Week 9: CTDs & skeletal dysplasias Flashcards
Tell me about OI
Primary features:
-Blue sclera
-Wormian bones
-Bones: thin, osteopenic
-Enamel cracks away from dentin and short roots
-Fractures and deformities
OI type I:
-Mild bone fragility
-Bimodal fracture curve
-Normal stature
-Blue sclera
-Susceptible to conductive hearing loss
-+/- dentinogenesis imperfecta
OI type II:
-Perinatal death
-Extremely short stature
-Severe bone fragility
OI type III:
-Progressively deforming type
-Severe short stature
-Multiple bone fragility
-Hearing loss
-Dentinogenesis imperfecta
-AD, rare AR
OI type IV:
-Mild to moderate bone fragility
-+/- hearing loss
-Dentinogenesis imperfecta
-NO blue sclera
-AD
Tell me about Crouzon syndrome
-Craniofacial syndrome
-Usually FGFR2, AD
-Airway obstruction: choanal stenosis, tracheal abn, tongue based obstruction
-Normal extremities
-Usually normal intelligence
-25% with vertebral fusion
Tell me about Pfeiffer syndrome
-Multisuture craniosynostosis
-AD: FGFR1 and FGFR2
-Significant overlap with Crouzon
-Midface retrusion
-Hearing loss
-Airway obstruction
-Broad thumbs and great toes
-Normal-severe ID
-Some require surgical intervention
Tell me about Apert syndrome
-Craniosynostosis
-FGFR2, AD
-Majority have turribrachycephaly
-Midface retrusion
-Hearing loss
-Airway obstruction
-“Mitten” syndactyly w or w/o polydactyly
-Variable ID/DD
-GI abn (malrotation, CDH, etc)
Are most causes of craniosynostosis syndromic or nonsyndromic?
Nonsyndromic (65% of cases)
Tell me about Stickler syndrome
-Usually AD: COL2A1, COL11A1, & more
-Depends on causative variant/type of stickler. Some have features without eye findings, some have ONLY eye findings
-High myopia
-Retinal detachment
-Vitreous anomaly
-Deafness
-Cleft palate
-Early onset joint disease
-Important to consider when have pt with high myopia!
Tell me about achondroplasia
-Most common cause of disproportionate short stature
-FGFR3, AD, complete penetrance, 80% de novo
-Homozygous individuals=severe disease
-Rhizomelic shortening
-Macrocephaly
-Characteristic facial features
-Hypotonia
-Intelligence and lifespan near normal
-Sleep apnea
-Middle ear dysfunction
-Kyphosis
-Spinal stenosis
Tell me about hypochondroplasia
-FGFR3, AD, most de novo
-Very similar to achondroplasia but tend to be milder
-ID thought to be higher in hypochondroplasia
-Short stature
-Stocky
-Disproportionate short arms and legs
-Broad, short hands and feet
-Joint laxity
-Macrocephaly
Tell me about Marfan syndrome
-FBN1, AD
-Eyes: ectopia lentis, myopia, increased risk for retinal detachment, elongated globe, flat cornea
-Skeletal: excessive linear growth, extremities disproportionately long for size of trunk, joint laxity, scoliosis, thumb and wrist signs, flat fleet, pectus excavatum or carinatum
-Cardiovascular: dilation of aorta, mitral valve prolapse, tricuspid aortic valve, enlargement of the proximal pulmonary artery
-Craniofacial: long and narrow face with deep set eyes, downslanting palpebral fissures, malar hypoplasia, micrognathia, high arched and narrow palate, dental crowding
-Need a systemic score (list of marfan features) of 7+ to be sus for Marfan
Tell me about Loeys-Dietz
-TGFBR1, TGFBR2
-Cardio: dilation of the aorta (more aggressive than Marfan syndrome), mitral valve prolapse, enlargement of the proximal pulmonary artery, aneurysms, arterial tortuosity most commonly seen of the head and neck vessels, other (PDA, VSD, BAV)
-Musculoskeletal: skeletal overgrowth less pronounced than in Marfan syndrome, pectus excavatum or carinatum, joint hypermobility, spine anomalies, scoliosis, acetabar protrusion, pes planus
-Craniofacial (variable!): hypertelorism, craniosynostosis, bifid uvula, malar flattening, retrognathia
-Cutaneous: velvety, thin, translucent skin, easy bruising, slower scar formation and dystrophic scarring
-Other: retinal detachment rarely reported, myopia less frequent than Marfan, increased risk for food allergies, asthma, eczema, DD in few, spontaneous rupture of spleen and bowl, uterine rupture during pregnancy
What are two cardiovascular features seen in Loeys-Dietz but not in Marfan
-Arterial tortuosity
-Aneurysm of aortic branch arteries
Name some features more unique/common to both LDS and Marfan to differentiate them
Marfan:
-Lens dislocation
-Tall stature more common
-Long limbs more common
LDS:
-Hypertelorism
-Bifid uvula
-Widespread vascular disease and arterial tortuosity
Tell me about vascular EDS
-AD, COL3A1
-Those with null variants have a 15 year delay in onset of complications, imprpved life expectancy, and significantly, improved life expectancy with fewer obstetric and bowel complications, milder disease course
-Vascular rupture or dissection, GI perforation, or organ rupture are the presenting signs in most adults
-Avg age of first major event is ~31 years old
-Cardiovascular: arterial rupture, venous varicosities
-GI: perforation of GI tract, screening colonoscopies may be avoided
-Craniofacial: thin vermillion of lips, micrognathia, narrow nose, prominent eyes
-Other: small joint hypermobility, pneumothorax, hemoptysis, dental complications
Tell me about classic EDS
-Commonly COL5A1 and COL5A2, AD
-Characterized by skin hyperextensibility, poor wound healing, and joint hypermobility
-Joints: hypermobility, instability, dislocations
-Skin: hyperextensibility, abnormal scarring
-Other organs: gums, eyes, heart and other blood vessels
Tell me about hypermobile EDS
-Generalized joint hypermobility, systemic features, strict criteria for hEDS
-Clinical dx!! No genetic testing
-Soft/velvety skin
-Skin hyperextensiblity
-Unexplained striae
-Piezoggenic papules of the heel
-Recurrent hernias
-Atrophic scarring
-Dental crowding
-Wrist sign, thumb sign
-Mitral valve prolapse
-Aortic root dilation
-Progresses through phases: hypermobility ->pain phase -> stiffness phase
-Variability!
