Paediatrics - Genetics

Front 1

Define:

• Malformation

• Deformation

• Disruption

• Dysplasia

Back 1

• Primary structural defect occurring during the development of a tissue or organ, eg cleft palate

• Abnormal intrauterine mechanical forces that distort a normally formed structure

• Disruption - destruction of a fetal part which was initially formed normally eg amniotic bands causing limb reductions

• Abnormal cellular organisation or function of a specific tissue type, eg skeletal dysplasia

Front 2

Define:

• Sequence

• Association

• Syndrome

(in relation to dysmorpholgy and birth defects)

Back 2

• A pattern of multiple abnormalities that occur after 1 initial defect. Eg oligohydramnious causing fetal compression and pulmonary hypoplasia, caused by renal agenesis - Potter syndrome)

• A group of malformations that occur together more often than expected by chance, but in different combinations eg VACTERL (Vetebral anomalies, Anal atresia, Cardiac defects, TracheoEsophageal fistula, Renal abnormalities and radial Limb defects)

• A particular set of multiple abnormalities occur repeatedly in a constant pattern, often there is known to be / thought to be an underlying causative mechanism eg Down's

Front 3

What are the 3 methods through which Down's syndrome occurs?

Back 3

• Meiotic non-dysjunction (94%)

• Robersonian translocation (5%)

• Mosaicim (1%)

Front 4

What are some typical dysmorphic features associated with Down's syndrome?

Back 4

Round face

Flat nasal bridge

Upslanted palpebral fissures

Epicanthic folds

Brushfield spots

Macroglossia

Small ears

Flat occiput

3rd fontanelle

Short neck

Single palmar crease

Hypotonia

Front 5

What congenital conditions is Down's syndrome associated with?

Back 5

• Congenital heart defects - AVSD, VSD, ToF, Mitral valve prolapse

• Duodenal atresia

• Hirshprung's

Front 6

When and how is Down's syndrome screened for?

Back 6

• 10-14 weeks - Combined test - Nuchal translucency, betaHCG, PAPP

• 15-20 weeks - Quad test - betaHCG, alpha fetoprotein, inhibin A, estriol

• Amniocentesis or chorionic villous sampling - 15 weeks onwards

Front 7

What is the cause of Edward's syndrome?

What are some associated features?

Back 7

• Trisomy 18 (non-dysjunction or Robersonian translocation)

• Kidney malformations, structural heart defects, respiratory difficulties, apnoea, omphalocele, intellectual disability

Front 8

What is the cause of Patau's syndrome?

What are some associated features?

Back 8

• Trisomy 13 (non-dysjunction, Robersonian translocation, or mosaicism)

• IUGR, congenital heart defects (AVSD, dextrocardia), holoprosencephaly, neural tube defects, microcephaly, seizures, polycystic kidneys

Front 9

What is Fragile X syndrome?

Back 9

Severe learning disability in males due to a trinucelotide repeat mutation on the fragile X mental retardation gene FMR1

Front 10

What is the genetic inheritance of Noonan syndrome?

Back 10

Autosomal dominant (chr12, 2, or 3)

Front 11

What are the 2 genetic variations in Turners syndrome?

Back 11

True 45X karyotype, or 45X with deletion of the short arm of the "absent" X chr

Front 12

How would someone with Turner's syndrome typically look?

Back 12

Short stature, broad chest, widely spaced nipples, wide carrying angle, webbed neck

Front 13

Which CV defect is most commonly seen in Turner's syndrome?

Back 13

Coarctation or the aorta

Front 14

What is the genetic karyotype of someone with Klinefelter's syndrome?

What might be seen on microscopy of their cells?

Back 14

• 47XXY (other variants exist eg 48XXXY)

• Barr's bodies - dense chromatin mass made from the extra chromosome

Front 15

How might someone with Klinefelter's typically appear?

Back 15

Tall, slender, lack of facial or pubic hair, hypogonadotrophic hypogonadism, gynaecomastia, learning difficulties

Front 16

Give some example diseases for:

• Autosomal dominant

• Autosomal recessive

• X linked

Back 16

• Achondroplasia, ADPKD, Huntington's, Marfan's

• CF, sickle cell anaemia, congenital adrenal hyperplasia

• Duchenne's MD, haemophilia, hypophosphataemic rickets

Front 17

Define:

• Uniparental disomy

• Heterodisomy

• Isodisomy

Back 17

• When a person receives 2 copies of one chromosome from one of their parents and no copies from the other parent

• A pair of non-identical chromosomes from one parent (meiosis I error)

• A single chromosome from one parent is inherited and then duplicated (meiosis II error)

Front 18

Give an example of 2 imprinting disorders that are caused by uniparental disomy

Back 18

• Prader-Willi syndrome - The individual has 2 copies of chr15 from their mother, and no chr15 from their father.

• Angelman syndrome - The individual has 2 copies of chr15 from their father, and none from their mother

Front 19

What occurs when there is unpiarental disomy of ALL the chromosomes?

Back 19

Molar pregnancy - Complete = diploid (2 sets of paternal chromosomes). Partial = triploid (2 sets of paternal + 1 set of maternal chromosomes)

Front 20

How can genetic disorders be investigated (genetic/DNA analysis)?

Back 20

• Polymerase chain reaction (PCR)

• Karyotyping (cytogenetic analysis)

• Microassay comparative genetic hybridisation (aCGH)

• Fluorescent in-situ hybridisation (FISH)