogenital tract.

Hypospadias and cryptorchidism are the most common urogenital malformations. Syndactyly of the toes may be present in addition to supernumerary fingers or toes . Muscle hypotonia , dysphagia and gastroesophageal reflux are also relevant in the context of the symptom complex . Intestinal dysmotility and pyloric stenosis are also common. In type II of the syndrome there is pseudo-hermaphroditism, in which the external genitalia are female, although a male body type predominates.

Diagnosis & disease progression

Ultrasound examinations can be used as prenatal diagnostics before birth to record the typical physical characteristics of Smith-Lemli-Opitz syndrome. In addition to growth retardation, a heart defect or the absence of a kidney can also be noticed. When examining the amniotic fluid , the mutation analysis may already provide a diagnosis-securing result.

After birth, the children have a characteristic face shape and special positions of the extremities, so that the suspected diagnosis can be made by visual diagnosis if the prenatal diagnosis has failed. The genetic diagnosis secures the suspicion. Smith-Lemli-Opitz syndrome is to be differentiated from fetal alcohol syndrome , Pallister-Hall syndrome, Kaufmann-McKusick syndrome and Cornelia de Lange syndrome .

The Patau syndrome , the ATR-X syndrome and the C syndrome , the Zellweger syndrome and the hydrolethalus syndrome must also be considered in the differential diagnosis. The same applies to orofacial digital syndrome, holoprosencephaly polydactyly syndrome and Meckel syndrome. The life expectancy of the children depends on the cholesterol concentration and the treatability of the organ malformations. Low cholesterol levels and severe malformations make an early fatal course likely. Children with high cholesterol and easily treatable malformations do not have a severely impaired life expectancy.


Due to the Smith-Lemli-Opitz syndrome, those affected suffer from various malformations and malformations. These have a very negative effect on the quality of life of the patient. The internal organs in particular are affected by the malformations, so that death can often occur immediately after birth. Furthermore, most patients suffer from a cleft palate and also from eye problems.

Furthermore, this syndrome often leads to mental disabilities and thus to mental retardation. Most patients are therefore dependent on the help of other people in their lives and can no longer cope with many everyday things on their own. The heart is also affected by the malformations, so that sudden cardiac death can occur. Furthermore, the Smith-Lemli-Opitz syndrome also affects the genitals, so that malformations can also occur in these.

Smith-Lemli-Opitz syndrome can usually only be treated symptomatically. There are no complications and some of the symptoms can be reduced. However, a completely positive course of the disease cannot be achieved. Whether life expectancy will be restricted cannot be universally predicted.

Treatment & Therapy

Lifelong social and medical care is often unavoidable for patients with Smith-Lemli-Opitz syndrome. Their development is usually severely delayed in terms of cognitive and motor skills. In almost all cases, this results in a lifelong disability that does not permit an independent lifestyle. Therefore, supportive treatment is the main priority.

As part of these measures, the parents receive psychotherapeutic support and ideally learn how to deal with their child’s illness. The Smith-Lemli-Opitz syndrome cannot be cured and therefore cannot be treated causally. However, since a disorder of cholesterol metabolism has been documented for the syndrome, symptomatic treatment to compensate for the cholesterol deficiency is possible. This treatment is done by administering cholesterol.

The usually numerous malformations of the organs have to be corrected surgically, as far as this is within the realm of possibility. An exception to this is the frequently documented multi-joint structure of the fingers and toes, which does not necessarily require surgical intervention. Accompanying symptoms such as visual difficulties can also be easily treated and alleviated today.

The majority of those affected suffer from nutritional problems such as sucking and swallowing difficulties or gastroesophageal reflux and disturbed gastrointestinal peristalsis. Therefore, a nasogastric tube must often be used to ensure safe food intake. Behavioral problems can sometimes be treated in behavioral therapy.


After a positive prenatal diagnosis of Smith-Lemli-Opitz syndrome, parents are given the opportunity to terminate the pregnancy. Otherwise, the Smith-Lemli-Opitz syndrome can only be prevented if couples have molecular genetic diagnostics carried out during family planning and, after proof of the mutation has been provided, decide not to have children.


The aftercare measures for Smith-Lemli-Opitz syndrome (SLOS) are based on the severity of the symptoms that occur during the course of the disease. In the majority of cases, the children have nutritional problems. They thrive badly. The primary focus of aftercare is therefore adequate nutrition for the affected children by means of high-calorie liquid food fed through the nasogastric route and the administration of sufficient cholesterol.

The further course of the disease also shows that the affected children often show underdevelopment of the brain. This underdevelopment usually leads to a physical or mental disability with varying degrees of severity. For example, not all affected children learn to walk. In this case, to compensate for the restricted mobility, aids for everyday movement (e.g. wheelchair, walking and standing aids) are provided as aftercare measures.

In the case of mental symptoms such as autoaggression and hyperactivity, the therapeutically prescribed drug treatment is continued as a follow-up measure. In addition, around 50 percent of all affected children develop a moderate to severe heart defect as the disease progresses. After the operation on the heart defect, electrocardiographic (ECG) and sonographic examinations are planned at regular intervals.

Psychological consultations and therapies are recommended for the parents of children with SLOS. Independent living in adulthood is rather unlikely. When it comes to aftercare for SLOS, extensive care measures are to be expected in adulthood. In addition, life expectancy can be limited by organ malformations.

You can do that yourself

The disease is associated with numerous complaints that severely limit the quality of life. If a member of the family has been diagnosed with the genetic disease, a doctor should be consulted before procreating offspring. Possible risks should be weighed up so that prudent decisions can be made for all parties involved. During pregnancy, you must also take part in all check-ups that are offered.

As soon as the health impairments of the child are noticed, parents and relatives can take appropriate precautions and better prepare for future developments. In a large number of cases, the care and support of a patient with Smith-Lemli-Opitz syndrome poses an enormous challenge for the relatives. Therefore, they should know and respect their physical and emotional limits. It is advisable to examine whether medical care can be used for the patient and, at the same time, psychotherapeutic support for the relatives. This can often lead to improvements in dealing with the disease.

It must be taken into account that a stable social environment is important for the patient. In addition, you should always keep calm in everyday life when adversities and challenges arise. Since the person concerned is not able to lead an independent life for the rest of his life, there should be special empathy when dealing with him.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.