Genetics

Question 1

What is the most likely diagnosis for pt presenting with tall, thin body habitus, pectus deformity, scoliosis, thin flat feet, long fingers with joint hypermobility, ectopia lentis, and family history of aortic disorder?

Answer 1

Marfan’s syndrome

Question 2

what is the likely diagnosis in a pt with Down’s syndrome who presents with whitish spots in ringlike configuration at the surface of the iris or speckled iris?

Answer 2

Brushfield spots

Question 3

What are the most common GI malformations seen in patients with Down Syndrome? (2)

Answer 3

1. Duodenal atresia (dilated loops of bowel with air fluid levels in duodenum, bilious vomiting)
2. Hirschsprung disease

Question 4

What is the most likely diagnosis for pt presenting with long eyelashes, thin brushed on eyebrows (can be unibrow), short nose with long thin philtrum, downturned upper lip (cupid’s bow), developmental delay, failure to thrive and Hirsutism?

Answer 4

Cornelia de Lange syndrome

Question 5

What musculoskeletal malformation is common in Down Syndrome patients?

Answer 5

Atlantoaxial subluxation

(signs of symptomatic spinal cord compression include neck pain, torticollis, gait abnormalities, loss of bowel/bladder control)

Question 6

What is the most likely genetic syndrome for patient presenting with small for gestational age, lymphedema of hands and feet, webbed neck (cystic hygroma on ultrasound), horseshoe kidney, widely spaced nipples, cubitus valgus deformity of elbow (wide carrying angle when extended), hyperconvex fingernails and low set hairline?

Answer 6

Turner syndrome

older age will have short stature, delayed sexual maturation and amenorrhea

Question 7

What are the 2 most common congenital heart defects associated with Turner’s syndrome?

Answer 7

1. Coarctation of aorta

2. Bicuspid aortic valve

Question 8

What pulmonary manifestation are patients with Marfan syndrome more likely to develop?

Answer 8

Spontaneous pneumothorax

collection of air between the visceral and parietal pleura leading to lung collapse

Question 9

What is the most likely diagnosis for pt presenting with growth retardation, palate deformity, hypernasal speech, conductive hearing loss, cryptorchidism, congenital heart defect (tetralogoy of Fallor, VSD), micrognathia, narrow palpebral fissures, prominent nose and long narrow face, and hypocalcemia?

Answer 9

Velocardiofacial syndrome

spectrum of Digeorge syndrome due to q11.2 microdeletion

Question 10

What is the most likely diagnosis for pt presenting with full face, broad forehead, flattened nasal bridge, rounded full cheeks like Elf, stellate patterned iris, supravalvular aortic stenosis (systolic ejection murmur at 1st right intercostal space with thrill), renal artery stenosis, HTN and very endearing, socially engaged and extremely polite personality?

Answer 10

Williams syndrome

dx: deletion of elastingene on 7q11.23

Question 11

What is the most likely diagnosis for pt presenting with developmental delays, frequent temper tantryms, obsessive picking at skin, weight above the 95th percentile, hypogonadism, and small hands?

Answer 11

Prader-Willi syndrome

(due to missing paternal 15q11 via microdeletion or methylation)

(history of profound neonatal hypotonia and poor feeding)

Question 12

What is the most likely diagnosis for pt presenting with cholestasis (direct hyperbilirubinemia, jaundice, elevated transminases), butterfly vertebrae, cardiac anomalies (peripheral pulmonic stenosis), pruritis, broad nasal bridge, deep set eyes and liver biopsy showing reduced number of bile ducts?

Answer 12

Alagille syndrome

(due to gene on chromosome 20)

(can have osteodystrophy, lipid abnormalities, and variceal bleeding)

Question 13

What is the likely diagnosis for pt presenting with seizures, hypertension and abdominal bruit (secondary to renal artery stenosis), axillary/inguinal freckling, scoliosis, hamartomas in iris, multiple bright spots on T2-weighted MRI and numerous oval macular light brownish-tan lesions on trunk?

Answer 13

Neurofibromatosis type 1 (NF 1, autosomal dominant)

(cafe-au-lait spots: 6 or more in prepuberty that are more than 5 mm in diameter)

(lisch nodules of iris)

Question 14

What is the most likely diagnosis for pt presenting with microcephaly, sloping forehead, lowset malformed ears, eye defect, scalp defect devoid of epidermis and dermis (aplasia cutis congenita- sharply demarcated ulcerated plaque covered by tense membrane), cleft palate, overlapping fingers and cryptorchidism?

Answer 14

Trisomy 13 (Patau) syndrome

(due to meiotic nondisjunction)

(mortality rate within 1st month is 80%)

Question 15

What is the most likely diagnosis for patient presenting with cleft lip/palate, external ear abnormalities, conductive hearing loss, malar hypoplasia, hypoplasia of zygomatic process, downward slanting palpebral fissures, colobomata of lateral 3rd of lower lid, and absence of eyelashes from medial 2/3 of lower eyelid?

Answer 15

Treacher-Collins syndrome

(mandibulofacial dysostosis)

(due to failure of neural crest cells due to mutation on chromosome 5)

Question 16

What is the most likely diagnosis for pt presenting with flattened occiput, protruding tongue, wide spaced teeth, wide mouth, easily excitable, frequent laughing/ smiling, hand flapping, tremulous limb movements, development delays and speech delay?

Answer 16

Angelman Syndrome

(due to loss of maternal 15q11)

(associated with seizures)

Question 17

What are the most common EKG changes associated with DiGeorge syndrome (microdeletion of 22q11.2)?

Answer 17

1. Prolonged QTc
2. prolonged ST

(due to hypocalcemia)

Question 18

What is the most likely diagnosis for pt presenting with 3 or more oval hypopigmented macules (usually on thigh or buttocks), facial angiofibromas in malar region of face, shagreen patch, seizures (infantile spasms), brownish fibrous plaques on forehead and yellowish orange connective tissue hamartoma?

Answer 18

Tuberous Sclerosis

autosomal dominant, gene degect on 9q (TSC1) or 16q (TSC2)

Question 19

what is the most likely diagnosis for male pt presenting with Autistic like features, developmental delay, intellectual disabilities, possible seizures, elongated face, broad forehead, prominent jaw and ears, strabismus, macroorchidism, and mitral valve prolapse?

Answer 19

Fragile X syndrome

due to more than 200 repeats of trinucleotide sequence in FMR1 gene

Question 20

What is the most likely diagnosis for pt presenting with irritability, febrile, anorexia, elevated alkaline phosphatase, firm/ tender swelling of mandible and multiple other sites (clavicles, ribs, long bones, scapula) with Xray showing cortical thickening and subperiosteal new bone formation?

Answer 20

Infantile Cortical Hyperostosis (Caffey disease)

(mutation in COL1A1 gene)

(resolves by 24 months of age)

Question 21

What is the most likely diagnosis for pt presenting with conduction delay on EKG, ASD or VSD on auscultation or ultrasound, and asymmetric upper limb abnormality (a bifid thumb)?

Answer 21

Holt-Oram syndrome

autosomal dominant due to gene on chromosome 12

Question 22

What is the Ghent criteria?

Answer 22

1. Ectopia lentis
2. Aortic dilation or dissection
3. family history of Marfan

(clinical diagnostic criteria for Marfan syndrome)

Question 23

What is the most likely diagnosis for pt presenting with congenital sensorineural hearing loss, heterochromia (pigment abnormalities of iris), white forelock involving forehead and medial eyebrows, displaced medial canthi, facial asymmetry, hypertrichosis of medial eyebrows, prominent nasal root, and cutaneous depigmentation?

Answer 23

Waardenburg syndrome

due to mutation in PAX3 gene on 2q35

Question 24

What is the most likely cause of isolated premature thelarche in a patient with NF1 and increased linear growth velocity prior to pubertal age?

Answer 24

Optic pathyway glioma

Question 25

What is the most likely diagnosis for pt presenting with delayed gross motor milestones, upward displaced showed and abnormal lateral rotation of scapula as child lifted by arms, hypertrophied calves, clumsiness, broadened stance, and forward thrusting of abdomen?

Answer 25

Duchenne Muscular Dystrophy (dystrophin gene on short arm of X chromosome) (associated with Gower sign) (can die from cardiopulmonary disease including sudden death)

Question 26

What genetic syndrome is associated with an echogenic, well defined intracavitary or intramural cardiac mass?

Answer 26

tuberous Sclerosis | mass called a cardiac rhabdomyoma

Question 27

What is the most likely diagnosis for newborn presenting with transient leukemia (transient myeloproliferative disorder, blasts in peripheral blood, lower than in bone marrow) and vesiculopustular? lesions

Answer 27

Trisomy 21 (Down syndrome) | 10-20 fold risk of AML

Question 28

What is the most likely diagnosis for pt presenting with coloboma of retina, heart defect (VSD, aortic arch, TOF), chonal atresia, small for gestational age/ poor weight gain, deafness and ear abnormalities, and micropenis/ cryptorchidism?

Answer 28

CHARGE syndrome (CDH7 gene) C: coloboma H: heart defect A: atresia of choanae (cyanosis that resolves with crying) R: retarded growth and mental development G: genital abnormalities in males E: Ear abdnormalities

Question 29

What is the most likely diagnosis for pt presenting with tall stature, disproportionate limbs, gynecomastia, scant axillary and pubic hair, and behavioral and learning disabilities?

Answer 29

Klinefelter syndrome (47,XXY) -should be evaluated for testosterone therapy

Question 30

What is the most likely diagnosis for pt presenting with short stature, proximal limb shortening, macrocephaly, frontal bossing and midfacial hypoplasia?

Answer 30

Achondroplasia

Question 31

What is the most likely diagnosis in pt presenting with headache, tinnitus, unsteady gait. hearing loss, facial weakness and acoutsic neuroma?

Answer 31

Neurofibromatosis Type 2 (NF 2)

Question 32

What is the most likely diagnosis for pr presenting with Wilm's tumor, aniridia, developmental delay and genitourinary abnormalities?

Answer 32

WAGR syndrome (due to deletion of 11p13

Question 33

What is the most likely diagnosis for pt presenting with cleft palate, micrognathia, glossoptosis, and obstruction of the posterior pharyngeal space by the tongue?

Answer 33

Pierre Robin sequence

Question 34

What 2 syndromes are associated with Pierre Robin sequence?

Answer 34

1. Stickler syndrome (ophthalmologic, auditory, and articular abnormalities) 2. Chromosome 22q11 deletion syndrome

Question 35

What is the most likely diagnosis for pt presenting with doughy, smooth texture skin, poor wound healing, mitral valve prolapse (midsystolic click with late systolic murmur at apex), and joint hypermobility?

Answer 35

Ehlers-Danlos syndrome | collagen defect

Question 36

What is the most likely diagnosis for pt presenting with bilateral radial aplasia, hypotonia, thrombocytopenia, micrognathia, hypertelorism with broad forehead, low set posteriorly rotated ears and intracranial hemorrhage?

Answer 36

Thrombocytopenia with absent radius | TAR associated with septal defects

Question 37

What is the most likely diagnosis for newborn presenting with small for gestational age, micrognathia, index finger overlaping 3rd digit, 5th diigit overlapoing 4th digit, rockerbottom feet, renal anomalies,and cardiac anomalies (septal defects, PDA)?

Answer 37

Trisomy 18 (Edwards syndrome)

Question 38

What is the most likely diagnosis for pt presenting with unilateral absence/ hypoplasia of medial portion of pectoralis major muscle, ipsilateral hypoplasia/ absence of breast/ nipple/ subcutaneous fate, and shortened ipsilateral upper extremity associated with syndactyly

Answer 38

Poland sequence

Question 39

What is the most likely diagnosis for pt presenting with facial muscle weakness and atrophy, neck muscle weakness and distal extremity muscles weakness with normal proximal muscles and conduction defects that can lead to sudden death?

Answer 39

Myotonic dystrophy | autosomal dominant

Question 40

What is the most likely diagnosis for pt presenting with developmental delay, refractory seizures, unilateral facial vascular birthmark involving the upper face and eyelids, and serpentine like intracranial calcifications on imaging?

Answer 40

Sturge Weber Syndrome | CT: dilation of ipsilateral ventricle, calcification, and cerebral atrophy

Question 41

What is the most likely diagnosis for pt presenting with pulmonic stenosis (systolic ejection click on inspiration, systolic ejection murmur at 2nd left intercostal space), bleeding diatheses (factor 11 deficiency), excessive bruising, recurrent epistaxis, short stature, pectus deformity, webbed neck, lowset ears, hypertelorism, cubitus valgus and lymphedema?

Answer 41

Noonan syndrome | 50% due to PTPN11 gene

Question 42

What does VACTERL stand for?

Answer 42

``` V: vertebral A: anal atresia C: cardiac T: trachea E: esophageal R: renal L: limb ``` (must have at least 3 to qualify)

Question 43

What GI disease has a 5-15 fold increased incidence in children with Down's Syndrome?

Answer 43

Celiac Disease | dx: positive antibodies to tissue transglutaminase

Question 44

What endocrine disorder is generally associated with children with Turner's syndrome and Down Syndrome?

Answer 44

Chronic lymphocytic thyroiditis | can have normal or abnormal TFTs, have diffusely enlarged nodular thyroid

Question 45

What chromosomal abnormality is associated with Neurofibromatosis type 1 (NF 1)?

Answer 45

gene mutation on long arm of chromosome 17 | neurofibromin

Question 46

What is the difference between Duchenne muscular dystrophy and Becker muscular dystrophy?

Answer 46

Becker: retain ability to ambulate after 15 years old Duchenne: more severe

Question 47

What is the most likely diagnosis for newborn presenting with prominent epicanthal folds, flattened and small nose and chin, flattened hands (spade like), bilateral club foot, micrognathia, pulmonary hypoplasia?

Answer 47

Potter's sequence | due to congential renal anomalies that lead to oligohydramnios causing fetal compression

Question 48

What is the mode of inheritance for Neurofibromatosis type 1 (NF 1)?

Answer 48

Autosomal dominant

Question 49

What bony abnormality is associated with Neurofibromatosis type 1 (NF 1)?

Answer 49

Sphenoid dysplasia (thinning/ bowing of the long bone cortex)

Question 50

What is the difference between Noonan syndrom (46 XX karyotype) and Turner syndrome (45X) despite most of their clinical features are the same?

Answer 50

different pattern of congenital heart disease Turner: bicuspid aortic vavle or coarctation of aorta Noonan: tetralogy of fallot, ASD, hypertrophic cardiomyopathy

Question 51

What is the most likely diagnosis for pt presenting with index, middle, ring and 5th digit of hands fused with normal thumb in mitten shape, similar fusion of feet, high arched palate, bicoronal synostosis, and maxillary hypoplasia?

Answer 51

Apert syndrome

Question 52

What disorder is associated with radiographic finding of unilateral anterolateral angulation (bowing) of the tibia progressing to thinning of the cortex and pathologic fracture (known as congenital pseudoarthrosis)?

Answer 52

Neurofibromatosis Type 1 (NF 1)

Question 53

What is the most likely diagnosis of newborn presenting with feeding difficulties, generalized muscle weakness, difficulty sucking and swallowing, and polyhydramnios prenatally?

Answer 53

Myotubular Myopathy (maturational arrest of fetal muscle) (X-linked recessive)

Question 54

what is the most likely diagnosis for patient presenting with branchial cleft fistulas/ cysts, preauricular pits, hearing loss and renal anomalies?

Answer 54

Branchio-oto-renal syndrome

Question 55

What are possible concerning complications associated with pt having a Port-wine stain in the V1 distribution? (2)

Answer 55

1. Glaucoma | 2. CNS leptomeningeal angiomatosis (leads to seizures)

Question 56

What GI manifestation is associated with Trisomy 13 (Patau syndrome) and Trisomy 18 (Edwards syndrome)?

Answer 56

Omphalocele | -herniation of abdominal contents into base of umbilical cord

Question 57

What is the differences between Noonan syndrome and turner's syndrome?

Answer 57

1) Karyotype- Turner's is 45 X, Noonan is 46 XX or XY | 2) heart defect- Turner's aortic, Noonan is pulmonic valve stenosis

Question 58

What is the etiology for neck pain, loss of bowel/ bladder, torticollis and/or gait abnormalities in patients with Trisomy 21?

Answer 58

Alantoaxial instability (excessive mobility of the articulation of atlas (C1) and the axis (C2))

Question 59

What is the most likely diagnosis for a patient with a "cocktail party" personality (very friendly) with no insight into dangers of going off with strangers, elfin like facies (puffy eyelid, full mouth), hypercalcemia, and low IQ?

Answer 59

``` Williams syndrome (microdeletion on 7q11.23) ```

Question 60

What does liver biopsy show in patients with Alagille syndrome?

Answer 60

reduced number of bile ducts

Question 61

What ophthalmologic condition is associated with Down's syndrome?

Answer 61

Brushfield spots | white speckled appearance in of iris due to rings of iris hypoplasia

Question 62

What GI manifestation is 5-15 times more common in patients with Downs syndrome?

Answer 62

Celiac disease

Question 63

What is the most likely diagnosis for an infant less than 24 months who is irritable, often febrile, found to have tender mass at mandible and possible other joints with Xray showing cortical thickening and subperiosteal new bone formation?

Answer 63

Caffey Disease | infantile cortical hyperostosis

Question 64

A patient with a wide carrying angle of the elbow and short stature should make you concerned for ....

Answer 64

Turner Syndrome

Question 65

A patient presenting with unilateral anterolateral angulation (bowing) of the tibia with cortical thinning and fracture is likely to have....

Answer 65

Neurofibromatosis 1 (NF-1) | congenital pseudoarthrosis

Question 66

What are the 3 components of Ghent criteria and what is it used for?

Answer 66

1) Ectopic lentis 2) Aortic dilation or dissection 3) Family history Diagnosis Marfans syndrome

Question 67

Prominent distention of the stomach and proximal duodenum associated with an otherwise gasless abdomen is a radiographic sign for ....

Answer 67

Duodenal atresia

Question 68

What is the cause of precocious puberty in patients with Neurofibromatosis-1 (NF-1)?

Answer 68

Optic pathway glioma

Question 69

What are the most common EKG changes associated with hypocalcemia?

Answer 69

1) Prolonged QTc | 2) prolonged ST interval

Question 70

What is a multilocular cystic mass in the nuchal region extending half the length of a fetus on prenatal ultrasound?

Answer 70

Cystic hygroma | associated with aneuploidy

Question 71

What cardiac abnormality is often associated with Williams syndrome?

Answer 71

Supravalvular aortic stenosis | systolic ejection murmur heard at right intercostal space

Question 72

What renal abnormality is often associated with Williams syndrome?

Answer 72

renal artery stenosis | hypertension results

Question 73

What is an area of the scalp devoid of dermis and epidermis that is characterized as sharp demarcated, ulcerated plaque covered by a tense membrane?

Answer 73

Aplasia cutis congenita | associated with Trisomy 13- Patau syndrome

Question 74

What is the most likely diagnosis for patient with tall stature, lens dislocation, pectus excavatum and learning/ developmental delays?

Answer 74

Homocystinuria

Question 75

What is Crowe sign and what diagnosis is it used for?

Answer 75

axilla or inguinal freckling (hyperpigmented macule measuring 1-4 mm) Neurofibromatosis Type 1 (NF-1)

Question 76

... is characterized by small abdominal cavity and herniation of abdominal contents into the base of the umbilical cord.

Answer 76

Omphalocele | have covered membrane

Question 77

What genetic disorders are associated with Omphalocele? (3)

Answer 77

1) Beckwith Wiedemann syndrome 2) trisomy 13 (Patau) 3) trisomy 18 (Edwards)

Question 78

What is the most common cardiac anomaly associated with Noonan's syndrome?

Answer 78

``` Pulmonic stenosis (systolic ejection click louder in inspiration, systolic ejection murmur heard at 2nd left intercostal space) ```