Genetics

Question 1

Leukemia associated with DS

Answer 1

Acute lymphocytic leukemia (but acute myeloblastic leukemia if in first 3 years of life)

Question 2

Natural Hx of DS

Answer 2

– Major cause for early mortality is congenital heart disease
– Muscle tone improves with age
– Rate of development slows with age
– Early onset of Alzheimer disease

Question 3

______is the second most common pattern of human malformation.

Answer 3

Edwards syndrome

Question 4

SSx of Edwards syndrome

Answer 4

– Mental retardation
– Low-set, malformed ears; microcephaly, micrognathia; prominent occiput
– Clenched hand—index over third; fifth over fourth

Question 5

Cardiac abn associated with Edwards

Answer 5

– VSD, ASD, PDA, cyanotic lesions,

Question 6

Ortho abn associated with Edwards

Answer 6

– Rocker-bottom feet, hammer toe

Question 7

GI abn associated with Edwards

Answer 7

– Omphalocele

Question 8

Natural Hx of Edwards

Answer 8

– Many spontaneous abortions
– Feeble from birth
– Most do not survive first year

Question 9

defect of midface, eye, and forebrain development → single defect in first 3 weeks’ development of prechordal mesoderm. It involves older maternal age

Answer 9

Patau syndrome

Question 10

Asscn with Patau

Answer 10

– Scalp defects in parietal-occipital area (cutis aplasia)

– Postaxial polydactyly

Question 11

Deletion asstd with WAGR syndrome

Answer 11

11p13; Wilms + Aniridia + GU anomalies + MR

Question 12

– Decreased IQ (average IQ 85−90)
– Behavioral/psychiatric problems
– Long limbs (decreased upper:lower segment ratio)

Answer 12

Klinefelter Syndrome (XXY)

Question 13

– Congenital lymphedema, residual puffiness over dorsum of fingers and toes
– Broad chest, wide-spaced nipples
– Low posterior hairline; webbed posterior neck
– Cubitus valgus (elbow) and other joint problems
– Horseshoe kidney, and other renal defects

Answer 13

Turner Syndrome (XO)

Question 14

MC cardiac abn asstd with Turner

Answer 14

° Bicuspid aortic valve (number 1 cardiac anomaly)

° Coarctation

Question 15

Natural Hx of Turner

Answer 15

– Decreased height velocity with delayed bone age
– Estrogen treatment indicated
– May increase height by 3−4 cm with growth hormone (GH)

Question 16

Fragile X syndrome

Fragile site on _________in affected males and some carrier females—

Molecular diagnosis—variable number of repeat ______(preferred diagnosis = DNA-based molecular analysis)

Answer 16

long arm of X

CGG

Question 17

Features of Fragile X

Answer 17

– Mild to profound mental retardation; learning problems
– Large ears, dysmorphic facial features, large jaw, long face
– Large testes—mostly in puberty (macroorchidism)(fertile

Question 18

Genetic abn in Beckwith-Wiedemann Syndrome

Answer 18

– IGF-2 disrupted at 11p15.5 (imprinted segment)

Question 19

Findings of Beckwith-Wiedemann Syndrome

Answer 19

– Macrosomia
– Macroglossia—may need partial glossectomy
– Pancreatic beta cell hyperplasia—excess islets → hypoglycemia

Question 20

What dxtic test to do in pts with Beckwith-Wiedemann Syndrome

Answer 20

obtain ultrasounds and serum AFP every 6 months through 6 years of age to look for Wilms tumor and hepatoblastoma

Question 21

– Most with deletion at 15q11-q13–imprinted segment

– Paternal chromosome responsible

Answer 21

Prader-Willi Syndrome

Question 22

Prader-Willi Syndrome features

Answer 22

– Obesity—onset from 6 months to 6 years
– Mild to severe mental retardation
– Food-related behavioral problems (binge eating)
– Small hands and feet, puffy; small genitalia
– Hypothalamic—pituitary dysfunction (growth, thyroid, adrenal)

Question 23

– Severe MR
– Paroxysms of inappropriate laughter
– Absent speech or <6 words (100%); most can communicate with sign language

Answer 23

Angelman Syndrome (Happy Puppet Syndrome)

Question 24

Why is Angelman Syndrome called Happy Puppet Syndrome)

Answer 24

Ataxia and jerky arm movements resembling a puppet’s movements (100%)

Question 25

Mandibular hypoplasia in utero → posteriorly placed tongue → posterior palatal, shelves → cleft palate and other palatal abnormalities

Answer 25

Robin Sequence (Pierre Robin

Question 26

Isolated finding or associated with some syndromes of Robin Sequence (Pierre Robin)

Answer 26

fetal alcohol syndrome, Edwards Syndrome

Question 27

Findings in Robin Sequence (Pierre Robin

Answer 27

– Micrognathia – Retroglossia → possible airway obstruction – Cleft soft palate and other abnormalities

Question 28

Mutations in gene for fibroblast growth factor receptor 3 at 4p16.3 (FGFR3)

Answer 28

Achondroplasia/Hypochondroplasia

Question 29

FIndings in Achondroplasia/Hypochondroplasia

Answer 29

– Short stature (increased upper-to-lower segment ratio; short-limbed dwarfism) – Proximal femur shortening – Megalocephaly, small foramen magnum (may have hydrocephalus), small cranial base, prominent forehead – Lumbar lordosis

Question 30

Cx of Achondroplasia/Hypochondroplasia

Answer 30

Early cervical compression, respiratory problems, obstructive and central apnea, later cardiovascular disease

Question 31

– Autosomal dominant with wide variability | – Mutation in fibrillin gene (FBN1)—15q21.1

Answer 31

Marfan Syndrome

Question 32

Bony abn asstd with Marfan

Answer 32

``` – Arm span > height – Arachnodactyly – Decreased U:L segment ratio (as with XXY) – Joint laxity with kyphoscoliosis – Pectus excavatum or carinatum ```

Question 33

Ophtha abn asstd with MArfan

Answer 33

Lens subluxation (upward; defect in suspensory ligament); secondary glaucoma, myopia, retinal detachment

Question 34

Cardiac abn asstd with MArfan

Answer 34

Ascending aortic dilatation with or without dissecting aneurysm (uncommon in children and adolescents unless case is severe) with secondary aortic regurgitation. Mitral valve disease (MVP and regurgitation) is the most common in children.

Question 35

NAtural course of Marfan

Answer 35

– Prevent scoliosis – Vascular complications chief cause of death – Evaluate heart and aorta

Question 36

– Droopy ears – Hyperextensible skin, fragile, easy bruisability, poor wound healing – Joint hyperlaxity; tendency toward hip, shoulder, knee, and clavicular dislocation

Answer 36

Ehlers-Danlos Syndrome

Question 37

Ehlers-Danlos Syndrome cardiac association

Answer 37

– MVP, tricuspid valve prolapse, aortic root dilatation; dissecting aneurysm, ASD

Question 38

Ophtha findings of Ehlers-Danlos Syndrome

Answer 38

Blue sclera, myopia, glaucoma, ectopia lentis, retinal detachment

Question 39

Cardiac anomalies in EDS:

Answer 39

VSD > ASD, tetralogy of Fallot

Question 40

• Similar features with prenatal exposure to carbamazepine, valproate, primidone, and phenobarbital • No dose-response relationship has been demonstrated • Growth deficiency

Answer 40

Fetal Hydantoin Syndrome

Question 41

Physical features of Fetal Hydantoin Syndrome

Answer 41

Hirsutism | • Cupid’s-bow lips

Question 42

* Midface hypoplasia; cleft lip * Cardiac defects * Long, thin fingers and toes; convex nails * Meningomyelocele

Answer 42

Fetal Valproate Syndrome

Question 43

* Mild facial asymmetry; bilateral microtia/anotia (ear); facial nerve paralysis ipsilateral to ear; narrow, sloping forehead; abnormal mottling of teeth * Conotruncal malformations * CNS malformations

Answer 43

Retinoic Acid Embryopathy (from Isotretinoin)

Question 44

Upto when is taking (from Isotretinoin) safe?

Answer 44

No problems if stopped before 15th postmenstrual day

Question 45

– Renal agenesis/dysgenesis or other type of urinary tract defect must occur prior to 31 days’ gestation → oligohydramnios (also from chronic leakage) – Leads to fetal compression (mid-face, ears) – Lack of alveolar sac development → pulmonary hypoplasia

Answer 45

Potter Sequence

Question 46

What is the Potter facies

Answer 46

hypertelorism, epicanthal folds, low-set flattened ears, micrognathia, compressed flat nose

Question 47

VACTERL Association

Answer 47

``` V = Vertebral defects A = Anal atresia (imperforate anus) C = Cardiac defects (VSD and others) T = TE fistula E = Esophageal atresia R = Renal defects L = Limb defects (radial ```

Question 48

CHARGE Association

Answer 48

``` C = Coloboma (from isolated iris to anophthalmos; retinal most common) H = Heart defects (TOF, PDA, and others) A = Atresia choanae R = Retardation of growth and/or development G = Genital hypoplasia (in males) E = Ear anomalies and/or deafness ```