Genetics

Question 1

The genetic code for every feature of each human is contained where?

Answer 1

Within the nucleus of each cell of the body.

Question 2

On what molecule is the genetic code is contained within a long string of nucleotides on?

Answer 2

The genetic code is contained within a long string of nucleotides on a molecule called deoxyribonucleic acid (DNA).

Question 3

Each gene is the result of what?

Answer 3

Each gene is the result of a string of DNA that contains the instructions for how to form specific proteins. These proteins are responsible for how our body functions.

Question 4

DNA codes for hundreds to thousands of genes are bundled into individual chromosomes - what are chromosomes?

Answer 4

Chromosomes are single molecules of DNA.

Chromosomes come in pairs.

Therefore, each human has two copies of each gene, one on each chromosome in a pair. One chromosome in each pair comes from each parent.

We have 23 chromosome pairs or 46 chromosomes in total.

Question 5

Sex chromosomes vs-non sex chromosomes

Answer 5

One of the pairs of chromosomes are the sex chromosomes. The sex chromosomes are the X chromosome and the Y chromosome. Males have an X and a Y chromosome and females have two X chromosomes. The other 44 chromosomes are called autosomes. They are the non-sex chromosomes.

Question 6

What is a genotype?

Answer 6

Genotype refers to the genes that we have. For example, having the gene that codes for brown eyes.

Question 7

What is a phenotype?

Answer 7

Phenotype refers to the physical expression of the genes that we have. For example, actually having brown eyes.

Question 8

A person’s DNA is the result of half the genes from their mother combined with half the genes from their father.

A mother’s egg contains half her DNA, and a father’s sperm contains half his DNA. The DNA that makes up the egg or sperm is selected at random and is impossible to predict. The process of creating a gamete (egg or sperm) that contains half the genetic material of a normal cell is called what?

Answer 8

Meiosis

Question 9

What is the pincipal of Mendelian inheritance?

Answer 9

When there is a single gene that codes for a physical feature, the phenotype is the result of the combination of the two genes (one on each chromosome). Some genes are more dominant than others, and the phenotype will reflect the more dominant gene. This is called Mendelian inheritance.

Question 10

Dominant vs recessive genes

Answer 10

Genes that are more dominant over other genes are known as dominant, and genes that aren’t expressed when paired with more dominant genes are called recessive.

Question 11

Some genetic conditions exhibit a simple inheritance pattern called Mendelian Inheritance - what does this mean?

Answer 11

This type of inheritance only occurs where the disease is caused by a single abnormal gene on one of the non-sex chromosomes (i.e. not the X or Y chromosomes).

These chromosomes are called “autosomes”.

Question 12

Potential outcomes of inheritance of a autosomal recessive condition when two parents are carriers?

Answer 12

The children of these parents have a 1 in 4 (or 25%) chance of having the disease, and 2 in 4 (or 50%) chance of being a carrier and a 1 in 4 (or 25%) chance of having normal genes.

Question 13

When one parent has an autosomal recessive disease, and the other parent is a carrier, what are the chances of their children inheriting the condition?

Answer 13

The children of these parents have a 50% chance of having the disease and a 50% chance of being a carrier.

Question 14

Autosomal dominant condition - possible outcomes when one parent has the condition and the other parent is disease free?

Answer 14

The children of these parents have a 2 in 4 (or 50%) chance of having the disease, and 2 in 4 (or 50%) chance of having normal genes.

Question 15

What is a chromosome disorder?

Answer 15

Chromosome disorders are condition where there is either a structural abnormality, an extra abnormal portion or an abnormal number of chromosomes compared to normal.

Question 16

Deletion disorders

Answer 16

Deletion disorders occur where a portion of a chromosome is missing.

These syndromes are very rare

One example is cri du chat, which is caused by a missing portion of chromosome 5. Patients have learning, developmental and speech and language difficulties and a characteristic “cat like cry” as infants.

Question 17

Duplication disorder

Answer 17

Duplication disorders occur where a portion of a chromosome is duplicated.

The chromosome contains twice the number of copies of that gene.

One example is Charcot-Marie-Tooth, which can be caused by a duplication of the short arm of chromosome 17. Patients suffer with sensory and motor neuropathy and have characteristic pes cavus (high arching foot).

Question 18

What is a translocation disorder?

Answer 18

Translocation disorders occur where a portion of one chromosome is directly swapped with a portion of another chromosome.

The swap can be balanced (reciprocal translocations), where a portion of one chromosome is swapped with a portion of another.

Alternatively they can be unbalanced (nonreciprocal translocations), where a portion of one chromosome leaves the first chromosome and attaches to the other without any exchange taking place.

Question 19

What do translocation disorders lead to?

Answer 19

Translocation does not usually lead to a specific genetic syndrome, but often predisposes to other conditions such as cancer and infertility. One example is the “Philadelphia chromosome” translocation in acute myeloid leukaemia, which is a reciprocal translocation between chromosome 9 and chromosome 22.

Question 20

Robertsonian translocations

Answer 20

Robertsonian translocations occur in acrocentric chromosomes. These chromosomes are 13, 14, 15, 21 and 22. They have a longer long arm, which contains most of the genetic material, and a very short short arm with very little genetic information on it. When a person has a Robertsonian translocation, they loose the short arm completely, and the two long arms connect to each other at the centromere, essentially loosing a chromosome when they get rid of the two short arms. In this scenario the person is usually phenotypically normal, but has 45 chromosomes when counted and has a risk of problems in their offspring.

Question 21

What is Trisomy?

Answer 21

Trisomy is where the person has an extra chromosome.

They have a total of 47 chromosomes.

They have three copies of a particular chromosome.

Question 22

What is Patau syndrome?

Answer 22

Trisomy 13.

The syndrome varies in severity.

Patients have dysmorphic features, structural abnormalities affecting almost all areas of their body and learning disability. They have characteristic “rocker bottom feet”, where the soles of the feet are convex (rounded outwards) in shape.

Question 23

What is Edwards syndrome?

Answer 23

This is trisomy 18. The syndrome varies in severity and affects almost all areas of the body, resulting in dysmorphic features and learning disability. They also have “rocker bottom feet”.

Question 24

What is Mosaicism

Answer 24

Mosaicism is an interesting scenario where the chromosomal abnormality actually happens after conception. The abnormality occurs in a portion of cells in the body and not in others. The person therefore has different genetic material in different cells in their body. Each case is unique and the effects are unpredictable.

Question 25

“Rocker bottom feet”, where the soles of the feet are convex, is a characteristic feature of what genetic condition?

Answer 25

Patau syndrome, and also Edwards syndrome

Question 26

Trisomy 13

Answer 26

Patua syndrome

Question 27

Trisomy 18

Answer 27

Edwards syndrome

Question 28

Trisomy 21

Answer 28

Down's syndrome

Question 29

What is a mitochondrial myopathy?

Answer 29

Abnormal mitochondria lead to poor production of ATP, the molecule that provides energy in the body. Poor production of ATP leads to myopathy (abnormal muscle function). They are also responsible for rare forms of deafness, blindness, diabetes mellitus and epilepsy.

Question 30

What are mitochondria

Answer 30

Mitochondria are organelles that live inside the cell cytoplasm. The number of mitochondria in a cell varies depending on the function of that cell. Myocytes (muscle cells) have thousands of mitochondria, whereas adipocytes (fat cells) have very few. They are responsible for producing ATP for the cell. Mitochondria contain their own DNA, separate from DNA in the cell the nucleus. This DNA is arranged in a large circle, unlike the chromosomes found in the nucleus.

Question 31

Mitochondrial Inheritance

Answer 31

At the time of conception, the sperm carrying the fathers genetic material enters the egg and the DNA in the nucleus of both cells combine. The vast majority of the mitochondria in that first cell (called the zygote) come from the mother. All of the mitochondria in the sperm are in the tail, which does not enter the egg. Therefore, the father does not contribute any mitochondria to the zygote and subsequently the fetus and child. Therefore, mitochondrial DNA is primarily from the mother. This is called maternal inheritance. If we are looking at a specific disease gene in the mitochondria DNA, we need to consider that not all mitochondria within the mothers cells will be affected. The proportion of affected mitochondria that are passed to the offspring will determine whether that individual is affected.

Question 32

Diagnostic genetic testing

Answer 32

Diagnostic testing involves testing a fetus or a person for a suspected genetic condition. We can test a fetus for a genetic condition via amniocentesis. An example of this is antenatal testing for Down’s syndrome. Antenatal testing can have implications on the decision to continue the pregnancy. Where a specific condition is suspected, for example Turner syndrome, it is possible to test directly for that condition in a child or adult.

Question 33

Predictive genetic testing

Answer 33

Predictive testing involves testing a person for a specific gene mutation that has implications for them in the future. Examples are the BRCA1 breast cancer gene or the gene for Huntington’s chorea.

Question 34

Carrier genetic testing

Answer 34

Carrier testing involves testing parents or potential parents for the gene for a specific autosomal recessive condition in order to calculate the risk of passing it to their children. An example of this is testing for the cystic fibrosis gene.

Question 35

When might genetic testing be undertaken in scenarios outside of diagnostic, predictive and carrier testing?

Answer 35

Genealogical testing Forensic testing Paternity testing

Question 36

What is Karyotyping?

Answer 36

Karyotyping involves looking at the number of chromosomes, their size and basic structure.

Question 37

In what conditions might karyotyping be helpful in diagnosing?

Answer 37

Down's syndrome (trisomy 21) Turner syndrome (45 XO)

Question 38

What is microarray testing?

Answer 38

Microarray testing involves cutting up the genetic material from an individual using enzymes. Different genes will have different molecular weights. The chopped up genetic material is then applied to a plate that separates molecules of different weights into different locations. This can be used to see what genes the person expresses.

Question 39

Applications of microarray testing?

Answer 39

Screening for chromosomal abnormalities and many common genetic conditions Looking for mutations in cancer cells For research aimed at matching genes with phenotypes

Question 40

Specific gene testing

Answer 40

Specific gene testing can be done by splitting the two strands of DNA and adding a “gene probe”. The gene probe is made of single stranded DNA that contains complementary genetic code for a specific gene you want to test for. When the strands of DNA are mixed with the gene probe and the gene probe matches the genetic material on the DNA, they will stick together. This suggests the specific gene that matches the gene probe is present. This is used to confirm whether a patient has a particular gene.

Question 41

DNA sequencing

Answer 41

DNA sequencing is only used for research purposes, and has no role in routine clinical practice. This involves splitting the two strands of DNA and watching as individual nucleotides are added to a single strand of DNA, ultimately revealing the exact sequence of nucleotides in that section of DNA.

Question 42

What is Down's syndrome?

Answer 42

Down’s Syndrome is caused by three copies of chromosome 21. It is also called trisomy 21. It gives characteristic dysmorphic features and is associated with a number of associated conditions. The extent to which the person is affected and the associated conditions they have vary between individuals.

Question 43

Dysmorphic features of downs syndrome?

Answer 43

Hypotonia (reduced muscle tone) Brachycephaly (small head with a flat back) Short neck Short stature Flattened face and nose Prominent epicanthic folds (folds of skin covering the medial portion of the eye and eyelid) Upward sloping palpebral fissures (gaps between the lower and upper eyelid) Single palmar crease

Question 44

Complications of Down's syndrome?

Answer 44

Learning disability Recurrent otitis media Deafness. Eustachian tube abnormalities lead to glue ear and conductive hearing loss. Visual problems such myopia, strabismus and cataracts Hypothyroidism occurs in 10 – 20% Cardiac defects affect 1 in 3, particularly ASD, VSD, patent ductus arteriosus and tetralogy of Fallot Atlantoaxial instability Leukaemia is more common in children with Down’s Dementia is more common in adults with Down’s

Question 45

Cardiac defects which may occur alongside Downs Syndrome?

Answer 45

ASD, VSD, patent ductus arteriosus and tetralogy of Fallot

Question 46

First line antenatal Downs syndrome screening?

Answer 46

The combined test is the first line, most accurate and test of choice where possible. This test is performed between 11 and 14 weeks gestation. It involves combining results from ultrasound and maternal blood tests. Ultrasound measures nuchal translucency, which is the thickness of the back of the neck of the fetus. Down’s syndrome is one cause of a nuchal thickness over 6mm. Maternal blood tests: - Beta‑human chorionic gonadotrophin (beta-HCG). A higher result indicates a greater risk. - Pregnancy‑associated plasma protein‑A (PAPPA). A lower result indicates a greater risk.

Question 47

Antenatal testing for DS

Answer 47

The screening tests provide a risk score for the fetus having Down’s syndrome. When the risk of Down’s is greater than 1 in 150 (this result occurs in around 5% of tested women) the woman is offered amniocentesis or chorionic villus sampling. These tests involve taking a sample of the fetal cells, which then undergo karyotyping to give a definitive answer to whether the fetus is affected by Down’s or not. Chorionic villus sampling (CVS) involves an ultrasound guided biopsy of the placental tissue. This is used when testing is done earlier in pregnancy (before 15 weeks). Amniocentesis involves ultrasound guided aspiration of some amniotic fluid using a needle and syringe. This is later in pregnancy once there is enough amniotic fluid to make it safer to take a sample.

Question 48

NIPT - Downs syndrome

Answer 48

Non-invasive prenatal testing (NIPT) is a relatively new test for detecting abnormalities in the fetus during pregnancy. It involves a simple blood test from the mother. The blood will contain fragments of DNA, some of which will come from the placental tissue and represent the fetal DNA. These fragments can be analysed and detect conditions such as Down’s. NIPT is not a definitive test, but it does give a very good indication of whether the fetus is affected. This is gradually being rolled out in the NHS as an alternative to invasive testing (CVS and amniocentesis) for women that have a higher than 1 in 150 risk of Down’s syndrome.

Question 49

Management of Downs Syndrome

Answer 49

Management involves supportive care from the multidisciplinary team to help them meet their needs: Occupational therapy Speech and language therapy Physiotherapy Dietician Paediatrician GP Health visitors Cardiologist for congenital heart disease ENT specialist for ear problems Audiologist for hearing aids Optician for glasses Social services for social care and benefits Additional support with educational needs Charities such as the Down’s Syndrome Association

Question 50

Routine follow up investigations of importance for children with Down's syndrome?

Answer 50

Regular thyroid checks (2 yearly) Echocardiogram to diagnose cardiac defects Regular audiometry for hearing impairment Regular eye checks

Question 51

Prognosis of Downs Syndrome

Answer 51

Prognosis varies depending on the severity of the associate complications. The average life expectancy is 60 years.

Question 52

What is the underlying abnormality in Klinefelter syndrome?

Answer 52

Klinefelter syndrome occurs when a male has an additional X chromosome, making them 47 XXY. Rarely people with Klinefelter syndrome can have even more X chromosomes, such as 48 XXXY or 49 XXXXY. This is associated with more severe features.

Question 53

When does Klinefelter syndrome usually present?

Answer 53

When boys reach puberty

Question 54

Features of Kleinfelder syndrome?

Answer 54

Taller height Wider hips Gynaecomastia Weaker muscles Small testicles Reduced libido Shyness Infertility Subtle learning difficulties (particularly affecting speech and language)

Question 55

Klinefelter syndrome management options?

Answer 55

There is no way to treat the underlying genetic cause of Klinefelter syndrome. Treatment aims to help with the features of the condition: Testosterone injections improve many of the symptoms Advanced IVF techniques have the potential to allow fertility Breast reduction surgery for cosmetic purposes Multidisciplinary team input: Speech and language therapy to improve speech and language Occupational therapy to assist in day to day tasks Physiotherapy to strengthen muscles and joints Educational support where required for dyslexia and other learning difficulties

Question 56

Prognosis/complications of Klinefelter syndrome?

Answer 56

Life expectancy is close to normal. Infertility can occasionally be treated with advanced IVF techniques. There is a slight increased risk of: Breast cancer compared with other males (but still less than females) Osteoporosis Diabetes Anxiety and depression

Question 57

What is the underlying abnormality in Turner syndrome?

Answer 57

45 XO - female has a single z chromosome and an empty space where the second X chromosome should be

Question 58

Features of Turner syndrome

Answer 58

Short stature Webbed neck High arching palate Downward sloping eyes with ptosis Broad chest with widely spaced nipples Cubitus valgus Underdeveloped ovaries with reduced function Late or incomplete puberty Most women are infertile

Question 59

What is cubitus valgus?

Answer 59

Cubitus valgus refers to an abnormal feature of the elbow, associated with Turner syndrome When the arm is extended downwards with the palms facing forward, the angle of the forearm at the elbow is exaggerated, angled away from the body.

Question 60

Three classic features of Turner Syndrome?

Answer 60

Short stature Webbed neck Widely spaced nipples

Question 61

Turner Syndrome - associated conditions

Answer 61

Recurrent otitis media Recurrent urinary tract infections Coarctation of the aorta Hypothyroidism Hypertension Obesity Diabetes Osteoporosis Various specific learning disabilities

Question 62

Management of Turner Syndrome

Answer 62

There is no way to treat the underlying genetic cause of Turner syndrome. Treatment aims to help with the symptoms of the condition: Growth hormone therapy can be used to prevent short stature Oestrogen and progesterone replacement can help establish female secondary sex characteristics, regulate the menstrual cycle and prevent osteoporosis Fertility treatment can increase the chances of becoming pregnant Patients need monitoring for the associated conditions and complications. Treatable conditions such as hypertension and hypothyroidism should be managed appropriate.

Question 63

How is Noonan syndrome inherited?

Answer 63

Noonan syndrome is a genetic condition. There are a number of different genes that cause Noonan syndrome. The majority for cases are inherited in an autosomal dominant way.

Question 64

Features of Noonan syndrome?

Answer 64

Short stature Broad forehead Downward sloping eyes with ptosis Hypertelorism (wide space between the eyes) Prominent nasolabial folds Low set ears Webbed neck Widely spaced nipples

Question 65

Noonan syndrome: associated conditions

Answer 65

Congenital heart disease, particularly pulmonary valve stenosis, hypertrophic cardiomyopathy and ASD Cryptorchidism (undescended testes) can lead to infertility. Fertility is normal in women. Learning disability Bleeding disorders Lymphoedema Increased risk of leukaemia and neuroblastoma

Question 66

Noonan syndrome: implications on fertility

Answer 66

Men: Cryptorchidism (undescended testes) can lead to infertility. Women: Fertility is normal in women.

Question 67

What is the abnormality in Marfan Syndrome?

Answer 67

Marfan syndrome affects the gene responsible for creating fibrillin. Fibrillin is an important component of connective tissue. This means people with Marfan syndrome have features resulting from abnormal connective tissue.

Question 68

Inheritance of Marfan Syndrome

Answer 68

Autosomal dominant

Question 69

Main complication of Noonan syndrome?

Answer 69

Congenital heart disease

Question 70

Noonan syndrome management

Answer 70

There is no treatment for the underlying genetic defect. Management is supportive with involvement of the multidisciplinary team. The main complication is congenital heart disease and often patients will require corrective heart surgery.

Question 71

Features of Marfan syndrome?

Answer 71

Tall stature Long neck Long limbs Long fingers (arachnodactyly) High arch palate Hypermobility Pectus carinatum or pectus excavatum Downward sloping palpable fissures

Question 72

A patient that appears tall, has hypermobility or a murmur suggestive of mitral or aortic regurgitation, high arch palate and arm span longer than height, should be considered for what disorder?

Answer 72

Marfan syndrome

Question 73

Marfan syndrome - associated conditions?

Answer 73

Lens dislocation in the eye Joint dislocations and pain due to hypermobility Scoliosis of the spine Pneumothorax Gastro-oesophageal reflux Mitral valve prolapse (with regurgitation) Aortic valve prolapse (with regurgitation) Aortic aneurysms

Question 74

Management of Marfan Syndrome

Answer 74

The greatest risk is from the associated cardiac complications, particularly valve prolapse and aortic aneurysms. Where these complications occur they may require surgical correction. The aim of management is to minimise the blood pressure and heart rate to minimise the stress on the heart and the risk of complications developing. This is achieved by lifestyle changes, such as avoiding intense exercise and avoiding caffeine and other stimulants. ****Preventative medications such as beta blockers and angiotensin II receptor antagonists can also help reduce the risk of complications.**** Pregnancy has to be carefully considered, as it carries a significant risk of developing aortic aneurysms and associated complications. Physiotherapy can be helpful in strengthening joints and reducing symptoms arising from hypermobility. Genetic counselling is important in considering the implications of having children that may be affected by the condition. Patients are also regularly followed up and monitored for complications. This often involves yearly echocardiograms and review by an ophthalmologist.

Question 75

What is the genetic abnormality in Fragile X syndrome?

Answer 75

Fragile X syndrome is caused by a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome.

Question 76

What is the role of the abnormal gene in Fragile X syndrome?

Answer 76

The FMR1 gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain.

Question 77

Inheritance pattern of fragile X syndrome

Answer 77

It is X-linked, but it is unclear whether it is dominant or recessive. Males are always affected, but females can vary in how much they are affected. This is because females have a spare normal copy of the FMR1 gene on their other X chromosome. When the mother is phenotypically normal, the affected child may have inherited the X chromosome from their mother, or it may result from a de novo (random) mutation.

Question 78

Features of Fragile X syndrome?

Answer 78

Fragile X syndrome usually presents with a delay in speech and language development. Other features are: Intellectual disability Long, narrow face Large ears Large testicles after puberty Hypermobile joints (particularly in the hands) Attention deficit hyperactivity disorder (ADHD) Autism Seizures

Question 79

Management of Fragile X syndrome?

Answer 79

There is no cure for the condition. Management is supportive and involves treating the symptoms. This involves the multidisciplinary team to support the learning disability, manage autism and ADHD and treat seizures if they occur. Life expectancy is similar to the general population depending on associated disabilities and complications.

Question 80

What is the underlying abnormality in Prader-Willi Syndrome?

Answer 80

Prader-Willi Syndrome is a genetic condition caused by the loss of functional genes on the proximal arm of the chromosome 15 inherited from the father. This can be due to a deletion of this portion of the chromosome, or when both copies of chromosome 15 are inherited from the mother.

Question 81

Features of Prader Willi syndrome?

Answer 81

Constant insatiable hunger that leads to obesity Poor muscle tone as an infant (hypotonia) Mild-moderate learning disability Hypogonadism Fairer, soft skin that is prone to bruising Mental health problems, particularly anxiety Dysmorphic features Narrow forehead Almond shaped eyes Strabismus Thin upper lip Downturned mouth

Question 82

Feeding in Prader-Willi syndrome

Answer 82

A key feature everyone remembers for Prader-Willi syndrome is the the insatiable hunger. Feeding can often be a challenge initially due to hypotonia and it is only later that the food seeking and excessive eating occur.

Question 83

Management of Prader-Willi Syndrome

Answer 83

There is no cure. Carefully limiting access to food under guidance of a dietician is required to control weight. This usually requires locking food in cupboards, putting a lock on the fridge and even controlling access to rubbish bins. Under dietician guidance they usually require a lower than normal calorie intake, particularly as they tend to have lower activity levels due to poor muscle strength and tone. Everyone that is in contact with the child will need to be educated about limiting access to food, including teachers, carers and relatives. Growth hormone is indicated by NICE as a treatment for Prader-Willi Syndrome, aimed at improving muscle development and body composition. Supportive care from the multidisciplinary team to manage features: Dieticians play a very important role Education support Social workers Psychologists or psychiatrists Physiotherapists Occupational therapists

Question 84

Nice recommended medical treatment of Prader Willi syndrome?

Answer 84

Growth hormone is indicated by NICE as a treatment for Prader-Willi Syndrome, aimed at improving muscle development and body composition.

Question 85

Angelman syndrome: features

Answer 85

Delayed development and learning disability Severe delay or absence of speech development Coordination and balance problems (ataxia) Fascination with water Happy demeanour Inappropriate laughter Hand flapping Abnormal sleep patterns Epilepsy Attention-deficit hyperactivity disorder Dysmorphic features Microcephaly Fair skin, light hair and blue eyes Wide mouth with widely spaced teeth

Question 86

Management of angleman syndrome

Answer 86

Like many other genetic syndromes, there is no cure and management focuses on a multi-disciplinary team approach to managing individual problems and supporting the patient and carers holistically. Parental education Social services and support Educational support Physiotherapy Occupational therapy Psychology CAMHS Anti-epileptic medication where required

Question 87

What is the abnormality behind Angelman syndrome?

Answer 87

Angelman syndrome is a genetic condition caused by loss of function of the UBE3A gene, specifically the copy of the gene that is inherited from the mother. This can be caused by a deletion on chromosome 15, a specific mutation in this gene or where two copies of chromosome 15 are contributed by the father, with no copy from the mother.

Question 88

What is the underlying abnormality of William syndrome?

Answer 88

William syndrome is caused by a deletion of genetic material on one copy of chromosome 7, resulting in the person only having a single copy of the genes on this deleted region (on the other chromosome 7). It usually the result of a random deletion around conception, rather than being inherited from an affected parent.

Question 89

Features of William Syndrome?

Answer 89

Broad forehead Starburst eyes (a star-like pattern on the iris) Flattened nasal bridge Long philtrum Wide mouth with widely spaced teeth Small chin Very sociable trusting personality Mild learning disability

Question 90

Distinctive features to remember with William Syndrome

Answer 90

The distinctive features to remember with William syndrome are the very sociable personality, the starburst eyes and the wide mouth with a big smile. It is worth remembering the association with supravalvular aortic stenosis and hypercalcaemia, as these are unique features

Question 91

William Syndrome - aortic stenosis

Answer 91

Supravalvular aortic stenosis (narrowing just above the aortic valve) Attention-deficit hyperactivity disorder Hypertension Hypercalcaemia

Question 92

Management of William syndrome

Answer 92

Like many other genetic syndromes, there is no cure and management focuses on a multi-disciplinary team approach to managing individual problems and supporting the patient and family. Echocardiograms and blood pressure monitoring are important to assess for aortic stenosis and hypertension. A low calcium diet may be required to control hypercalcaemia, and they should avoid calcium and vitamin D supplements.

Question 93

Achondroplasia

Answer 93

Achondroplasia is an autosomal dominant disorder associated with short stature. It is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene. This results in abnormal cartilage giving rise to: short limbs (rhizomelia) with shortened fingers (brachydactyly) large head with frontal bossing and narrow foramen magnum midface hypoplasia with a flattened nasal bridge 'trident' hands lumbar lordosis In most cases (approximately 70%) it occurs as a sporadic mutation. The main risk factor is advancing parental age at the time of conception. Once present it is typically inherited in an autosomal dominant fashion.

Question 94

What might trisomy 21 result from?

Answer 94

In DS the individual has an extra chromosome 21. This is the most common autosomal trisomy. Trisomy 21 may result from: * Meiotic non-disjunction (95%). * Robertsonian translocation (5%). * Mosaicism (1%).

Question 95

What is Patau syndrome?

Answer 95

Trisomy 13 is also called Patau syndrome. Clinical features are structural defects of the brain, small eyes and other eye defects, cleft lip and palate, polydactyly and cardiac and renal abnormalities.

Question 96

What is Edwards' syndrome?

Answer 96

Trisomy 18 is also called Edward’s syndrome. Clinical features are low birth weight, prominent occiput, small mouth and chin, flexed overlapping fingers, ‘rocker-bottom’ feet and cardiac and renal abnormalities.

Question 97

What translocation mutation in a parent increases a childs risk of down syndrome?

Answer 97

A parent with a translocation mutation of chromosome 14 and 21 When an extra chromosome 21 is joined onto another chromosome – usually 14 but occasionally 13, 15, 21, 22 and Y – it is known as a Robertsonian translocation. A chromosomal translocation can give rise to three copies of chromosome 21. Known as an unbalanced translocation. It often arises from a parent who has a balanced Robertsonian translocation. Translocation DS has a 3% change of recurring again if the father carries the translocated chromosome and 10-15% if the mother does