Skeletal Dysplasias Flashcards
Achondroplasia (Tyrion) Gene MOI
Gene: FGFR3
Results from a point mutation
MOI: AD
80% de movo
Increased risk with APA
Clinical features Achondroplasia
Macrocephaly with frontal bossing
Midface retrusion and depressed nasal bridge
Bowlegs
Trident hands
Excessive forward curvature of the spine in the upper back
Hypochondroplasia gene, MOI
GENE: FGFR3; (AD); majority of cases are de nov
Features of hypochondroplasia
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
Cleidocranial dysplasia (Stranger things)
gene, moi
RUNX2, AD
Classic triad for Cleidocranial dysplasia (Stranger things)
Delayed closure of the cranial sutures
Hypoplastic or aplastic clavicles
Dental abnormalities
Diastrophic dysplasia (Little people big world) Gene, moi
SLC26A2, AR
features for Diastrophic dysplasia (Little people big world)
Normal sized head
Slight trunk shortening
Hitchhiker thumb
Fusion of the joints of the fingers or toes
Small chest
CP cystic ear swelling
Hereditary multiple osteochondromas syndrome
Multiple osteochondromas (bony growths)
Gene: EXT1 OR EXT2
MOI: AD
10% de novo
Spondyloepiphyseal dysplasia congenita (SEDC) (harry potter) features
Barrel chest
Hearing loss
Myopia
Delayed ossification of the vertebrae and pubic bones
gene for Spondyloepiphyseal dysplasia congenita (SEDC)
COL2A1, (AD)
most common genes in OI
COL1A1 or COL1A2
OI type 1 Classic non deforming
Blue sclerra
Possible femoral bowing at birth
Joint hypermobility
Progressive hearing loss
OI type 2 Perinatally lethal
Evident at birth
Dark blue sclerra
Connective tissue is extremely fragile
Large, soft skull
OI type 3 Progressively deforming
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
OI type 4 Common variable
Most variable form of OI
Mild to moderately severe
Mild short stature
Normal to gray sclera
genes for craniosynostosis syndromes
FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1
Apert
Gene: FGFR2
MOI: AD
Clinical
Craniosynostosis
Flat forehead
Retracted midface, airway obstruction
Hypertelorism
Learning disabilities
Pfeiffer syndrome
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
Crouzon syndrome
FGFR2, FGFR3
MOI: AD
Clinical
Midface hypoplasia
Prominent nasal bridge
proptosis , strabismus
Underdeveloped upper jaw, overcrowding teeth
Hearing loss
Antley- Bixler features
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
flucanozole can cause similar features to
antley bixler
Saethre- Chotzen
Gene: TWIST1
MOI: AD
Clinical
Underdeveloped eye sockets, cheekbones and lower jaw
Low set hairline
Drooping upper eye lid
⅔ syndactyly
Short stature, scoliosis
Craniofrontonasal
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
Beare-Stevenson cutis gyrata
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
Jackson-Weiss
Gene: FGFR2
MOI: AD
Conductive hearing loss
⅔ toe syndactyly
Multisuture craniosynotosis
Meunke syndrome
Gene: FGFR3
MOI: AD
Features
Abnormally shaped head
Wide set eyes
Flattened cheekbones
Macrocephaly
Some hearing loss
Conductive hearing loss is more common that sensorineural for all FGFR craniosynostosis syndromes except
Muenke
Antley Bixler genes
FGFR2 (AD), POR (AR)
