Smith-Lemli-Opitz syndrome
Encyclopedia
Smith-Lemli-Opitz syndrome (also SLOS, or 7-dehydrocholesterol reductase deficiency) is an autosomal
recessive metabolic and developmental congenital disorder
that causes the inability to correctly produce or synthesize cholesterol due to a low occurrence of the 7-DHC reductace enzyme.
SLOS is also linked to autism
Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 40,000 births. It is most common in Caucasians (especially Scandinavians) of European ancestry, but very rare among African and Asian populations.
This disorder is inherited in an autosomal recessive pattern, which means two copies of the gene
must be inherited to have the disorder. It is estimated that as many as 1 in 30 people are carriers for the syndrome.
Mutations in the DHCR7 gene
cause Smith-Lemli-Opitz syndrome. The DHCR7 gene makes an enzyme
called 7-dehydrocholesterol reductase
. This enzyme is responsible for the final step in the production of cholesterol
. Cholesterol is an essential nutrient that is necessary for normal embryonic
development. Cholesterol is also a structural component of cell membrane
s and the protective substance covering nerve cells (myelin
). Additionally, cholesterol plays an important role in the production of certain hormone
s and digestive acids.
Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol
reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome.
. Studies have shown up to 86% of children with SLOS also had autism.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive metabolic and developmental congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
that causes the inability to correctly produce or synthesize cholesterol due to a low occurrence of the 7-DHC reductace enzyme.
Symptoms
The signs and symptoms of SLOS syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual and physical disabilities. Common symptoms are:- Small head size (microcephalyMicrocephalyMicrocephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
) - Mental retardationMental retardationMental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
- Learning disabilities and behavioral problems
- Malformations of the heartHeartThe heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, lungLungThe lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s, kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, gastrointestinal tractGastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, and genitalia - HypocholesterolemiaHypocholesterolemiaHypocholesterolemia is the presence of abnormally low levels of cholesterol in the blood . Although the presence of high cholesterol has been linked strongly with cardiovascular disease, a defect in the body's production of cholesterol can lead to adverse consequences as well...
- Paleness
- Low muscle tone (hypotoniaHypotoniaHypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
) - Delayed development and speech
- Feeding difficulties
- Drooping eyelids (ptosisPtosisPtosis refers to droopiness of a body part. Specifically, it can refer to:* Ptosis * Ptosis * Enteroptosis * Gastroptosis...
) - Cataracts
- Hirschsprung disease
- Hearing impairment
- Weak immune system
- ScoliosisScoliosisScoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
- OsteoporosisOsteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
- Fused second and third toes (syndactylySyndactylySyndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
) - Extra fingers or toes (polydactylyPolydactylyPolydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
)
SLOS is also linked to autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
Genetic prevalence
This disorder is inherited in an autosomal recessive pattern, which means two copies of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
must be inherited to have the disorder. It is estimated that as many as 1 in 30 people are carriers for the syndrome.
Mutations in the DHCR7 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
cause Smith-Lemli-Opitz syndrome. The DHCR7 gene makes an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
called 7-dehydrocholesterol reductase
7-dehydrocholesterol reductase
7-dehydrocholesterol reductase, also known as DHCR7, is a protein in humans which is encoded by the DHCR7 gene.-Function:The protein encoded by this gene is an enzyme catalyzing the production of cholesterol from 7-Dehydrocholesterol using NADPH....
. This enzyme is responsible for the final step in the production of cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Cholesterol is an essential nutrient that is necessary for normal embryonic
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
development. Cholesterol is also a structural component of cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s and the protective substance covering nerve cells (myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
). Additionally, cholesterol plays an important role in the production of certain hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s and digestive acids.
Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol
7-Dehydrocholesterol
7-Dehydrocholesterol is a zoosterol that functions in the serum as a cholesterol precursor, and is converted to vitamin D3 in the skin, therefore functioning as provitamin-D3. The presence of this compound in human skin enables humans to manufacture vitamin D3 from ultra-violet rays in the sun...
reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome.
Autism
SLOS is believed to have a relation to autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. Studies have shown up to 86% of children with SLOS also had autism.