PRECONCEPTION

1. Heather & Ian.

Presentation:

Malformation of the neural tube resulting in spina bifida or anencephaly

Associated Signs/Symptoms:

Talipes

Progression/Prognosis:

Variable, according to the size and level of the lesion. Hemiplegia and incontinence may be caused by the abnormality. Infants with anencephaly rarely survive more than a few hours. He or she should be given dignified care to ensure there is no discomfort suffered.

Management/Care:
All mothers who have an increased risk of having a child with a neural tube defect should be prescribed a higher dose folic acid supplement (5mg per day). This group of women includes those who:
i) have had a fetus or child with a neural tube defect
ii) had a neural tube defect themselves
iii) are at increased risk due to exposure to medications such as anti-convulsant therapy. Parents who decide to continue with the pregnancy after diagnosis of a fetal abnormality need additional support of the midwife.

Testing Screening:

Neural tube defects are usually detectable by ultrasound in the second trimester.

Common Patient/Client Issues:

All women who may become pregnant should be advised to take folic acid 0.4mg daily for at least 12 weeks before conception and for the first 12 weeks of pregnancy.

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PREGNANCY & PERINATAL PERIOD

1. Tom & Louise.

Presentation:
Chromosome structure 47,XYY

Associated Signs/Symptoms:
Tall stature, behaviour problems, slight learning delay, acne.

Progression / Prognosis:
Boys with the additional Y chromosome are usually taller than expected for their family phenotype. Behaviour problems have been reported in some children with this arrangement but many individuals with this karyotype are not diagnosed because there is no reason to suspect an abnormality.

Management / Care:
When two partners differ in their attitude to the future of a pregnancy, skilled counselling by an experienced practitioner may be helpful in enabling them to come to a resolution. Parents who have a termination of pregnancy for fetal abnormality should be offered supportive counselling before and after the termination. They may require additional support in subsequent pregnancies.

Common Patient/Client Issues:

Mothers who are offered fetal chromosome analysis should be aware that abnormalities other than Down syndrome might be detected.

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2. Emily.

Presentation:
Physical features associated with Down syndrome or trisomy 21.

Associated Signs/Symptoms:
Risk of congenital heart defect.

Progression / Prognosis:
Children with Down syndrome have hypotonia and therefore may find it difficult to feed at birth. Problems with feeding may be exacerbated if the child has a congenital heart defect. Children with trisomy 21 have delayed development and require additional educational support.

Management / Care:
The care of the child is as for any child with special learning needs. Management of a heart defect, if present is within the remit of the cardiologist and cardiac surgeon. Physiotherapy and speech therapy are helpful in supporting the child to develop physical and communication skills. The parents of a child with trisomy 21 are usually not at any significantly increased risk of having another child with the condition, the risk is up to 1% in future pregnancies unless the mother is over 40 years. The exception to this would be if the child has a translocation and then the parental chromosomes should be studied to detect a balanced translocation in the parent.

Testing/Screening:

When the child has a trisomy 21 karyotype involving a chromosome translocation, the parents should be offered chromosome analysis so that risks of trisomy 21 in another pregnancy can be assessed. If parents wish, fetal chromosome analysis on cells taken via CVS or amniocentesis can be performed. Alternatively, screening for Down syndrome using nuchal translucency measurement and biochemical testing of maternal serum does not present any risk to the fetus but does not provide a definite diagnosis.

Common Patient/Client Issues:
Parents who have had one child with a congenital abnormality are usually very anxious through subsequent pregnancies because of concern for the expected child. Anxiety can persist even after normal test results, until the baby is born.

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3. Sivia

Presentation:

Varies according to type of EDS (there are 6 types). May be hyperflexibility (unusual elasticity) of skin, hypermobile joints, excessive bruising, skin fragility.

Associated Signs/Symptoms:

Complications can include uterine or other visceral rupture, premature rupture of membranes, fragile sclera, mitral valve prolapse, scoliosis.

Progression/Prognosis:

Extremely variable due to differences in types of EDS. May be confined to relatively minor problems associated with skin and hyperflexibility and joint hypermobility but if one of the more severe types may progress to serious problems, even sudden death. Life expectancy is reduced in the Classical type due to the risk of rupture of major blood vessels.

Management/Care:

It is crucial that the condition is diagnosed correctly and therefore referral to a clinical geneticist is required if the condition is suspected. Management during pregnancy should be shared between obstetrician and a physician who is experienced in caring for patients with the condition. Close observation in an obstetric unit during labour may be appropriate if the patient is at increased risk of uterine rupture.
As healing may be adversely affected, care should be taken to avoid tissue trauma or surgery as far as possible. Sutures may need to be left in situ for longer than usual.

Testing/Screening:

A suspicion of EDS may be raised based on family history, medical history and physical examination. Diagnosis is made by examination of a skin biopsy.

Several different Ehlers-Danlos syndromes exist and the underlying genes have been identified in some. Testing for EDS Type IV, Autosomal (OMIM code: 130050) has recently been approved by the UKGTN and recommended to commissioners that they should fund testing in 2007/2008. This test is provided from Sheffield RGC. Information on the criteria that have to be fulfilled before a test is offered (the testing criteria) is provided through the web site:

http://www.ukgtn.nhs.uk/gtn/UKGTN-information/dossier/Approved-testing-criteria-forms.html

Common Patient/Client Issues: Patients are often self-conscious about the physical manifestations such as the stretchiness of the skin, bruising and unsightly scars. In a family where there have been no previous major complications experienced due to this disease, patients may underestimate the possibility of these arising.

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4. Mara

Presentation:

A person with vWD Type 1 may have such a mild presentation that they are unaware that they have the condition. The condition may present as excessive bleeding after trauma or surgery. Bleeding usually occurs after injury to the tissues rather than spontaneously.The condition may be detected in some individuals when they are tested after a diagnosis has been made in a relative.

Associated Signs/Symptoms:

Some individuals with vW Type 1 may have nosebleeds, may bruise easily and may experience bleeding from the gums.

Progression/Prognosis:

The condition is not progressive. Prognosis is good as the condition is usually mild.

Management/Care:

Those with a mild form of vWD Type 1 should notify all those involved in their healthcare.

Care during pregnancy:

Care should be managed by an obstetric specialist and haematologist who is experienced in the care of people with a clotting disorder. Delivery should be planned, taking into account the possibility of excessive blood loss. Fluid replacement may be required.

Each child of a woman with vWD Type 1 has a 50% chance of inheriting the condition and should be under the care of a paediatrician.

General Management:

Medication may be required when the individual has dental or medical treatment that may involve blood loss. Treatment may not be needed for bruising, unless severe. Bleeding in the mouth can be treated with tranexamic acid (to stabilise and slow the breakdown of the clot).

Those with vWD must be advised against taking products containing aspirin or anticoagulants such as warfarin. They should seek medical advice about taking anti-inflammatory drugs.

Testing/Screening:

Testing is undertaken where vWD is suspected because of excessive bleeding or bruising or a family history of the condition.

Tests include:

-Measurement of Factor VIII clotting activity.

- Measurement of the amount of vW factor in the blood.

-Ristocetin co-factor activity or collagen binding activity to determine how well the vW factor in the blood is working.

-vW factor multimers - to detect how the vW molecule breaks down into protein complexes.

-Platelet aggregation tests.

-Bleeding Time.

Common Patient/Client Issues:

Women who have a very mild form of the disease may be unaware of the condition.
Those who have had no problems before pregnancy may fail to understand the potential for bleeding connected with the pregnancy or delivery.
Each child of a woman with vW Type 1 has a 50% chance of inheriting the condition and she may therefore have additional concerns about the health of her baby.

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INFANCY

1. Joe.

Presentation:
Multiple or unexplained fractures and blue sclera.

Associated Signs/Symptoms:

Deafness and/or osteoporosis in adult life.

Progression / Prognosis:

There are several types of osteogenesis imperfecta. Type 1 is autosomal dominantly inherited and is usually described as a non-lethal form. There can be a great variation in the condition between members of the same family, with some having very few fractures and others being severely affected.

Management / Care:
A family history should be taken by the practitioner when a child presents with bruising or a fracture that appears unexplainable. A referral to genetic services for investigation should be made if it has not been done so already. The geneticist may be asked to see the child during the hospital admission.

Testing / Screening:
Testing for a mutation in a Type 1 collagen gene may not be possible ( because it may not be technically possible for the laboratory to test for a mutation). Testing is sometimes available in very large families through tracking of the faulty gene. However, a clinical diagnosis can often be made based on family history and physical signs such as blue sclera.

Common Patient / Client Issues:
Parents are naturally concerned that their child does not suffer additional fractures and as a result may prevent the child from being involved in physical activities. A discussion about acceptable activities that pose little additional risk to the child can be helpful. Non-accidental injury may be suspected in children who have a genetic condition that makes them susceptible to fractures or bruising.

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2. Chloe.

Presentation:
Multiple physical abnormalities and dysmorphic features at birth.

Associated Signs/Symptoms:
Learning disability.

Progression / Prognosis:
The child with an unbalanced translocation is likely to have multiple physical problems that may involve organs such as the heart or kidneys. Surgery or ongoing medical treatment may be necessary. The child will also generally have mental retardation and all milestones will be delayed. Although the child will generally continue to make progress in terms of motor skills and cognitive development throughout childhood and adolescence, he or she is unlikely to achieve full independence.

Management / Care:
When a child is born with multiple health problems, a chromosome study should be ordered. Parents of a child with an unbalanced chromosome arrangement may carry a balanced form and should be offered chromosome analysis. If they have a balanced translocation, prenatal diagnosis in future pregnancies should be offered. Biological relatives of a person with a balanced translocation may also carry the translocation. This can be determined by taking a blood sample and sending to the genetics laboratory for karyotyping. The test usually takes about 2-4 weeks. When faced with an ethical dilemma, the health practitioner needs to discuss with colleagues and consult with very experienced senior practitioners and possibly ethicists. The clinical governance team in the NHS trust may also be able to offer advice and support.

Testing / Screening:
When a chromosome anomaly is suspected, a karyotype (chromosome analysis) should be ordered. In the case of a newborn, these can be done urgently so that the results are available within several days. The karyotype information may be helpful in managing the baby's condition. When a child is found to have an unbalanced or balanced translocation, study of parental chromosomes should be offered to detect whether one parent has a balanced form of the translocation.

Common Patient / Client Issues:
It is obviously extremely distressing for parents to learn that their child has a serious genetic condition that may be life-threatening. In many cases it is difficult to give a prognosis for an individual child, often the only way of assessing how the child will develop is to wait and see. This uncertainty is also very unsettling for parents. Support from other parents whose children have a comparable condition might be helpful.

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3. Ellie.

Management / Care:
Parents of any child diagnosed with a genetic condition should be offered a referral to the genetics team. When a parent is distressed or the situation is urgent, a member of the team may be able to visit on the ward for a preliminary discussion. The physiotherapist may be able to give the mother some information but should not provide information beyond the limits of his or her expertise. It is possible that Ellie’s mother is already pregnant again. Tactfully asking whether this may be the case will provide an indication as to whether an urgent genetic appointment should be arranged.

Testing / Screening:
Cystic fibrosis is an autosomal recessive condition and each child of two carrier parents has a 1 in 4 chance of inheriting the condition. Prenatal diagnosis of the condition is possible if both the mutations in the affected child are identified. Samples from the affected child and both parents are needed for analysis to determine whether a prenatal test can be offered.

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CHILDHOOD & ADOLESCENCE

1. Jasmine.

Presentation:
At birth - hypotonia, small infant with fair skin and possibly small genitalia, hands and feet. Learning difficulties. Delayed puberty. Scoliosis.

Associated Signs/Symptoms:
Scoliosis.

Progression / Prognosis:
Feeding problems in infancy due to hypotonia. Failure to thrive. Later, obesity due to increased appetite. Delayed puberty. In childhood, perseveration and rigid thinking, with difficulty adapting to change.

Management / Care:
Involvement of a number of health professionals is needed to manage the care of a baby or child with PWS appropriately. Besides a community paediatrician, a physiotherapist is required to help the child develop muscle tone and maintained exercise to help avoid obesity. The involvement of a nutritionist or dietician is also essential. After any medical consultation, a written summary provides information for the family to use later. This is particularly vital if the family have been given unexpected news and are therefore mentally unprepared when the information is provided verbally. The local genetics service is a good source of information for the family and referral could be offered to the family. Reliable internet sources of information can also be used, such as the NIH site.

Testing / Screening:
Prader-Willi syndrome can be caused by an inherited mutation or can occur sporadically, but the person with PWS does not have a functioning copy of the gene from his or her father. It may be possible to confirm the diagnosis through DNA testing but this is not always possible. The recurrence risk for future offspring of the parents is based upon whichever genetic mechanism caused the disease in the affected child. It may be possible to offer prenatal testing in future pregnancies if the mechanism that has caused the condition in the particular family is known and recurrence risk is sufficient to warrant an invasive test in the pregnancy, with the inherent risk of miscarriage that such a test involves.

Common Patient / Client Issues:
At first, there is pressure on parents to maintain the baby's weight. Later, behaviour management is often an issue for parents, particularly related to eating.

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2. Janie.

Presentation:

Boys with Duchenne muscular dystrophy often start to walk later than usual and may appear clumsy.

Associated Signs/Symptoms:

Large calves, due to the replacement of muscle with fat.

Progression/Prognosis:

The condition progresses from birth, with affected boys finding it increasingly difficult to walk. Many affected boys start to need to use a wheelchair at around the age of 10-12 years. Death frequently occurs in the late teens or early 20s.

Management / Care:

Care for boys affected with Duchenne muscular dystrophy is often managed by a community paediatric team. Physiotherapy plays a significant role in enabling the boys to continue to be independently mobile for as long as possible and in preventing and treating chest infections. Scoliosis is a difficult problem and wheelchairs need to be fitted by trained personnel to ensure the posture in the chair is correct.

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3. James.

Presentation:

Tunnel vision (restricted field of vision), night blindness.

Associated Signs/Symptoms:

Cataracts often occur.

Progression / Prognosis:

The condition is usually progressive, although the dominant form is often less severe than either the X-linked or recessive form. In any form of Retinitis Pigmentosa (RP), total blindness may eventually occur.

Management / Care:

There is no cure for the condition. Regular ophthalmic checks are advised to screen for catraracts, which can be treated. Use of special lenses to filter light can be helpful. In a family where at least one person presents with RP, a careful history should be taken to help determine the mode of inheritance.

Testing / Screening:

Diagnosis is made by testing visual fields and examination of the eye for the pigmentary spots on the retina. Those at risk in a family may be screened regularly by these means if they wish. Genetic testing to determine if an individual has inherited the mutation may be possible if the mutation has been identified in an affected family member.

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ADULT 1

1. Bob & Carol.

Presentation:
Usually presents with mild signs and symptoms such as clumsiness, ataxia, slurred speech and memory difficulties.

Associated Signs/Symptoms:
Communication difficulties due to mechanical formation of speech and recall of words. Decreasing mobility. Dementia causes inflexibility of thought and poor executive functioning. Weight loss common due to involuntary movements and difficulties with swallowing.

Progression / Prognosis:
Huntington's disease is a neurodegenerative condition characterised by disorders of movement, depression and dementia. The natural course of the condition usually takes about 15-20 years from diagnosis to death; the primary cause of death often being pneumonia. However people who are affected have a higher risk of accidental death than members of the general population, due to the effect of the condition on their movements and judgement.

Management/Care:

Ongoing support should always be offered to those who have had a predictive test; even those who have had a 'good news' result, as they also have to adjust to their status as a person who is no longer at risk. Often offering support to the couple with encouragement to tell their children will enable them to do so eventually. For persons who are affected, a key worker should always be allocated to review the care of both the affected person and their carer(s) regularly, even in the early stages of the disease. This enables the family to become familiar with the professionals who are involved in providing care. This is important in a condition like HD, where adaptability is reduced as the disease progresses. Care is usually required by a range of professionals, including nurses, speech and language therapists, dieticians, occupational therapists, social workers, neurologists and psychiatrists. Although at present there is no cure for HD, activities of daily living can be well supported.

Testing / Screening:
There are several types of tests available. Diagnostic testing is performed if a person is showing signs or symptoms and has a family history of the disease. The test is used to confirm the diagnosis. When a person at risk wishes to know if he or she will develop the condition in the future, a predictive test is done. Several pre-test counselling sessions are mandatory during which the counsellor tries to assist the person being tested to prepare for the result. Prenatal testing of the fetus is also possible but done with caution if the parent at risk has not been tested, as the result may inadvertently inform the parent of their own status if the fetus if found to carry the mutation. In some cases, an exclusion test can be done to try to exclude the chance that the fetus has inherited the condition without doing a test for the 'at risk' parent, but samples from several family members are required to track the faulty gene from the affected grandparent through the family.

Common Patient/Client Issues:

Secrecy is a strong feature in families with a serious genetic condition such as HD.

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2. Cathy.

Presentation:

Anxiety connected with family history of breast cancer.

Associated Signs/Symptoms:

N/A

Progression / Prognosis:

Individuals who have a family history of cancer may have heightened awareness of any sign or symptom that could be indicative of cancer. In Cathy's case, she had no signs or symptoms but the diagnosis in her sister increased her cancer worry.

Managment / Care:

In Cathy's case, an explanation of the reasons for assessing her risk as low were explained to her. However, she still felt worried. Given her history, this is not surprising and acknowledgement of her fears was probably more helpful than reassurance alone. In some cases, reviewing breast awareness techniques and informing the patient that she is able to seek advice from her GP or practice nurse if she is concerned about breast changes is also helpful to the patient.

Testing / Screening:

In this case, no additional screening was indicated for Cathy, but regular mammography as part of the population screening program would be advised from the age of 50 years. When a woman is assessed as being at moderate or high risk of breast cancer, she may be offered regular breast cancer screening before the age of 50 years, but rarely at less than 40 years because the screening is not as reliable in pre-menopausal women as in those in the post-menopausal group. This is because the breast tissue is more dense in pre-menopausal women and any abnormal tissue is not seen so readily on the mammogram. For more information , the recent NICE guidelines on Familial Breast Cancer are useful.

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3. Dennis.

Presentation:

Rectal bleeding, abdominal pain, changes in bowel habit.

Associated Signs/Symptoms:

Anaemia due to blood loss, unexplained weight loss, potential bowel obstruction.

Progression / Prognosis:

Individuals with familial polyposis coli (FAP) may have polyps in the colon from adolescence or even earlier. The number of polyps increases over time. The progrssion from polyp to tumour usually occurs over the course of several years.

Management / Care:

Removal of polyps or colectomy reduces the risk of colon cancer significantly. An ileo-rectal pouch procedure can sometimes be performed to avoid the patient having a colostomy, but is not always possible due to the location of the polyps. Ongoing lifetime surveillance of any remaining colon and the upper gastro-intestinal tract for polyps is essential.

Testing / Screening:

Individuals at risk of FAP should be offered annual colonoscopy and endoscopy of the upper gastro-intestinal tract so that polyps can be identified and removed (see above). It may be possible to offer pre-symptomatic genetic testing to persons at risk if the mutation in the family has been identified. If the mutation has not been identified, linkage studies that rely on tracking the faulty gene through the family are potentially useful. Genetic testing in these families helps to identify those persons for whom colonoscopy should be offered regularly and those who do not require this type of surveillance. As colonoscopy is an invasive procedure, the ability to focus the screening program appropriately is important.

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ADULT 2

1. Gordon.

Presentation:

Memory loss,confusion, inability to problem solve, inability to perform mental tasks (such as mental arithmetic) that the individual was able to do previously, mood swings.

Associated Signs/Symptoms:

Increasing inability to care for self because of memory loss.

Progression / Prognosis:

The Alzheimer's condition progresses steadily and as yet there is no effective cure. Death ensues after a number of years.

Management / Care:

Supportive care of the affected person in a suitable environment improves quality of life and reduces the risks to the person's safety. Referral to professional centres that are able to offer specialist skills, such as memory clinics, is often helpful. Support for the carers is also essential and respite care should be offered appropriately.

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2. Eleanor.

Presentation:
Multiple cysts within the kidney, that may develop from childhood but usually appear during the teens or early adulthood.

Associated Signs/Symptoms:
Hypertension and renal failure.

Progression / Prognosis:
The majority of individuals with a mutation in one of the genes connected with adult polycystic kidney disease will have cysts by the age of 30 years. However, if a person dies at a young age, the condition may not have manifested in them by the time of their death. Their children may be at risk of the condition. In some families, Berry aneurysm is associated with polycystic kidneys.

Management / Care:
Diagnosis is usually made by ultrasound scan of the kidneys. Following diagnosis, referral to a renal physician for ongoing management is essential. Early detection and treatment of hypertension improves prognosis and eventually renal transplant may be required.

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