Genetics

Question 1

Why do mitochondrial diseases have a large degree of phenotypic variability

Answer 1

Heteroplasmy, which means that within one cell may have different ratios of normal and mutated mitochondrial DNA

Question 2

Camptodactyly (flexion of proximal interphalangeal joint), thick lips, deep set eyes, prominent cupped ears, mild to severe mental deficiency, pelvic or hip dysplasia, uteral-renal anomalies

Answer 2

Trisomy 8 (rare, majority are mosaic since complete is lethal in utero)

Question 3

Midline abnormalities, cardiac (vsd>pda), cutis aplasia, narrow hyper convex fingernails, cleft lip, small eyes, microcephaly or holoprosencephaly, persistence of fetal hemoglobin, increased neutrophils with nuclear projections

Answer 3

Trisomy 13 (1 in 5-10,000 live births)

Question 4

Cardiac in 95-99% of patients (VSD, pda>bicuspid aortic valve, pulm stenosis, tof), clenching hands with overlapping digits, rocker bottom feet, small mouth, short sternum

Answer 4

Trisomy 18 (1 in 6000), females > males (3:1)

Question 5

Endocardial cushion defects, hypothyroidism, hyperflexibility of joints, 5th finger with hypoplastic middle phalanx and clinidactyly, up slanting palpebral fissures, brushfield spots, pelvic dysplasia, transient myeloproliferitive disorder

Answer 5

Trisomy 21 (1 in 800)

Question 6

Cardiac (30%) (VSD, pda, tof), transverse palmar crease, downslantint palpebral fissures, hypertelorism, mental deficiency, microcephaly, failure to thrive

Answer 6

Cri-du-chat (deletion 5p syndrome); partial deletion of short arm of the 5th chromosome (deleted portion is paternal origin in 80% of de novo), majority are de novo

Question 7

Thumb hypoplasia, colobomas, increased risk of retinoblastoma, microcephaly, high nasal bridge, hypertelorism, epicanthal fold, microcephaly, IUGR, focal lumbar agenesis

Answer 7

Deletion 13q syndrome

Question 8

High forehead, broad or beaked nose, hypertelorism, low set simple eat with lreauricular dimple, supraordbital ridge continuous with nasal bridge, microcephaly, severe cognitive deficits, seizures

Answer 8

Deletion 4p syndrome (wolf-hirschhorn syndrome) 87% de novo mutations

Question 9

22q11.2 microdeletion syndrome

Answer 9

CATCH-22 (cardiac, abnormal facies, thymus hypoplasia, cleft palate, hypoglycemia)
Secondary to a defect in the 4th brachial arch and derivatives of the 3rd and 4th pharyngeal pouches
Most common chromosomal deletion in humans

Question 10

Broad thumbs and first toes, downslanting palpebral fissures, hypoplastic maxilla, narrow palette, prominent and or beaked nose, microcephaly, cryptorchidism, postnatal growth deficiency, increased risk of tumors

Answer 10

Rubinstein-Taybi syndrome
16q13.3 deletion, which encodes the cAMP-regulated enhancer-binding protein

Question 11

WAGR syndrome

Answer 11

11p13 deletion
Wilms tumor (50%), aniridia, GU abnormalities (cryptorchidism, hypospadias), retardation

Question 12

Supravalvar aortic stenosis, peripheral pulmonic stenosis, hypoplastic nails, prominent lips, hoarse voice, blue eyes, stellar iris pattern, short palpebral fissures, epicanthal folds, long philtrum, mental deficiency, hypercalcemia (usually transient)

Answer 12

Williams syndrome
7q11.23 deletion leading to deletion of an elastin gene

Question 13

Cardiac (50%): pda, VSD, asd; polydactyly, syndactyly (feet), lateral displacement of inner canthis, corneal opacity, brachycephaly

Answer 13

Carpenter syndrome, Autosomal recessive

Question 14

Cardiac (60%): single atrium or asd; short distal extremities, polydactyly (fingers more than toes), nail hypoplasia, delayed tooth eruption, narrow thorax, typically normal intelligence but 50% mortality during infancy due to cardio respiratory difficulties

Answer 14

Ellis-van crevald syndrome, autosomal recessive, chondroectodermal dysplasia

Question 15

Hyperpigmentation, radial hypoplasia, thumb hypoplasia, renal and GU abnormalities, pancytopenia, increased risk of AML

Answer 15

Fanconi pancytopenia syndrome, autosomal recessive, increased number of chromosomal breaks (requires a breakage study to assess)

Question 16

Genetics of Meckel-Grubwr syndrome

Answer 16

Autosomal recessive, locus mapped to 17q21-24

Question 17

Polydactlyly, occipital encephalocele, cystic dysplastic kidneys, bile duct proliferation, hepatic cysts, microphathalmia, cleft palate, micrognathia, cryptorchidism

Answer 17

Meckel-Gruber Syndrome

Question 18

Encephalocele, hypertelorism, widely set nostrils, anterior cranium bifidum occultum

Answer 18

Frontonasal dysplasia

Question 19

Encephalocele, eye abnormalities (microphthalmia, cataracts), CNS anomalies (ventriculomegaly, midline abnormalities, lissencephaly)

Answer 19

Walker-Warburg Syndrome

Question 20

Genetics and cause of Smith-Lemli-Opitz syndrome

Answer 20

Autosomal recessive, defect in cholesterol synthesis, lead to low cholesterol levels and elevated precursor (7-dehydrocholesterol) levels

Question 21

Second and 3rd toe syndactlyly, ptosis, cataracts, low set or slanted ears, anteverted nostrils, hypogenitalia, hypospadias, microcephaly, moderate to severe mental deficiency

Answer 21

Smith-lemli-opitz

Question 22

Thrombocytopenia, granulocytosis, eosinophilia, anemia, absent bilateral radii, thumbs always present, ulnar abnormalities, hip dysplasia, cardiac (30%): tof, asd

Answer 22

TAR (thrombocytopenia-radial aplasia) syndrome

Question 23

CDH, agensis or corpus callosum, dandy walker malformation, olfactory nerve abnormalities, optic hypoplasia, severe intellectual disability, coarse facial features, digital and nail hypoplasia

Answer 23

Fryns syndrome

Question 24

Most common inherited cause of mental deficiency

Answer 24

Fragile X syndrome

Question 25

Genetics of fragile X

Answer 25

X-linked dominant with 80% penetrance in males and 30% penetrance in females

Question 26

Long facies, prominent forehead, large ears, large testies post puberty, mental deficiency, autism, hyper extensible fingers or joints, mild connective tissue dysplasia

Answer 26

Fragile x syndrome

Question 27

Genetics of menkes syndrome

Answer 27

X-linked recessive, gene located at xq13

Question 28

Risk in patients 45x/46xy

Answer 28

Increased risk of residual gonadal tissue that can lead to granadoblastoma so the recommendation is for exploratory laparotomy during childhood to remove this tissue

Question 29

Cause of charge syndrome

Answer 29

Mutation in chromodomain helicase dna-binding gene 7 (chd7) on chromosome 8q12 that leads to altered chromatin; autosomal dominant but majority are de novo

Question 30

Symptoms of charge syndrome

Answer 30

Coloboma, heart defects, atresia of the choanae, restricted growth, genital hypoplasia, and ear anomalies

(Major criteria: ear, cranial nerve abnormalities, coloboma, choanal atresia)

Question 31

Genetics and cause of Schwachman-Diamond syndrome

Answer 31

Autosomal recessive, 90% are associated with mutation in SDS gene on chromosome 7q11, which plays an important role in the maturation of the 60 S ribosomal sub unit and ribosomal assembly

Question 32

Bone marrow failure (neutropenia most common, anemia, thrombocytopenia), pancreatic dysfunction, recurrent infections, skeletal abnormalities

Answer 32

Schwachman Diamond syndrome

Question 33

3rd and 4th finger syndactyly, add/vsd, brain abnormalities, large placenta with hydatiform changes, IUGR

Answer 33

Triploidy

Question 34

Micronesia, synophrys, thin down-turning upper lip, long and curly eyelashes, mental deficiency, initial hypertonicity, microbrachycephaly, hirsuitism, low posterior hairline, cutis marmorata

Answer 34

Cornelia de Lange syndrome

Question 35

Expressionless facies, micrognathia, talipes equinovarus

Answer 35

Mobius sequence

Question 36

Cause if goldenhaar syndrome

Answer 36

Due to 1st and 2nd brachial arch abnormalities

Question 37

Vsd, short neck, low posterior hairline, limited movement of head, deafness, abnormal cervical vertebrae, can be associated with Sprengel deformity (failure of scapula to descend to normal location leading to elevation and medial rotation of inferior portion of scapula)

Answer 37

Klippel-Feil sequence

Question 38

Asymmetric limb hypertrophy, vascular lesions

Answer 38

Klippel-Trenaunay-Weber

Question 39

Unilateral hypoplasia or absence of pectoralis muscle, various renal anomalies, rib anomalies, may have hemivertibrae

Answer 39

Poland sequence

Question 40

Small triangular facies, downturning corners of mouth, short stature, congenital asymmetry of skeleton, hypoglycemia, 5th finger clinidactyly, excess sweating of head and upper trunk in infancy, cafe au lair spots, large and late closing fontanels

Answer 40

Russell silver syndrome

Question 41

Vacterl

Answer 41

Vertebral anomalies, anorectal malformation, cardiac (vsd > tof, coarct), TE fistula, renal anomaly, limb anomaly

Question 42

Imperforate anus, dysplastic ears, thumb anomalies

Answer 42

Townes-Brock’s syndrome

Question 43

Inheritance of Beckwith-Wiedemann

Answer 43

50% are due to loss of methylation on the maternal chromosome 11, 20% are due to paternal uniparental disomy, 5% are due to gain of methylation on maternal chromosome 11

Question 44

Port wine stains, and underlying spinal angiomas

Answer 44

Cobb syndrome, also known as cutaneomeningoapinalangiomatosis

Question 45

Management of a sebaceous Nevis, and why

Answer 45

Excision in childhood, because of risk of progression to malignancy and later life

Question 46

Location of Bohn nodules versus Ebstein pearls

Answer 46

Bohn nodules are located on the maxillary alveolar ridge, while Ebstein pearls are located on the hard palette

Question 47

Genetics of Leigh syndrome

Answer 47

Mitochondrial

Question 48

Cafe au lait macules, axillary freckling, maxillary freckling, macrocephaly, and learning disabilities

Answer 48

Legius syndrome, autosomal dominant mutation in spred1 gene

Question 49

Symptoms of Aicardi syndrome

Answer 49

Agenesis of the corpus callosum with polymicrogyria, ocular abnormalities, hemivertibrae, and seizure

Question 50

Chorioretinal lacunae are pathognomonic for:

Answer 50

Aicardi syndrome

Question 51

Noonan’s syndrome is associated with what developmental problem

Answer 51

Language impairments

Question 52

Inheritance pattern of Noonan syndrome

Answer 52

Autosomal dominant with complete penetrance but variable expression

Question 53

A family history of fatal disease in male infants with severe diarrhea and dermatitis suggests

Answer 53

IPEX (immune dysrgulation, polyendocrinopathy, enteropathy, x-linked syndrome)

Question 54

Upper eyelid coloboma associated with:

Answer 54

Goldenhaar syndrome

Question 55

Lower eyelid coloboma associated with:

Answer 55

Treacher Collins

Question 56

Is coloboma more common in upper or lower eyelid?

Answer 56

Upper

Question 57

TAPVR or persistent left SVC, downslanting palpebral fissures, anal atresia, coloboma of iris, renal agenesis

Answer 57

Cat-eye syndrome, extra part of chromosome 22 (either in quadruplicate or triplicate)

Question 58

Inheritance pattern and histopathology in congenital ichthyosiform erythroderma

Answer 58

Autosomal recessive
Increased stratum corneum AND increased granular layer

Question 59

Secondary features of x-linked ichthyosis

Answer 59

Cryptorchidism in 1/4 of males, increased incidence of corneal opacities, female carriers with this deficiency often have low estradiol excretion and difficult labor