Genetic syndromes

Question 1

Dysostosis multiplex, flattened midline face, wide nasal bridge, organomegaly, corneal clouding

Answer 1

Hurlur syndrome (Severe Mucopolysaccharidosis type I)

Question 2

Fibrous dysplasia

Answer 2

McCune-Albright Syndrome

Question 3

Capillary malformation (port-wine stain)

Answer 3

Sturge-Weber Syndrome

Question 4

Sturge-Weber Syndrome findings

Answer 4

Seizures, choroidal vascular malformation, cutaneous capillary malformation/port wine stain, glaucoma, imaging = unilateral serpiginous parenchymal calcifications associated with hemispheric atrophy

Question 5

Neurofibromatosis 1 diagnostic criteria

Answer 5

> = 2 of following: axillary freckling; >= 6 large cafe au lait spots; hamartomas in iris (Lisch nodules); >= 1 neurofibroma; osseous lesions (sphenoid dysplasia/long bone abn/pseudoarthrosis); optic glioma; 1st degree relative with NF1

Question 6

Neurofibromatosis 1 imaging findings

Answer 6

Hyperintense areas in basal ganglia and cerebellum (areas of dysmyelination => cognitive, perceptual, executive, and attention deficit)

Question 7

Multiple cortical and periventricular calcific deposits

Answer 7

Tuberous sclerosis

Question 7

Unilateral serpiginous parenchymal calcifications associated with hemispheric atrophy

Answer 7

Sturge-Weber syndrome

Question 8

Obliteration of the cerebral ventricles associated with loss of gray-white matter differentiation

Answer 8

Cerebral edema

Question 9

Beckwith-Wiedemann syndrome

Answer 9

Macrosomia (height and weight), hemihypertrophy, macroglossia, Wilm’s tumor (HTN, mass, and microscopic hematuria), hypoglycemia (Pancreatic beta cell hyperplasia), abdominal wall defects (omphalocele, diastasis recti, umbilical hernia)

Question 10

Kostmann syndrome

Answer 10

Prolonged neutropenia and no bone marrow reserves due to myeloid arrest (insensitive to G-CSF)

Question 11

Smith-Lemli-Opitz syndrome (SLOS)

Answer 11

Path: Deficiency of 7-dehydrocholesterol reductase => increase plasma 7-dehydrocholesterol. Clx: Syndactyly of 2nd and 3rd toes, microcephaly with narrow bifrontal diameter, broad nasal tip with anteverted nares, hypertelorism and ptosis, cleft palate, micrognathia, and low-set ears. Genetics: AR

Question 12

Zellweger syndrome

Answer 12

Path: Disorder of peroxisomes. Clx: Large anterior fontanelle, high forehead, epicathal folds, cataracts, broad nasal bridge, jaundice (hepatic dysfunction), epiphyseal stippling, renal dysfunction. Genetics: AR

Question 13

Menkes disease

Answer 13

Path: Impaired copper uptake (low copper and ceruloplasmin). Clx: Full cheeks with sagging jowls and lips, fragile and hypopigmented hair and eye brows, neurogenic degeneration at 2-3 months of age. Genetics: X-linked

Question 14

Stickler syndrome

Answer 14

Connective tissue d/o. Midfacial hypoplasia, cleft palate, Pierre robin, hearing loss, eye disease (bad myopia, cataract, retinal detachment)

Question 15

Allgrove or triple-A-syndrome

Answer 15

Achalasia, Alacrima (absent/reduced tears), and Adrenocorticotropic hormone-resistant Adrenal insufficiency (Other sxs: autonomic dysfunction, ID, DD, dysarthria, SN neuropathies)

Question 16

Trisomy 18 (Edward’s syndrome)

Answer 16

Overlapping fingers and hypoplastic nails, rocker bottom feet, cardiac/renal defects, central apnea

Question 17

Rett syndrome

Answer 17

Path: X-linked or de novo mutation MECP2 gene; Clx: male die after birth, female have normal perinatal period => language and motor delay with regression, and seizures (~80%), onset around 6-18 months, live to 20s-30s.

Question 18

4 yo girl, webbed neck, hypertelorism, pulmonic ejection click and systolic ejection murmur.

Answer 18

Noonan syndrome. Karyotype 46,XX or 46,XY. Developmental delay, short stature, heart defect (pulmonary valvular stenosis). Similar to Turner except can happen in boys, has pulmonary stenosis as opposed to aortic malformations, and hypertelorism

Question 19

Klippel-Feil syndrome

Answer 19

Clx: Congenital fused cervical vertebrae (short neck, limited ROM, low hairline at back of head), Sprengel deformity (failure of scapula to descend), atlantoaxial instability, hemivertebrae, scoliosis.

Question 20

Williams syndrome

Answer 20

Clx: Extremely friendly with strangers, elfin-like face (strabismus, peg-like teeth, wide set eyes, upturned nose, large philtrum, pointed chin), low IQ, supravalvular aortic stenosis, hypercalcemia

Question 21

McCune-Albright Syndrome

Answer 21

Triad of 1) Polyostotic fibrous dysplasia, 2) Cafe au lait spots, 3) precocious puberty. Gain of function mutation for G-protein receptors of hormones (ACTH, TSH, GnRH)

Question 22

Painless rectal bleeding and hyperpigmented macules on lips

Answer 22

Peutz-Jeghers syndrome - AR disease with colonic hamartomatous polyps, increase risk cancers

Question 23

Nail Patella syndrome

Answer 23

LMX1B gene mutation => Limb and renal effects => hypoplastic nail, patellar dislocations, iliac horns, and proteinura (can get ESRD)

Question 23

Nail Patella syndrome

Answer 23

LMX1B gene mutation => Limb and renal effects => hypoplastic nail, patellar dislocations, iliac horns, and proteinura (can get ESRD)

Question 24

Bloom Syndrome

Answer 24

AR mutation BLM gene (DNA helicase). Clx: photosensitivity, telangiectasia, inc. cancer, low immunoglobulin (inc. infection), bird like faces

Question 25

Patau syndrome (Trisomy 13)

Answer 25

Defect in development of prechordial mesoderm => MIDLINE DEFECTS => defect in midface, eyes, forebrain => omphalocele, rocker bottle feet, polydactyly (as opposed to overlying fingers in Edwards), CHD, and aplasia cutis congenita

Question 26

Turner syndrome associated disorders

Answer 26

Cubitus valgus, extremity edema at birth => hyperconvex fingernails, Cardiac (bicuspid AV, CoA), renal (horseshoe, duct abn), bone (scoliosis, Madelung deformity), metabolic (dyslipid, diabetes), autoimmune (celiac, thyroid)

Question 27

Brushfield spots

Answer 27

Whitish spots in ringlike configuration around periphery of iris, associated with trisomy 21 esp blue eyes

Question 28

Septooptic dysplasia (SOD)

Answer 28

Absense of optic chiasm/nerve, agenesis of septum pellucidum, midfacial anomalies, microphalus/penis

Question 28

Job syndrome

Answer 28

Autosomal dominant hyper-IgE syndrome. Path => defect in Th17 cells => neutrophils fail to get to tissue sites despite chemotactic chemokines => recruit eosinophils instead => secrete IgE (cause eczema). Clx: FATED => Facies coarse, Abscess (staph), Teeth (2 rows of teeth or retain primary teeth), E (high IgE), Derm (eczema).

Question 29

Denys-Drash syndrome

Answer 29

Wilms tumor, nephropathy, ambiguous genitalia

Question 30

Hearing loss, white forelock, premature graying, telecanthus, iris heterochromia, hyper/hypopigmentation

Answer 30

Waardenburg syndrome => telecanthus (widening of medial canthi)

Question 31

Noonan syndrome clx

Answer 31

Bleeding diathesis (F11 deficiency), short stature, congenital heart defect (pulmonary stenosis), pectus excavatum, webbed neck, low set ears, hypertelorism, lymphedema

Question 32

Infant newborn screen +for CF, what next?

Answer 32

Sweat chloride testing

Question 33

PHACES syndrome

Answer 33

Posterior fossa malformation, Hemangioma (large segmental face, unilateral or bilateral), Arterial anomalies (head and necK), Cardiac anomalies (CoA, PDA, VSD, ASD), Eye abnormalities (Horner, cataract, optic atrophy), Sternal clefting

Question 34

Kabuki syndrome

Answer 34

Clx: Arched eyebrows, long eyelashes, long palpebral fissures with lower eyelids turned out, large protruding earlobes, intellectual disability

Question 35

Tuberous Sclerosis

Answer 35

HAMARTOMAS: Hamartomas in CNS and skin, Angiofibromas skin, Mitral regurgitation, Ash-leaf spots (hypomelanotic macules), Rhabdomyoma (cardiac), Tuberous sclerosis, autosomal dOminant, Mental retardation, Angiomyolipoma (renal), Seizures, Shagreen patches (grayish-brown thick leathery area with orange peel texture)

Question 36

Charcot-Marie-Tooth disease

Answer 36

Aka hereditary motor sensory neuropathy => at 1st to 2nd decade, progressive distal weakness, sensory loss, depress/absent tendon reflexes, high-arched feet => muscle atrophy => upper extremities later in disease. Also skeletal and eye abnormalities.

Question 37

Age for thyroid screening in Trisomy 21

Answer 37

Newborn screen => 6 months => 12 months => annually if normal

Question 38

Trisomy 21 and leukemias (most likely at what age?)

Answer 38

AML if < 1 years old; ALL if > 1 years old

Question 39

Most common heart defects in Trisomy 21

Answer 39

AV canal defects, VSD, ASD, ToF

Question 40

Most common GI defects in Trisomy 21

Answer 40

Duodenal atresia, Hirschsprung disease

Question 41

Newborn girl with microcephaly, ocular hypertelorism, prominent glabella, frontal bossing, beaked nose, hypotonia, seizures

Answer 41

Wolf-Hirschhorn syndrome

Question 42

Newborn with profound hypotonia, SGA, feeding problems, FFT, bifrontal narrowing, thin upper lip, almond-shaped eyes, hypogonadism, bilateral cryptorchidism, small penis

Answer 42

Prader-Willi Syndrome (paterally derived deletion of 15q11-13)

Question 43

Newborn with underdeveloped mandibular and zygomatic bones, absent lower lid eye lashes, microtia, stenosis of external ear canal, down-slanting palpebral fissures, coloboma, and conductive hearing loss

Answer 43

Treacher-Collins syndrome (mandibulofacial dysostosis type 1)

Question 44

Short stature <3%ile, short length of proximal extremities (rhizomelic shortening), trident hands, stenosis of foramen magnum, macrocephaly, flat nasal bridge and midface

Answer 44

Achondroplasia

Question 45

Most common cause of death in achondroplastic children <4 years old

Answer 45

Brain stem compression

Question 46

Most common disease with infantile spasm

Answer 46

Tuberous sclerosis

Question 47

Newborn with long eyelashes, hirsutism, low hairline, downward-turned mouth, IUGD, thin upper lip, micromelia, and syndactyly

Answer 47

Cornelia De Lange syndrome Syndactyly also seen in Smith-Lemli-Opitz Syndrome and Apert Syndrome (SLO also has microcephaly with narrow bifrontal diameter, broad nasal tip with anteverted nares, hypertelorism and ptosis, cleft palate, micrognathia, and low-set ears) (Alpert syndrome also has craniosynostosis and broad thumb) Long eyelashes also seen in Kabuki Syndrome => Arched eyebrows, long palpebral fissures with lower eyelids turned out, large protruding earlobes, intellectual disability

Question 48

Infant with macrodactyly (large digits), hemihypertrophy, lipoma, hemangioma, soft-tissue hypertrophy, and accelerated growth

Answer 48

Proteus syndrome vs Beckwith-Wiedemann which also has hemihypertrophy and tissue hypertrophy => also hypoglycemia, omphalocele, Wilms tumor vs Soto syndrome which has large hands and feet instead of digits, LGA, macrocephaly, prominent forehead, hypertelorism, intellectual disability, large hands and feet

Question 49

Newborn with LGA, macrocephaly, prominent forehead, hypertelorism, intellectual disability, large hands and feet

Answer 49

Soto syndrome vs Proteus syndrome => macrodactyly (large digits), hemihypertrophy, lipoma, hemangioma, soft-tissue hypertrophy, and accelerated growth

Question 50

Brachycephaly, frontal bossing, wormian bones, hypoplastic or absent clavicles, delayed eruption of deciduous teeth, and joint laxity

Answer 50

Cleidocranial dysostosis (Cleido = Clavicle)

Question 51

Newborn with craniosynostosis, brachycephaly, strabismus, hypertelorism, maxillary hypoplasia, beaked nose, proptosis, syndactyly, single nail, broad thumb

Answer 51

Apert syndrome

Question 52

Newborn with craniosynostosis, short stature, deviated nasal septum, malocclusion, malposed teeth, and without limb abnormalities

Answer 52

Crouzon syndrome

Question 53

Newborn with craniosynostosis, broad thumb and toes

Answer 53

Pfeiffer syndrome (vs Apert syndrome which also has maxillary hypoplasia, syndactyly, and proptosis)

Question 54

Friedreich ataxia

Answer 54

Path: autosomal recessive trinucleotide repeat of frataxin gene (iron binding protein) => impaired mitochondrial function => degeneration of spinal cord tracts. Clx: Muscle weakness, loss of DTRs, loss of sensation, staggering gait, nystagmus, kyphoscoliosis, pes cavus, diabetes, hypertrophic cardiomyopathy