Classic Syndromes

Question 1

Treacher Collins:

Answer 1

TCOF1 (AD, 60-90%), POLR1D (AD/AR)
downslating palpebral fissures, eyelid coloboma, missing lower eyelashes, microtia, malar & zygomatic arch hypoplasia
conductive HL
No ID!

Question 2

Cornelia de lange syndrome:

Answer 2

NIPBL (AD, 80%), SMC1A (AD, 5%)
synophris, limb hypoplasia (phocomelia), curly eyelashes, hirsutism, downturned corners of mouth
ID, microcephaly, cardio problems

Question 3

Achondroplasia:

Answer 3

AD, FGFR3 G380R
disproportionate short stature, macrocephaly, trident hand, frontal bossing, midface hypoplasia
foramen magnum stenosis- big complication but treatable now

Question 4

Thanatophoric dysplasia;

Answer 4

AD, FGFR3 R248C/K650E
neonatal lethal (think thanos)
type 1: curved femur, flat vertebral bodies
Type 2: cloverleaf skull, straigh femur, tall vertebra
dx: test for this and achondroplasia w/ single base extension PCR

Question 5

Beckwith-wiedemann syndrome:

Answer 5

11p15 imprinting
Loss of methylation on maternal IC2 most common (lost CDKN2A exp)
Paternal UPD 2nd most common
Macroglossia, posterior helical pits (small depressions on back of ear), hemihyperplasia/macrosomia, omphalocele
Cancer risk: wilms tumor, hepatoblastoma, embryonal

Question 6

Heriditary hemmorhagic telangiectasia:

Answer 6

AD ACVRL1 (52%), ENG (44%)
Epistaxis, mucocutaneous telangiectasias, AV malformations & hemmorhage

Question 7

Aarskog syndrome:

Answer 7

XLR, FGD1
Shawl scrotum, cryptorchidism, cervical vertebral abnormalities, hypertelorism
ID (30%)
tx: orchiopexy

Question 8

Antley-Bixler syndrome:

Answer 8

AR, POR
ambiguous genetalia,. craniosynostosis, choanal atresia, hydrocephalus, neonatal fractures, renal malformations
Frontal bossing, midface hypoplasia, small mout, dysplastic ears
maternal virilization during pregnancy w/ affected fetus
mechansim: cytochrom P450 reductase deficiency leads to disorder of steroid and cholesterol synthesis

Question 9

Bardet-Biedl syndrome:

Answer 9

AR
rod-cone dystrophy, obesity, polydactyly, ID, hypogonadotropic gonadism, renal dysfunction
Renal failure=major morbidity/mortality
dx: TVT BBS1 p.M390R (18-30% of BBS), BBS10 C91fs*95 (10%)

Question 10

Branchio-oto-renal syndrome:

Answer 10

AD, EYA1 (40%), SIX1, SIX5
ear malformations w/ conductive or SNHL, renal malformations, branchial fistulae
branchial fistula= opening on side of neck

Question 11

CHARGE Syndrome

Answer 11

: AD, CHD7
Coloboma, Heart defect, choanal Atresia, growth Retardation, G/U malformations, Ear anomalies (+/- deafness)
cardio=conotruncal defects, arch abnormalities
Echo is important

Question 12

Coffin-Lowry syndrome:

Answer 12

XD, RPS6KA3
profound ID in males, short & fleshy hands, tapering fingers, short stature, microcephaly,
stimulus induced drop episodes
facial features: prominent forehead, prominent ears, large mouth
normal to profound ID in females

Question 13

Cornelia de Lange syndrome:

Answer 13

AD: NIPBL (80%), SMC3, RAD21 or XLR: SMC1A (5%),HDAC8 (4%0
growth retardation, synophrys, upper limb anomalies (hypoplasic middle phalynx of index finger, limb reduction), ID,
Pulmonary valve stenosis or VSD
Facial feature: microbrachycephaly, low posterior hairline, micrognathia

Question 14

Fryns syndrome:

Answer 14

Fryns syndrome: AR, PIGN
LGA, cleft lip/palate, coarse face, diaphragmatic defect, digital hypoplasia, hypoplastic nails
NDD: ID, agenesis of corpus collosum, optic nervy hypoplasia, dandy walker malformation
most are stillborn or die neonatally

Question 15

Greig Cephalopolysyndactyly:

Answer 15

AD, GLI3
Preaxial polydactyly, macrocephaly, syndactyly
DD, ID, seizures
allelic to Pallister hall (GLI3 LOF)

Question 16

Joubert Syndrome:

Answer 16

AR (33 genes); 1 XL gene (OFD1)
Molar tooth sign, DD/ID, retinopathy, renal disease

Question 17

Kabuki syndrome:

Answer 17

AD, KMT2D, KDM6A
fetal finger pads, ID, joint laxity, high palate, short stature, Cleft lip/palate,
CHD, renal anomalies, HL, blue sclerae,
facial features: elongated palpebral fissures, arched eyebrows, large ears

Question 18

Rubenstein-Taybi:

Answer 18

AD, CREBBP (50-70%), EP300 (10%)
Broad digits, microcephaly, CHD, severe ID, beaked nose, cryptorchidism
tumor risk: meningioma, pilomatrixoma, leukemia

Question 19

Smith Magenis syndrome:

Answer 19

AD, RAI1
Hypotonia, DD/ID, FTT, coarsening face over time
midface retrusion, broad-square face, deep set eyes
dx: 90% is gross dels (see balanced parental translocations)

Question 20

VACTERL;

Answer 20

no known genes
Vertebral anomalies, Anal atresia, Cardiac malformations, TE fistula, Esophogeal atresia, Renal anomalies, Limb anomanlies
need 3 of 7 for diagnosis