Introduction:
Syndromes are characterized by a set of signs and symptoms interrelated to each other. Some of them are genetically inherited, while others are acquired during an individual's lifetime. The most common inherited syndrome is Down’s syndrome, caused due to the presence of an additional copy of chromosome 21 (trisomy 21). Syndromes are usually named after the person who first describes them. So far, around 2700 syndromes have been identified and classified based on their signs and symptoms. Although some syndromes commonly occur, several syndromes occur in extremely low frequencies.
What Is Opitz Syndrome?
Opitz syndrome is also known by the following names:
1. 7-dehydrocholesterol reductase deficiency.
2. DHCR7 abnormality.
3. RSH syndrome.
4. SLOS.
5. SLO syndrome.
Opitz syndrome is a rare autosomal recessive (inheriting one copy of the mutated gene from each parent) congenital disorder caused by defects in cholesterol synthesis. The syndrome affects various body parts. The main features of Opitz syndrome include a small head, impaired intelligence, learning difficulties, and autism. It also affects the behavior of a child, social communication, and interaction. In addition, the lungs, heart, kidney, gut, and genitalia are malformed. Children with Opitz syndrome also have weak muscles, fused toes, and extra fingers.
What Causes Opitz Syndrome?
The main problem in Opitz syndrome lies in cholesterol synthesis. Cholesterol is an organic molecule and a wax-like substance from foods like egg yolk, poultry, fish, dairy, etc. Cholesterol is the main structural component of cell membranes and plays vital functions before and after birth. It also helps synthesize various hormones, digestive enzymes and forms a protective covering in nerve cells.
The metabolism of cholesterol happens through a cascade of events, and an enzyme called 7-dehydrocholesterol reductase plays a crucial role in cholesterol production. This enzyme follows instructions from a gene called the DHCR7 (7-dehydrocholesterol reductase) to function normally. However, the mutations in the DHCR7 gene cause the Smith-Lemli-Opitz syndrome. Mutation in the gene DHCR7 reduces or eliminates the activity of the enzyme 7-dehydrocholesterol reductase, thereby preventing the production of cholesterol in required quantities. Unfortunately, this also results in the build-up of toxic byproducts of cholesterol metabolism in the nervous system, blood, and other tissues. The end result of low cholesterol levels and toxic byproducts build-up disrupts normal growth and development. How exactly this process occurs is not completely understood and remains a question.
How Commonly Does Opitz Syndrome Occur?
According to research estimates, Smith-Lemli-Opitz syndrome affects one in every 20,000 to 60,000 births. It commonly occurs in white people with European ancestry. People hailing from Central European countries such as Slovakia and the Czech Republic are affected in particular. The incidence of Opitz syndrome is rarely reported in Asian and African populations.
What Are the Signs and Symptoms of Opitz Syndrome?
The signs and symptoms of Opitz syndrome can be categorized as:
1) Physical Characteristics:
- Low lying and backward rotated ears.
- Development of additional fingers and toes in hands and feet (polydactyly).
- Fused fingers and toes in hands and feet (syndactyly).
- Defects in the heart present from birth.
- Abnormal development of the kidneys, lungs, eyes, and genitalia.
- A small head (microcephaly).
- The high arched and narrow roof of the mouth (palate).
- Abnormal gums (gingiva).
- Underdevelopment of the cerebrum (the largest part of the brain).
- Short stature and restricted growth.
- Increased size of the ventricles (chambers of the heart).
2) Behavioral or Mental Characteristics:
- Low intelligence quotient.
- Hypersensitivity to different stimuli.
- Aggressiveness and self-injurious behavior.
- Autism (a neurological condition that causes challenges in communication and learning).
- Hyperactivity and sleep disturbances.
- Low-muscle tone.
- Feeding abnormalities.
- An abnormal upper body movement that lacks directional orientation.
Although several signs and symptoms are mentioned above, not all children show all the symptoms. The clinical presentation varies and usually involves a combination of the symptoms mentioned above. It also depends on the severity and extent of the disease.
How Is Opitz Syndrome Diagnosed?
The diagnosis is established after studying the signs and symptoms, biochemical testing, and genetic testing.
1. Molecular-Genetic Testing:
If the mutation in the DHCR7 gene in an affected family member, prenatal testing during pregnancy will help rule out the disease.
2. Biochemical Testing:
An abnormal concentration of the enzyme 7-dehydrocholesterol reductase in the amniotic fluid is a diagnostic feature. In addition, individuals with a family history of Opitz syndrome are known to be at a 25 % higher risk of developing the syndrome.
3. Ultrasound:
Ultrasound scanning during the prenatal period can detect fetal abnormalities. Intrauterine growth restriction (IUGR) is a common feature in affected fetuses. Facial features of Opitz syndrome can be observed around the 18th week of pregnancy. In mild cases of the syndrome, the ultrasound examination may be normal.
What Is the Treatment for Opitz Syndrome?
The treatment and management of Opitz syndrome involve a multispecialty complex approach.
1. Surgery:
Surgery can correct dysfunction in organs like the oral cavity, heart, and genitals.
2. Cholesterol Supplements:
The most common method of management includes cholesterol supplementation through diet. It is known to improve behavioral symptoms, but it does not improve developmental delay.
3. Statin Therapy:
Statins are a group of drugs that inhibit cholesterol production. Statin therapy in Opitz syndrome is known to reduce toxin build-up in the body. Simvastatin is one such drug that increases DHCR7 gene expression, leading to its increased activity.
4. In a Child - Statin therapy can be used along with surgery to repair heart defects, cleft lip, cleft palate, and other congenital disabilities is suggested. In addition, including foods rich in cholesterol in the diet may help reduce a few symptoms.
- Speech Therapies: Regular professional speech therapy improves language development, and cognitive, and learning abilities in the affected child.
- Surgeries: Multiple surgeries may be required to correct birth defects.
The following defects can be corrected surgically:
- Cleft Palate: The opening present in the roof of the mouth is corrected to improve speech and feeding in children.
- Polydactyly: Surgical removal of the extra finger or digits is done for cosmetic consideration in the early stages of life.
- Cataracts: This is a surgical procedure that corrects cloudy vision.
Orthognathic Surgeries: Surgical procedures that correct the jaw size and regular dental checkups are advised twice a year in these individuals by the age of three.
Conclusion:
Opitz syndrome is a rare autosomal recessive genetic disorder due to mutations in the gene involved in cholesterol synthesis. The cholesterol metabolism is affected in this syndrome, and as a result, there is a low cholesterol level, and toxin by-product builds up in the body. The symptoms appear as physical and behavioral abnormalities. In addition, most of the affected children show signs and symptoms of autism. After carefully studying the clinical features, biochemical tests, and genetic tests, the diagnosis is made. Treatment involves a complex multispeciality approach with surgery, cholesterol supplements, statin therapy, etc.
