EM genetics

Question 1

In muscular dystrophy, several muscle enzymes are released from the sarcoplasm when damaged; the most common enzyme measured is

Answer 1

creatine kinase (CK).

Question 2

___ is the most common skeletal dysplasia, is transmitted as an autosomal dominant trait; although, 75% of affected infants result from a new mutation. Fetal diagnosis can be suspected with long-bone foreshortening on third trimester ultrasounds.

Answer 2

Achondroplasia. At birth the diagnosis can be confirmed by a skeletal survey showing a contracted skull base, square-shaped long bones, trident hands, proximal femur radiolucency, and proximal segment long-bone shortening. Macrocephaly and frontal bossing may also be evident.

Question 3

signs in the first year with achondroplasia ,

Answer 3

hypotonia and delayed motor development are also noted; although, normal development is usually eventually achieved.

Question 4

Normally only a small amount of AFP gains access into the amniotic fluid. However, when there is an _______ more AFP escapes into the amniotic fluid.

Answer 4

open neural tube defect (anencephaly or spina bifida) or there is an abdominal wall defect (omphalocele or gastroschisis)

Question 5

Mutations in the PTEN gene can cause a number of conditions as part of the PTEN hamartoma tumor syndrome umbrella, which includes:

Answer 5

Cowden syndrome (an adult-onset syndrome characterized by macrocephaly, increased risk of thyroid, endometrial and breast cancer, intestinal polyps, fibrocystic breasts, lipomas, fibromas, genitourinary tumors, uterine fibroids, and facial papules)
Bannayan Riley Ruvalcaba (with features including macrocephaly, intellectual disability, hamartomatous intestinal polyps, lipomas and pigmented macules of the glans penis among others)

Question 6

Given the presence of macrocephaly, learning disabilities, and abnormal pigmentation on the glans penis of this patient, PTEN gene analysis to rule out _______

Answer 6

Bannayan-Riley- Ruvalcaba syndrome

Question 7

________ is a condition that causes facial clefting and lower lip pits or mounds. Affected individuals are typically cognitively normal. Individuals with VWS can show congenital lower-lip pits or fistulas or small mounds with a sinus tract leading from a mucous gland of the lip. This condition is also associated with cleft lip, cleft palate, or cleft lip with or without cleft palate and follows autosomal dominant inheritance

Answer 7

Van der Woude syndrome (VWS)

Question 8

______ are a group of inherited disorders that typically affect the skin, hair, sweat glands, and teeth.

Answer 8

Ectodermal dysplasias (ED). There are over 150 ectodermal dysplasias that have numerous inheritance patterns. While there are autosomal dominant forms of EDs, they are not commonly known to cause clefting or lower lip pits.

Question 9

______ is also known as craniofacial microsomia and oculo-auriculo-vertebral spectrum. This is a spectrum of malformations that include facial asymmetry, hypoplastic mandible, preauricular/facial tags, ear malformations, and hearing loss.

Answer 9

Goldenhar syndrome. While craniofacial anomalies including cleft lip and/or palate can be seen in this condition, lower lip pits are not a prominent feature.

Question 10

In 21-hydroxylase deficiency, there is a blockage in the conversion of 17-hydroxyprogesterone (an androgenic compound) to 11-deoxycorticol (a mineralocorticoid and aldosterone precursor). This leads to

Answer 10

androgen excess (and virilization) and mineralocorticoid and glucocorticoid deficiency of varying degrees.

Question 11

occurs 20 - 50 times more frequently in 47, XXY males than in 46, XY males. The other conditions listed do not occur more frequently in Klinefelter syndrome.

Answer 11

Breast cancer

Question 12

_____ is a form of primary or hypergonadotropic hypogonadism. As a result of decreased testosterone production, gonadotropins are elevated. Estrogen levels are also elevated.

Answer 12

Klinefelter syndrome

Question 13

_____ is the term used to describe variation in clinical features, in both type and severity, of a genetic disorder between different affected individuals, even within the same family. For example, neurofibromatosis type I can be highly variable in presentation.

Answer 13

Variable expressivity

Question 14

____ is the term used to describe a condition where some individuals express the condition while others do not, despite carrying a mutation in the disease-causing gene.

Answer 14

Incomplete penetrance

Question 15

_____ is the term used in clinical genetics to describe a single genetic condition that can result from different mutations in different genes. Noonan syndrome is an example of this phenomenon, as the same phenotype results from mutations in 6 different genes.

Answer 15

Locus heterogeneity

Question 16

______ refers to differing mutations within the same gene at the same chromosomal locus, resulting in a single phenotype. For example, cystic fibrosis can be caused by any of more than a thousand different mutations in the CFTR gene.

Answer 16

Allelic heterogeneity

Question 17

____ refers to multiple, often seemingly unrelated physical effects caused by a single altered gene or pair of genes.

Answer 17

Pleiotropy

Question 18

______ manifests with exophthalmos, craniosynostosis, mental retardation, hypertelorism, arachnodactyly, pectus excavatum, scoliosis, and joint laxity. There is no involvement of the heart. Rarely, aneurism of the sinus of Valsalva may be present

Answer 18

Shprintzen-Goldberg syndrome

Question 19

____ should be the first clue to suggest an autosomal recessive condition in this case.

Answer 19

Consanguinity. First cousins share 1/8 of their genes in common and are therefore more likely to carry the same autosomal recessive gene mutations. This increases the chance of having affected offspring. Evidence to further support autosomal recessive inheritance is that the males and females appear equally affected and there is no vertical transmission.

Question 20

Lethal forms of autosomal dominant conditions are typically due to spontaneous new mutations that occur in a particular gene at the time of conception. In the case of new mutations, there is no family history and the parents are unaffected.

Answer 20

The recurrence risk is considered low, approximately 2%. This residual risk remains due to the possibility of gonadal mosaicism, meaning that the mutation is present only in some of the germ cells of a parent.

Question 21

______ is characterized by short stature with disproportionate short limbs, limited elbow extension, trident hands, thoracolumbar gibbus, and lumbar lordosis. Characteristic facial features include frontal bossing, depressed nasal bridge, and midface hypoplasia. The most distinctive radiographic findings are narrowing of the interpediculate distance of the caudal spine, notch-like sacroiliac groove, squared iliac wings, circumflex or chevron seat on the metaphysic, and metaphyseal flaring/cupping.

Answer 21

Achondroplasia

Question 22

_____ is a type of short-limbed dwarfism that is typically associated with perinatal lethality due to respiratory compromise. Features include micromelia, cloverleaf skull, short ribs, narrow thorax, macrocephaly, brachydactyly, and redundant skin folds. There are 2 types that are easily distinguished by the radiographic features of the femurs. Type I has bowed femurs, and while in type II, they are straight.

Answer 22

Thanatophoric dysplasia (TD). While trident hands, frontal bossing, and depressed nasal bridge are features shared by both TD and achondroplasia, the patient has no rib or thorax anomalies. In addition, the patient has alternative radiographic findings that are inconsistent with those of TD.

Question 23

General characteristics of _____ include hypotrichosis, hypohidrosis, and hypodontia. Scalp hair is thin, lightly pigmented, and slow-growing. Sweating is greatly diminished, resulting in episodes of hyperthermia. Eruption of deciduous teeth is delayed. Teeth can be abnormally formed, small, and often conical. Physical growth and psychomotor development are otherwise within normal limits.

Answer 23

Ectodermal Dysplasias (ED).

Question 24

_______ represents a group of mesodermal dysplasia defects affecting the tooth enamel. Enamel can be hypoplastic, hypocalcified, hypomineralized, and immature in development. Teeth can be unusually small, discolored grooved, or pitted and brittle. The defect in AI is isolated to the enamel with no other ectodermal anomalies.

Answer 24

Amelogenesis imperfecta (AI)

Question 25

represents a group of disorders characterized by brittle, discolored, and translucent teeth. Isolated DI does not involve other systemic findings.

Answer 25

Dentinogenesis imperfecta (DI)

Question 26

______ is a group of disorders characterized by a lack of melanin in the skin, hair, and eyes. Nystagmus, strabismus, reduced iris pigment and translucency, foveal hypoplasia, and reduced visual acuity are common features.

Answer 26

Oculocutaneous albinism (OCA). Other ectodermal issues such as hypohidrosis, oligodontia and nail dysplasia are not associated with OCA.

Question 27

_____ is an overgrowth syndrome with a distinct phenotype. It is not obvious at birth, and there are no specialized laboratory tests that can confirm a diagnosis. Rapid growth occurs in the 1st 5 years of life. At the same time, motor skills and cognitive development are delayed. Hypotonia is present as well.

Answer 27

Sotos syndrome, The phenotype includes a large head with a tall narrow skull; eyes that are wide set and downward slanting; a flat nose, pointed chin, and ‘receding hairline’; advanced bone age; as well as large hands and feet.

Question 28

The most appropriate step for prevention of spread of meningococcal infection to other contacts is to _______.
It is reported that 50% of all meningococcal infection occurs in children below 2 years of age. Another 25% of cases occur in people above 30 years of age. An increased incidence is observed in young persons between 15 to 19 years of age, especially fresh college entrants living in dormitories.

Answer 28

administer rifampicin prophylaxis to all children and adults in the same household or daycare irrespective of their immunization status.

Question 29

The face is shaped as an inverted triangle - prominent forehead, deep-set eyes, moderate hypertelorism, pointed chin and straight nose with a bulbous tip. Liver problems are usually observed within the first three months of life, and include cholestasis, jaundice, pruritus and paucity of bile ducts. Heart problems range from murmur to peripheral or pulmonic stenosis or tetralogy of Fallot. Skeletal and ophthalmologic abnormalities do not usually cause medical problems, but can aid in diagnosis. They include butterfly vertebrae and posterior embryotoxon.

Answer 29

Alagille syndrome is a genetic disorder inherited in an autosomal dominant fashion. It is caused by mutations in the JAG1 gene, localized to chromosome 20p12. It is characterized by liver, heart, skeletal, and ophthalmologic abnormalities.Diagnosis is based on clinical findings, although deletion studies are available clinically. Direct mutation analysis is available on a research basis only. These individuals also tend to show pancreatic insufficiency and growth failure.

Question 30

Patients share a common phenotype that includes mild mental retardation, cardiovascular disease, connective tissue abnormalities and a distinctive facies. Connective tissue abnormalities include joint laxity, loose skin, hoarse voice and tendency for hernia. Affected individuals usually have bitemporal narrowing, periorbital fullness, a short nose with a bulbous tip, malar hypoplasia, long philtrum, full lips, wide mouth with a small lower jaw and prominent earlobes. Teeth tend to be small and widely spaced.

Answer 30

William’s syndrome is a microdeletion syndrome caused by a contiguous gene deletion of a critical region on chromosome 7q11. The most common cardiac finding is supravalvar aortic stenosis. Personality is unique in that affected individuals tend to be overly friendly, anxious, and have attention deficit disorder. Growth pattern shows prenatal growth deficiency, failure to thrive in the first four years and a brief pubertal spurt. Average height as an adult is less than the third percentile.

Question 31

Symptoms include hypoglycemia, jaundice, failure to thrive, vomiting and sepsis. It is a progressive disorder if not diagnosed and treated, eventually leading to mental retardation and death.

Answer 31

Galactosemia is an autosomal recessive disorder of carbohydrate metabolism. included in newborn screening a

Question 32

most common symptoms seen in 22q11-deletion syndrome include

Answer 32

congenital heart disease (particularly conotruncal malformations), palatal abnormalities, hypocalcemia, immune deficiency, characteristic facial features and learning difficulties.

Question 33

____ is an accelerated growth disorder of unknown etiology characterized by a distinct facial appearance; a low-pitched and hoarse cry; as well as hypertonia. Also present are psychomotor delay; loose skin and umbilical; as well as inguinal hernias. Excessive growth is seen in early infancy in all cases, and prenatally in most.

Answer 33

Weaver syndrome. Characteristic facial features include micrognathia with a distinctive dimpled chin; hypertelorism; large and low-set ears; as well as telecanthus.

Question 34

____ is an overgrowth syndrome with a distinct phenotype. It is not obvious at birth and there are no specialized laboratory tests that can confirm a diagnosis. Rapid growth occurs in the 1st 5 years of life. At the same time, motor skills and cognitive development are delayed. Hypotonia is present as well.

Answer 34

Sotos syndrome. The phenotype includes a large head with a tall narrow skull; eyes that are wide set and downward slanting; a flat nose, pointed chin, and ‘receding hairline’; advanced bone age; as well as large hands and feet.

Question 35

______ because the mother is diabetic and had poor glycemic control during pregnancy. It produces ventricular outflow obstruction resulting in cardiomegaly and congestive heart failure. Cardiac output decreases as the thickness of the septum increases. Most symptoms resolve by 2 weeks of age and septal hypertrophy clears by the age of 4 months.

Answer 35

Asymmetric ventricular septal hypertrophy (AVSH), Diagnosis is confirmed by echocardiography, which shows hypertrophy of the interventricular septum, the right ventricular anterior wall, and left ventricular posterior wall.Propranolol is the drug of choice for its treatment. Ionotropic drugs are contraindicated as they worsen the obstruction.

Question 36

30% of infants of diabetic mothers have _____ and 5-10% have _______

Answer 36

cardiomegaly and congestive heart failure.

Question 37

The FDA has approved the use of in children with Prader-Willi syndrome based on the observation that it increases lean body mass and strength. It also decreases fat mass; therefore, it can improve the quality of life for these children.

Answer 37

growth hormone

Question 38

Obesity is fairly common in achondroplasia and worsens lumbar lordosis, leading to a higher cardiac morbidity. ______ and ______ are also exacerbated by obesity.

Answer 38

Degenerative joint disease and upper airway obstruction. Early dietary consultation is recommended to help avoid these complications.

Question 39

_____ is the most useful agent for management of left ventricular outflow obstruction due to asymmetric ventricular septal hypertrophy. Infant may present with cardiomegaly, heart failure, and poor cardiac output. Cardiac output decreases with increasing septal thickness.

Answer 39

Propranolol

Question 40

The neural tube closes between the

Answer 40

23rd and 28th day of gestation, corresponding to 3 to 4 weeks post-conception.

Question 41

First-cousins share 1/8 of their genes in common. Couples who are first-cousins have a _____ increased risk above the 2-3% general population risk of adverse fetal outcome for an overall risk of approximately.

Answer 41

1.7 to 2.8%.

5%.

However, the risk may be as high as 25% in the context of a family history suggestive of an autosomal recessive condition

Question 42

In a 45,X female, no Barr bodies will be seen on buccal smear; however, this test is not useful for other varieties of Turner syndrome. definitive diagnosis _______

Answer 42

Chromosome analysis will definitively diagnose Turner syndrome, which most commonly is caused by a 45,X pattern, but also by subtotal deletions of one X chromosome.

Question 43

A Caucasian female infant has a positive newborn screen for cystic fibrosis. Genetic testing has identified a mutation in each of the patient’s CFTR genes. Parental studies confirmed that the patient’s mother and father are each carriers. The couple is concerned about their two other children and their risks of being carriers of cystic fibrosis.
What is the risk to this patient’s unaffected siblings to be cystic fibrosis carriers?

Answer 43

2 in 3

Question 44

identifies 99% of cases that are due to deletions, uniparental disomy, and imprinting center defects. While this testing has 99% sensitivity, the result cannot indicate the underlying molecular mechanism for the diagnosis in a particular individual. Additional molecular testing is required to delineate the specific underlying molecular anomaly.

Answer 44

Prader-Willi methylation analysis

Question 45

The finding of a low grade of aortic regurgitation in an asymptomatic patient with a likely diagnosis of Marfan syndrome does not preclude athletic participation, but warrants

Answer 45

follow-up for progression of aortic regurgitation and evidence of aortic root dilatation.

Question 46

, as the infant has micrognathia (hypoplastic lower jaw) and high arched palate, which are the typical features of this syndrome. As a result, the tongue falls back in the throat, causing difficulty in breathing due to obstruction of the airway. Since the jaw is very small, the tongue appears large. Other features include the presence of natal teeth and cleft palate.

Answer 46

Pierre Robin syndrome