On this Learning Station, you can read and test your knowledge. Tap on a book to open its chapter list. In each chapter, you can take a quiz to test your knowledge.
To take tests, you must register with your email address or cell number. It is free to register and to take tests.
For help email email@example.com or call +27 76 657 0353.
Learning is easiest with printed books. To order printed books, email firstname.lastname@example.org or call +27 76 657 0353.
Visit bettercare.co.za for information.
Take the chapter test before and after you read this chapter.
First time? Register for free. Just enter your email or cell number and create a password.
When you have completed this unit you should be able to:
This is an abnormality (mutation) in a single gene which results in a genetic disorder (birth defect). Single gene defects cause many structural and functional (biochemical or metabolic) birth defects. The number of chromosomes is normal with a single gene defect.
A single gene defect may be inherited in a number of different patterns:
In addition, a single gene defect may be due to a new mutation (autosomal dominant or X-linked recessive). With a new mutation affected individuals will not have a family history of that condition.
Single gene defects cause clinical conditions resulting from mutations in a single gene.
Waardenburg syndrome, oculocutaneous albinism and haemophilia are typical examples of disorders due to single gene defects with different patterns of inheritance. They illustrate many of the problems and principles of care and management for people with single gene defects, and their families.
Waardenburg syndrome is an inherited disorder that is made up of a recognisable collection of clinical features including deafness. It is the commonest cause of inherited deafness associated with a known syndrome in southern Africa.
Waardenburg syndrome is an autosomal dominant disorder:
Waardenburg syndrome is inherited as an autosomal dominant disorder.
Waardenburg syndrome is rare. It occurs in about 1 in 30 000 people in all populations.
In southern Africa approximately 4% of people with profound deafness have Waardenburg syndrome. This is similar to studies from other parts of the world where the prevalence of Waardenburg syndrome amongst deaf people varies from 2 to 5%.
The main clinical features of Waardenburg syndrome are:
Individuals with Waardenburg syndrome can be deaf and have a characteristic white forelock.
No. Three or more of the main features must be present to consider the clinical diagnosis. In Waardenburg syndrome, as is found in many other syndromes, the number and severity of the clinical features present can vary greatly. This is called variation in expression of the syndrome (i.e. not all the features are expressed).
Yes. The gene for Waardenburg syndrome can be identified to confirm the diagnosis. However, the test is expensive and currently not undertaken in South Africa.
No. However, infants and children with deafness from any cause, including Waardenburg syndrome, are often considered to be developmentally delayed. This is because of the lack of speech and inability to communicate. If the problem is discovered early and appropriate speech therapy started, many of the developmental problems may be overcome and the person is shown to have normal intelligence.
In people with Waardenburg syndrome, as with all cases of infant and childhood deafness, it is very important to diagnose their deafness as early as possible to ensure they can start early with intervention programmes. This will ensure the best long-term outcome for the person’s communication ability. The early clinical confirmation of the diagnosis of Waardenburg syndrome is also important so that genetic counselling can be offered to the family.
Managing the deafness:
The early diagnosis of deafness, in infancy if possible, is important so speech and communication therapy can be started early ensuring the best long-term results. Assessment to decide if hearing aids may benefit the infant or child should also be done as early as possible. Assessment and initial speech therapy need to be done at a specialised centre. Ongoing day-to-day speech therapy in areas far from such centres may be made possible for infants and young children with the help of community-based rehabilitation workers. However, to achieve the best results, these children will need to regularly attend centres for specialised ongoing assessment and therapy and eventually need to go to schools for the auditory disabled (deaf).
Manage repeated eye infections:
Conjunctivitis needs to be treated with repeated swabbing of the eye with clean water (boiled and then cooled), massaging the tear duct, and antibiotic drops or ointment if indicated. If the problem recurs often then surgical probing of the tear duct can be performed.
Genetic counselling and psychosocial support.
Genetic counselling is a major part of the care of people with Waardenburg syndrome and their family, especially the parents. The parents need to be educated and informed about:
The parents, family and child with Waardenburg syndrome need to be offered ongoing psychosocial support as with all individuals who have a congenital disability. There is currently no support group for Waardenburg syndrome in South Africa.
To assess this risk, the parents have to be examined to see if one of them has signs of Waardenburg syndrome. Because of variation of expression of the syndrome it may not have been diagnosed in one of them, as their symptoms and signs may not be as severe or numerous as in their child. For example, an affected parent may not necessarily be deaf.
If a parent is diagnosed with Waardenburg syndrome, then all future children of that parent have a 1 in 2 (50%) risk of having Waardenburg syndrome. These children with Waardenburg syndrome, when they have grown up and have their own children, will also have a 1 in 2 (50%) risk of passing the syndrome to each of their offspring. This is typical of an autosomal recessive disorder.
If both parents of a child with Waardenburg syndrome are normal, then the cause of Waardenburg syndrome in the child is due to a new mutation. Future children of that couple will have only a very small risk of being affected with Waardenburg syndrome. But the affected child will have a 1 in 2 (50%) risk of having an affected child when he or she becomes a parent.
Yes. Because the genes for Waardenburg syndrome are known, it is possible to do prenatal diagnosis. However, as the test is not currently offered in South Africa, prenatal diagnosis of Waardenburg syndrome is not practical.
Albinism is an inherited condition. The clinical signs and symptoms of albinism are caused by a lack of melanin in the cells of the body. Melanin is the pigment that gives colour to the skin, hair and eyes.
Yes, there are different forms of albinism:
Oculocutaneous albinism is the result of a lack of pigment in the eyes, skin and hair.
OCA is inherited as an autosomal recessive condition. Therefore, a person affected with OCA has received two copies of the abnormal gene (homozygous) that is responsible for melanin production (i.e. one abnormal gene from each parent). As a result, the cells of an affected individual are unable to produce normal amounts of pigment and, therefore, they are very pale.
Each parent of an affected individual has one normal and one abnormal copy of the pigment gene (i.e. is heterozygous). Because they have one normal gene that can produce melanin, they have normal pigmentation and do not show signs of OCA.
Oculocutaneous albinism is inherited as an autosomal recessive disorder.
Oculocutaneous albinism is the commonest single gene disorder in South Africa. The population prevalence of OCA in the Black population is 1 in 4000. However, it is even higher in those communities that accept intermarriage (consanguinity) as part of their culture (e.g. the Venda, Tswana, Pedi and Southern Sotho peoples). The population prevalence of OCA in other ethnic groups in South Africa is not known.
Oculocutaneous albinism is the commonest single gene disorder in South Africa.
People affected with OCA have normal physical and facial features, but have markedly decreased pigmentation of their skin, hair and eyes resulting in all these features being pale. Black people with OCA are, therefore, easily recognised. In White people, OCA is less obvious. The features of OCA are:
They have pale skin which is very sensitive to sunlight.
A black African with OCA usually has pale or corn-coloured hair. The hair colour in a few individuals may be brown or reddish (rufous).
Black African people with OCA have brown eyes, but their eyes may be lighter brown than normal. They have numerous eye problems.
All people with oculocutaneous albinism have problems with their eyesight.
Normally, melanin prevents the sun’s ultraviolet rays being absorbed by the skin. If melanin is not present in adequate amounts, the ultraviolet rays in sunlight penetrate and damage the skin. Problems resulting from a lack of pigmentation in the skin include:
Research from South Africa indicates that people with OCA are now generally well accepted in the community, and they in turn appear to be reasonably well adjusted. Myths regarding people with OCA are, however, plentiful, and it has been reported that mothers of newborns with OCA experience problems bonding with their infants and may suffer from depression, similar to that described by mothers with other birth defects.
Skin cancer is a common complication of oculocutaneous albinism.
These are used to try and explain the unexpected birth of an infant with OCA. They include that the birth is a punishment for some supposed bad deed committed by the parent(s); that the mother conceived during menstruation; that the mother must have come into contact with a person with albinism during pregnancy; that the mother ate an excess of certain foods or had an infection during pregnancy.
These are about special qualities that people with OCA supposedly have. One of the common beliefs is that people with OCA may have special religious, spiritual or supernatural power. People with OCA are often considered either very intelligent or intellectually disabled.
The death of people with OCA is surrounded with superstition. It is widely believed that they do not die, but rather disappear or vanish.
No. Children with OCA generally have a normal intelligence and are not intellectually disabled. Due to their visual disability, infants and young children may present with evidence of developmental delay. Older children may have schooling problems due to their poor vision or psychosocial problems. However, if these problems are recognised early and correctly treated with eye and visual care, early intervention programmes and counselling, they can be overcome.
The life expectancy of people with OCA should be similar to that of normal people. However, due to the high risk of developing skin cancer, many unfortunately die in early adult life if not correctly treated and counselled. In Tanzania and Nigeria, countries in the tropics and close to the equator, only 10% of people with OCA live longer than 30 years. No figures on life expectancy are currently available for South Africa. However, it is considered to be better than the figure for Tanzania and Nigeria as South Africa is mostly outside of the tropics.
Many people with oculocutaneous albinism die of skin cancer.
Early clinical diagnosis:
The first step in caring for people with OCA is to make an early, correct diagnosis. OCA is a clinical diagnosis and is usually made at the birth of the infant, especially in the black African infants in whom the diagnosis is very obvious. However, the clinical signs can be more difficult to recognise in White or Asian infants.
Good skin and eye care:
Good skin and eye care is essential to prevent skin cancer and progressive loss of eyesight.
Neurodevelopmental therapy, special education and rehabilitation:
This should be provided in the community, if possible, to enable these children to learn and develop normally.
Genetic counselling and psychosocial support.
It is essential for people with OCA to reduce their exposure to sunlight to the greatest extent possible. As it is not possible for a person with OCA to remain out of the sun continually, when they do go outdoors they should wear clothes to cover as much skin as possible, i.e. long trousers or skirts, long-sleeved tops or shirts, and hats with wide brims.
Sun-exposed skin, especially hands, arms and face, should be covered with cream containing sunscreen (sun barrier creams). Cream with sun protection factor (SPF) of 30 or greater must be used. Moisturising cream should be used on dry, cracking or chaffed skin, and skin infection should be treated vigorously with antiseptics and antibiotics if clinically indicated. Unfortunately many clinics do not have sun barrier creams. They are expensive to buy.
Adolescents and adults with OCA should be aware of the dangers of skin cancer. They should be taught how to recognise areas of skin cancer so that they know what to look for to be able to suspect and possibly diagnose cancer as early as possible (e.g. sores that do not heal). In addition they should have yearly examinations to exclude the development of skin cancer.
Good skin protection against sunlight is essential to prevent skin cancer.
People with OCA need to protect their eyes from the harmful effects of sun and bright light by avoiding it where possible and wearing protective eyewear (appropriate dark glasses with an ultraviolet screen) and broad-brimmed hats. In this way, further damage to their visual disability can be minimised.
All people with OCA should have regular ophthalmic or optometric assessments from infancy. This is necessary to ensure they obtain the correct glasses and treatment for their individual problems. This gives them the best chance of reasonable vision and ensures that their sight is not damaged by the lack of eye care.
Good eye care, protection from the sun, and the correct glasses are essential to protect eye sight.
Genetic counselling is a major part of the care of people with OCA and their family, especially their parents. The parents need to be educated and informed about:
The parents, family and person with OCA need to be offered ongoing psychosocial support.
OCA is an autosomal recessive condition. As carriers of a single abnormal OCA gene, parents of a child with OCA have a 1 in 4 risk (25%) of having a further affected child in every future pregnancy. With another partner, the chance of either parent having an affected child is very small.
The gene for OCA has been identified and, therefore, it is possible to offer prenatal diagnosis for OCA to parents who both carry the abnormal gene. This can only be done after the parents receive genetic counselling. Genetic counselling is ideally undertaken before conception, or in the first 10 weeks of the pregnancy. The prenatal gene test is done on fetal cells obtained by amniocentesis at 16 weeks. Once the result of the prenatal test is available, further genetic counselling will be necessary to discuss these results.
People with OCA, as with all individuals who have a congenital disability, suffer lifelong problems which require lifelong care. The burden of the disorder is experienced not only by the affected person, but also the family, especially parents, brothers and sisters. Mothers of newborns with OCA need psychosocial support to help them accept and bond with their infant, and overcome possible depression. In addition, the problem is genetic and thus there is the possibility for the parents, the affected person and other family members to also have children affected with OCA. Support, help and reassurance in these circumstances may be a lifelong need.
Professional psychosocial support can be obtained from:
Haemophilia is an inherited, lifelong bleeding disorder which affects mainly males.
There are two types of haemophilia, haemophilia A and haemophilia B. Haemophilia A (classical haemophilia) is the common form of haemophilia. Both types present clinically as a bleeding problem.
Haemophilia A is caused by a lack of normal functioning clotting factor VIII (eight) while haemophilia B is caused by a lack of normally functioning clotting factor IX (nine).
Haemophilia is a bleeding disorder due to the lack of a normal clotting factor.
Both types of haemophilia are inherited as X-linked recessive disorders. There are different single gene defects on the X chromosome for haemophilia A and haemophilia B on the X chromosome.
A woman with a haemophilia gene (i.e. an abnormal gene) on only one X chromosome is a carrier (i.e. she is a heterozygote). Because she has a normal gene on her other X chromosome, she will still be able to produce enough clotting factor. If she passes the X chromosome containing the abnormal gene on to her daughter, then her daughter will also be a carrier.
If a son inherits the X chromosome with the haemophilia gene from his mother, he will have haemophilia as his short Y chromosome does not have the gene to produce the clotting factor.
Haemophilia is inherited as an X-linked recessive condition. Women carry the abnormal gene and their sons are at 50% risk of inheriting haemophilia.
Yes. About 10% of female carriers have signs of mild haemophilia. All patients with moderate or severe haemophilia are males.
In South Africa, haemophilia A has been found in 1 in 5000 white males but only 1 in 20 000 black males. Due to poor socioeconomic conditions and inadequate access to health care in many black communities, some black people with haemophilia A may not be diagnosed and registered. Others may die very young with severe bleeding without the diagnosis being made. Therefore the population prevalence is less than expected.
People with haemophilia present with excessive bleeding. The bleeding may be in the skin and mucous membranes (bruising), muscle, joints, internal organs or brain. Infants usually bleed into soft tissues while older boys usually bleed into joints.
The severity and frequency of bleeds depends on the concentration of clotting factors VIII and IX in the patient’s blood:
Bleeding is unusual in newborns but infants with haemophilia can bleed from circumcision sites. Infants with severe haemophilia will bleed into muscles from injection or needle-stick sites or spontaneously into cephalhaematomas or within the skull (intracranial bleed).
Yes. If haemophilia is suspected, the following tests can be done to confirm the diagnosis:
These relate to the severity and site of bleeding. A person with haemophilia may have bleeding problems in any part of the body. Major bleeds can cause death or disability and they require immediate treatment with the correct clotting factor. Minor bleeds also require treatment and, depending on their position, may cause complications.
Sites into which bleeding occurs include:
Joint bleeds (haemarthrosis) into the knees, elbows and ankles are common and are the most disabling complication of severe haemophilia. Joint bleeds present with pain, swelling, stiffness and refusal to move that limb. Treatment must be started with the correct clotting factor every 12 to 24 hours, and the joint must be splinted. Ice packs can be used to lessen the swelling. Failure to effectively treat these bleeds will eventually result in affected joints becoming fixed and not able to move due to the damage that the blood causes in the joint. Arthritis can develop. Physical disability resulting from joint damage is a major problem for people with haemophilia in developing countries.
Bleeding into the organs of the abdomen and chest is less common but may be spontaneous and serious. Abdominal pain in a boy with haemophilia always suggests a bleed.
Intracranial bleeding (within the skull) can be spontaneous or result from minor trauma, often not recognised in a child. Intracranial bleeding presents as headache, vomiting, and lethargy or irritability. Urgent clotting factor replacement is needed with internal bleeding.
The diagnosis of haemophilia should be suspected if a male presents with:
A female carrier with mild haemophilia may be suspected if she has a close male relative (brother, son or maternal uncle) with haemophilia and presents with heavy periods (menorrhagia), easy bruising or bleeding after trauma, surgery or childbirth.
It is suspected that the diagnosis of haemophilia is being missed in many cases in South Africa. Correct diagnosis of haemophilia is needed to be able to give the correct treatment and genetic counselling. A PTT test can be used to confirm that the bleeding is due to a lack of one of the clotting factors.
Bleeding is rapidly controlled by giving intravenous factor VIII concentrate in haemophilia A and factor IX concentrate in haemophilia B. This is to stop further bleeding and will assist in reducing pain and lowers the risk of developing serious complications, especially chronic joint disease. For major bleeds, clotting factors should be given in hospital. However, patients over two years of age can often be treated at home.
Where possible, children with severe haemophilia are now being given prophylactic home therapy with clotting factor three times a week to prevent bleeding episodes from occurring.
Once factor VIII or IX concentrate has been given, further treatment of the problems may be needed, such as splinting during recovery, and physiotherapy to help preserve movement in the recovery phase. All operations need to take place under the cover of clotting factor replacement to ensure that there will be no excessive bleeding.
Never give aspirin or non-steroidal anti-inflammatory drugs (e.g. Voltaren and Indocid) to someone with haemophilia as these drugs increase the risk of bleeding. Haemophilia is a serious condition and must be managed in partnership with a provincial haemophilia treatment centre. Paracetamol (Panado) can safely be used for pain relief.
As soon as bleeding is suspected in someone with haemophilia, immediate treatment with the correct clotting factor concentrate must be started.
01 405 2136
Red Cross Children Hospitals
021 658 185
021 938 464
Haemophilia treatment centre
031 360 3680
083 265 248
East London Health Complex
043 709 2370
011 488 3294/86
Dr C Sutton
082 800 6778
041 405 9111
Prof B Ogunsanwo
084 321 2482
Genetic counselling is an important part of the care of people with haemophilia, and their families. All need to be educated and informed on:
The parents, family and child with haemophilia need to be offered ongoing psychosocial support as they have problems which require lifelong care. The burden of the disorder and the care is experienced not only by the affected person, but also the family, especially parents, brothers and sisters. Support, help and reassurance in these circumstances may be obtained from:
If the mother is a carrier of the abnormal gene then in each of her future male pregnancies she will have a 1 in 2 (50%) chance of having a son affected with haemophilia.
If the mother is NOT a carrier of an abnormal haemophilia gene then her risk for having another son with haemophilia is very small.
The risk is 1 in 2 (50%). This is the same as the risk of having an affected son. The carrier mother has a 50/50 chance of giving her X chromosome with the abnormal gene to each of her children. This doesn’t mean that half her children will get it – they may all or none end up with it. The carrier daughters, like their mothers, have the same risks (50%) of passing the abnormal haemophilia gene on to their children.
If a couple has a son with haemophilia, then it is important to find out if his mother is a carrier of an abnormal haemophilia gene. There are two ways of finding this out:
Men have one X and one Y chromosome. If a man has haemophilia he will have an abnormal haemophilia gene on his X chromosome but not on his Y chromosome (i.e. an X-linked recessive disorder). When he has children he gives his Y chromosome, with the no haemophilia gene, to his sons who will get their X chromosome from their mother. Therefore, if the mother is not a carrier of an abnormal haemophilia gene, their sons will not have haemophilia.
He will give his X chromosome, with the abnormal haemophilia gene, to his daughters who will all, therefore, be carriers of the abnormal haemophilia gene.
Yes. Because the abnormal gene for haemophilia can be tested for, a woman who is a carrier of this abnormal gene can be offered prenatal diagnosis. This is done after she and her partner have had genetic counselling.
It is best to provide genetic counselling and to determine whether the woman is a carrier before she falls pregnant. Prenatal diagnosis is then done early in pregnancy. This is carried out by obtaining fetal cells by amniocentesis, and testing these cells to see if they have an abnormal haemophilia gene (A or B).
A woman with Waardenburg syndrome delivers her first-born infant who also has a white forelock. She asks whether all her infants will have the same problem.
Very blue eyes, bushy eyebrows, deafness (25 to 50%) and a white forelock (30 to 40%). Premature greying of the hair and partial albinism is common.
It is usually inherited as an autosomal dominant disorder. This woman’s child has inherited her dominant gene for Waardenburg syndrome. Each of her future children will have a 50% chance of inheriting the condition.
No. As with many autosomal dominant disorders, the condition may appear as a new mutation and will not be inherited from a parent. About a third of patients with Waardenburg syndrome do not have a family history of the condition.
Severe sensory deafness affecting both ears. As a result they often have speech difficulties which affect their schooling and socialisation. They are not intellectually disabled.
It is not common (about one in 30 000 people). However, about 4% of people with severe deafness have the condition.
The first-born infant of black parents has very pale skin and hair with light-brown eyes. They notice that the child has abnormal eye movements and appears to have poor vision. The nurse at the local clinic tells them that they should use skin cream on the infant to prevent sunburn. The clinic does not have sun protection cream and the parents cannot afford to buy the cream.
The infant probably has oculocutaneous albinism (OCA) as there is lack of pigment in the skin, hair and eyes. This is the common form of albinism in southern Africa.
Yes. All people with OCA have eye problems and most have poor vision. This infant has the typical jerky eye movements known as nystagmus.
Because they lack adequate pigment (melanin) to protect the skin from the ultraviolet rays of the sun, they suffer severe skin damage. Sunburn and blistering are common, resulting in rapid aging of the skin.
Infections and cancer.
Many die young as a result of skin cancer. This emphasises the importance of sun protection. The life expectancy of people with OCA in South Africa is not known.
A woman, whose husband has oculocutaneous albinism, visits her general practitioner as they plan to start their family. She wants to know the risk of their children also being affected. She mentions that he gets upset as many people think he is intellectually disabled and some children are afraid of him
It is inherited as an autosomal recessive disorder. Therefore, the father must have two abnormal genes for melanin production (homozygous). Each of his children will have a 50% chance of inheriting one of his genes containing the single gene defect for OCA. If the mother does not have this gene, then these children will appear normal but will be carriers (heteroygotes). It is possible to test the mother to see whether she is a carrier. If she is, then the couple should be sent for genetic counselling.
The prevalence in the black population is 1 in 3900, making it the commonest single gene disorder in the country. The prevalence in other ethnic groups is unknown.
No. They have normal intelligence. However, their many eye problems results in poor vision and this may interfere with their schooling.
Because people with oculocutaneous albinism look different. Children should not be afraid of people with oculocutaneous albinism as they are normal people except for their colouring. There are also many myths about people with oculocutaneous albinism. In some communities these people are believed to have special powers.
The gene for OCA is known and, therefore, prenatal diagnosis is possible. Couples at risk of having a child with OCA should receive genetic counselling, preferably before they start a family.
A newborn infant bleeds very heavily after circumcision. The mother reports that her uncle died of haemorrhage as a teenager after an operation, and that her brother is severely disabled due to repeated bleeds into his joints. She and her husband are well and have never had a bleeding problem.
With excessive bleeding. Heavy bleeding after a circumcision is a typical way that haemophilia may present. Patients may bleed spontaneously or after trauma or surgery.
Yes. Patients with severe haemophilia, who have less than 1% of the normal clotting factor activity, often bleed into big joints such as the knee, elbow or ankle. Repeated bleeds damage the joint resulting in pain and stiffness.
An inadequate amount of clotting factor VIII (in haemophilia A) or factor IX (in haemophilia B).
Both haemophilia A and B are inherited as X-linked recessive disorders. The females in the family carry the recessive gene on one of their X chromosome. Fifty percent of their male children will inherited the X chromosome with the abnormal gene, and as a result will have haemophilia. Both parents are usually clinically well without a bleeding problem although 10% of carrier mothers may have a mild problem.
The PTT (partial thromboplastin test) is abnormal and the concentration of either factor VIII (haemophilia A) or factor IX (haemophilia B) is low. The lower the concentration the more severe is the haemophilia. Haemophilia A is more common than haemophilia B.
The missing clotting factor should urgently be replaced by intravenous transfusion of factor VIII for haemophilia A or factor IX for haemophilia B. This is best done by immediate consultation with a haemophilia treatment centre.