Skeletal Dysplasias

Question 1

Achondroplasia (Tyrion) Gene MOI

Answer 1

Gene: FGFR3
Results from a point mutation
MOI: AD
80% de movo
Increased risk with APA

Question 2

Clinical features Achondroplasia

Answer 2

Macrocephaly with frontal bossing
Midface retrusion and depressed nasal bridge
Bowlegs
Trident hands
Excessive forward curvature of the spine in the upper back

Question 3

Hypochondroplasia gene, MOI

Answer 3

GENE: FGFR3; (AD); majority of cases are de nov

Question 4

Features of hypochondroplasia

Answer 4

Stocky build
Shortening of the proximal or middle segment s of the extremities
broad , short hands and feet with brachydactyly
Macrocephaly with relatively normal facies

Question 5

Cleidocranial dysplasia (Stranger things)
gene, moi

Answer 5

RUNX2, AD

Question 6

Classic triad for Cleidocranial dysplasia (Stranger things)

Answer 6

Delayed closure of the cranial sutures
Hypoplastic or aplastic clavicles
Dental abnormalities

Question 7

Diastrophic dysplasia (Little people big world) Gene, moi

Answer 7

SLC26A2, AR

Question 8

features for Diastrophic dysplasia (Little people big world)

Answer 8

Normal sized head
Slight trunk shortening
Hitchhiker thumb
Fusion of the joints of the fingers or toes
Small chest
CP cystic ear swelling

Question 9

Hereditary multiple osteochondromas syndrome

Answer 9

Multiple osteochondromas (bony growths)
Gene: EXT1 OR EXT2
MOI: AD
10% de novo

Question 10

Spondyloepiphyseal dysplasia congenita (SEDC) (harry potter) features

Answer 10

Barrel chest
Hearing loss
Myopia
Delayed ossification of the vertebrae and pubic bones

Question 11

gene for Spondyloepiphyseal dysplasia congenita (SEDC)

Answer 11

COL2A1, (AD)

Question 12

most common genes in OI

Answer 12

COL1A1 or COL1A2

Question 13

OI type 1 Classic non deforming

Answer 13

Blue sclerra
Possible femoral bowing at birth
Joint hypermobility
Progressive hearing loss

Question 14

OI type 2 Perinatally lethal

Answer 14

Evident at birth
Dark blue sclerra
Connective tissue is extremely fragile
Large, soft skull

Question 15

OI type 3 Progressively deforming

Answer 15

Most do not walk without assistance
Water temp difference at belly button
Extreme growth delay and very short stature
Barrel chest
Hearing loss in teenage years

Question 16

OI type 4 Common variable

Answer 16

Most variable form of OI
Mild to moderately severe
Mild short stature
Normal to gray sclera

Question 17

genes for craniosynostosis syndromes

Answer 17

FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1

Question 18

Apert

Answer 18

Gene: FGFR2
MOI: AD

Clinical
Craniosynostosis
Flat forehead
Retracted midface, airway obstruction
Hypertelorism
Learning disabilities

Question 19

Pfeiffer syndrome

Answer 19

FGFR2, FGFR1
MOI: AD

Clinical
Normal to cloverleaf skull
Midface retrusion
Conductive hearing loss
Thumbs and great toes are broad and medially deviated, variable brachydactyly
Seizures

Question 20

Crouzon syndrome

Answer 20

FGFR2, FGFR3
MOI: AD

Clinical
Midface hypoplasia
Prominent nasal bridge
proptosis , strabismus
Underdeveloped upper jaw, overcrowding teeth
Hearing loss

Question 21

Antley- Bixler features

Answer 21

Clinical
Both coronal sutures fuse before birth, rarely lambdoid and metopic sutures are also fused
Midface hypoplasia
Choanal atresia or stenosis
Multiple join contractures, arachnodactyly

Question 22

flucanozole can cause similar features to

Answer 22

antley bixler

Question 23

Saethre- Chotzen

Answer 23

Gene: TWIST1
MOI: AD
Clinical
Underdeveloped eye sockets, cheekbones and lower jaw
Low set hairline
Drooping upper eye lid
⅔ syndactyly
Short stature, scoliosis

Question 24

Craniofrontonasal

Answer 24

Gene: EFNB1
MOI: X-linked
Primarily early fusion of coronal sutures
Females have frontonasal dysplasia, craniofacial asymmetry, craniosynostosis, bifid nasal tip, grooved nails, wiry hair
Males often have hypertelorism

Question 25

Beare-Stevenson cutis gyrata

Answer 25

Multi Suture craniosynostosis with cloverleaf skull
Moderate to severe midface retrusion, abnormal ears, CP, conductive hearing loss, tongue-based airway obstruction
Intellectual disability
Genitourinary anomalies

Question 26

Jackson-Weiss

Answer 26

Gene: FGFR2
MOI: AD
Conductive hearing loss
⅔ toe syndactyly
Multisuture craniosynotosis

Question 27

Meunke syndrome

Answer 27

Gene: FGFR3
MOI: AD
Features
Abnormally shaped head
Wide set eyes
Flattened cheekbones
Macrocephaly
Some hearing loss

Question 28

Conductive hearing loss is more common that sensorineural for all FGFR craniosynostosis syndromes except

Answer 28

Muenke

Question 29

Antley Bixler genes

Answer 29

FGFR2 (AD), POR (AR)