Genetics Flashcards
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?
Marfan’s syndrome
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?
Brushfield spots
What are the most common GI malformations seen in patients with Down Syndrome? (2)
- Duodenal atresia (dilated loops of bowel with air fluid levels in duodenum, bilious vomiting)
- Hirschsprung disease
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?
Cornelia de Lange syndrome
What musculoskeletal malformation is common in Down Syndrome patients?
Atlantoaxial subluxation
(signs of symptomatic spinal cord compression include neck pain, torticollis, gait abnormalities, loss of bowel/bladder control)
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?
Turner syndrome
older age will have short stature, delayed sexual maturation and amenorrhea
What are the 2 most common congenital heart defects associated with Turner’s syndrome?
- Coarctation of aorta
2. Bicuspid aortic valve
What pulmonary manifestation are patients with Marfan syndrome more likely to develop?
Spontaneous pneumothorax
collection of air between the visceral and parietal pleura leading to lung collapse
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?
Velocardiofacial syndrome
spectrum of Digeorge syndrome due to q11.2 microdeletion
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?
Williams syndrome
dx: deletion of elastingene on 7q11.23
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?
Prader-Willi syndrome
(due to missing paternal 15q11 via microdeletion or methylation)
(history of profound neonatal hypotonia and poor feeding)
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?
Alagille syndrome
(due to gene on chromosome 20)
(can have osteodystrophy, lipid abnormalities, and variceal bleeding)
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?
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)
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?
Trisomy 13 (Patau) syndrome
(due to meiotic nondisjunction)
(mortality rate within 1st month is 80%)
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?
Treacher-Collins syndrome
(mandibulofacial dysostosis)
(due to failure of neural crest cells due to mutation on chromosome 5)
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?
Angelman Syndrome
(due to loss of maternal 15q11)
(associated with seizures)
What are the most common EKG changes associated with DiGeorge syndrome (microdeletion of 22q11.2)?
- Prolonged QTc
- prolonged ST
(due to hypocalcemia)
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?
Tuberous Sclerosis
autosomal dominant, gene degect on 9q (TSC1) or 16q (TSC2)
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?
Fragile X syndrome
due to more than 200 repeats of trinucleotide sequence in FMR1 gene
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?
Infantile Cortical Hyperostosis (Caffey disease)
(mutation in COL1A1 gene)
(resolves by 24 months of age)
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)?
Holt-Oram syndrome
autosomal dominant due to gene on chromosome 12
What is the Ghent criteria?
- Ectopia lentis
- Aortic dilation or dissection
- family history of Marfan
(clinical diagnostic criteria for Marfan syndrome)
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?
Waardenburg syndrome
due to mutation in PAX3 gene on 2q35
What is the most likely cause of isolated premature thelarche in a patient with NF1 and increased linear growth velocity prior to pubertal age?
Optic pathyway glioma
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?
Duchenne Muscular Dystrophy
(dystrophin gene on short arm of X chromosome)
(associated with Gower sign)
(can die from cardiopulmonary disease including sudden death)
What genetic syndrome is associated with an echogenic, well defined intracavitary or intramural cardiac mass?
tuberous Sclerosis
mass called a cardiac rhabdomyoma
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
Trisomy 21 (Down syndrome)
10-20 fold risk of AML
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?
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
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?
Klinefelter syndrome (47,XXY)
-should be evaluated for testosterone therapy
What is the most likely diagnosis for pt presenting with short stature, proximal limb shortening, macrocephaly, frontal bossing and midfacial hypoplasia?
Achondroplasia
What is the most likely diagnosis in pt presenting with headache, tinnitus, unsteady gait. hearing loss, facial weakness and acoutsic neuroma?
Neurofibromatosis Type 2 (NF 2)
What is the most likely diagnosis for pr presenting with Wilm’s tumor, aniridia, developmental delay and genitourinary abnormalities?
WAGR syndrome
(due to deletion of 11p13
What is the most likely diagnosis for pt presenting with cleft palate, micrognathia, glossoptosis, and obstruction of the posterior pharyngeal space by the tongue?
Pierre Robin sequence
What 2 syndromes are associated with Pierre Robin sequence?
- Stickler syndrome (ophthalmologic, auditory, and articular abnormalities)
- Chromosome 22q11 deletion syndrome
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?
Ehlers-Danlos syndrome
collagen defect
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?
Thrombocytopenia with absent radius
TAR associated with septal defects
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)?
Trisomy 18 (Edwards syndrome)
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
Poland sequence
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?
Myotonic dystrophy
autosomal dominant
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?
Sturge Weber Syndrome
CT: dilation of ipsilateral ventricle, calcification, and cerebral atrophy
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?
Noonan syndrome
50% due to PTPN11 gene
What does VACTERL stand for?
V: vertebral A: anal atresia C: cardiac T: trachea E: esophageal R: renal L: limb
(must have at least 3 to qualify)
What GI disease has a 5-15 fold increased incidence in children with Down’s Syndrome?
Celiac Disease
dx: positive antibodies to tissue transglutaminase
What endocrine disorder is generally associated with children with Turner’s syndrome and Down Syndrome?
Chronic lymphocytic thyroiditis
can have normal or abnormal TFTs, have diffusely enlarged nodular thyroid
What chromosomal abnormality is associated with Neurofibromatosis type 1 (NF 1)?
gene mutation on long arm of chromosome 17
neurofibromin
What is the difference between Duchenne muscular dystrophy and Becker muscular dystrophy?
Becker: retain ability to ambulate after 15 years old
Duchenne: more severe
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?
Potter’s sequence
due to congential renal anomalies that lead to oligohydramnios causing fetal compression
What is the mode of inheritance for Neurofibromatosis type 1 (NF 1)?
Autosomal dominant
What bony abnormality is associated with Neurofibromatosis type 1 (NF 1)?
Sphenoid dysplasia (thinning/ bowing of the long bone cortex)
What is the difference between Noonan syndrom (46 XX karyotype) and Turner syndrome (45X) despite most of their clinical features are the same?
different pattern of congenital heart disease
Turner: bicuspid aortic vavle or coarctation of aorta
Noonan: tetralogy of fallot, ASD, hypertrophic cardiomyopathy
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?
Apert syndrome
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)?
Neurofibromatosis Type 1 (NF 1)
What is the most likely diagnosis of newborn presenting with feeding difficulties, generalized muscle weakness, difficulty sucking and swallowing, and polyhydramnios prenatally?
Myotubular Myopathy
(maturational arrest of fetal muscle)
(X-linked recessive)
what is the most likely diagnosis for patient presenting with branchial cleft fistulas/ cysts, preauricular pits, hearing loss and renal anomalies?
Branchio-oto-renal syndrome
What are possible concerning complications associated with pt having a Port-wine stain in the V1 distribution? (2)
- Glaucoma
2. CNS leptomeningeal angiomatosis (leads to seizures)
What GI manifestation is associated with Trisomy 13 (Patau syndrome) and Trisomy 18 (Edwards syndrome)?
Omphalocele
-herniation of abdominal contents into base of umbilical cord
What is the differences between Noonan syndrome and turner’s syndrome?
1) Karyotype- Turner’s is 45 X, Noonan is 46 XX or XY
2) heart defect- Turner’s aortic, Noonan is pulmonic valve stenosis
What is the etiology for neck pain, loss of bowel/ bladder, torticollis and/or gait abnormalities in patients with Trisomy 21?
Alantoaxial instability (excessive mobility of the articulation of atlas (C1) and the axis (C2))
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?
Williams syndrome (microdeletion on 7q11.23)
What does liver biopsy show in patients with Alagille syndrome?
reduced number of bile ducts
What ophthalmologic condition is associated with Down’s syndrome?
Brushfield spots
white speckled appearance in of iris due to rings of iris hypoplasia
What GI manifestation is 5-15 times more common in patients with Downs syndrome?
Celiac disease
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?
Caffey Disease
infantile cortical hyperostosis
A patient with a wide carrying angle of the elbow and short stature should make you concerned for ….
Turner Syndrome
A patient presenting with unilateral anterolateral angulation (bowing) of the tibia with cortical thinning and fracture is likely to have….
Neurofibromatosis 1 (NF-1)
congenital pseudoarthrosis
What are the 3 components of Ghent criteria and what is it used for?
1) Ectopic lentis
2) Aortic dilation or dissection
3) Family history
Diagnosis Marfans syndrome
Prominent distention of the stomach and proximal duodenum associated with an otherwise gasless abdomen is a radiographic sign for ….
Duodenal atresia
What is the cause of precocious puberty in patients with Neurofibromatosis-1 (NF-1)?
Optic pathway glioma
What are the most common EKG changes associated with hypocalcemia?
1) Prolonged QTc
2) prolonged ST interval
What is a multilocular cystic mass in the nuchal region extending half the length of a fetus on prenatal ultrasound?
Cystic hygroma
associated with aneuploidy
What cardiac abnormality is often associated with Williams syndrome?
Supravalvular aortic stenosis
systolic ejection murmur heard at right intercostal space
What renal abnormality is often associated with Williams syndrome?
renal artery stenosis
hypertension results
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?
Aplasia cutis congenita
associated with Trisomy 13- Patau syndrome
What is the most likely diagnosis for patient with tall stature, lens dislocation, pectus excavatum and learning/ developmental delays?
Homocystinuria
What is Crowe sign and what diagnosis is it used for?
axilla or inguinal freckling (hyperpigmented macule measuring 1-4 mm)
Neurofibromatosis Type 1 (NF-1)
… is characterized by small abdominal cavity and herniation of abdominal contents into the base of the umbilical cord.
Omphalocele
have covered membrane
What genetic disorders are associated with Omphalocele? (3)
1) Beckwith Wiedemann syndrome
2) trisomy 13 (Patau)
3) trisomy 18 (Edwards)
What is the most common cardiac anomaly associated with Noonan’s syndrome?
Pulmonic stenosis (systolic ejection click louder in inspiration, systolic ejection murmur heard at 2nd left intercostal space)
