Dysmorphology Flashcards
measurements
- ht, wt, HC
- arm length, upper body:lower body
- ears, eyes
- chest circumference and inter nipple distance
- palm, finger, foot length
minor malformations
- head/cranial shape and dysmorphic features
- mouth, teeth, palatal shape
- extremity (especially finger and toe) formation
- neck and chest shape
- genitalia malformations
- skin pigmentation, texture changes
- can be seen in general population and do not cause medical problems, but constellation can help us form differential
dysmorphology
refers to visual differences in structural changes in size, shape or placement
malformation
a structural difference that arises from a primary, programmed localized error in morphogenesis
-ex: CHD, polydactyly, cleft in van der Woude
deformation
alteration in shape or structure of a body part that initially differentiated normally; could form normally, but was not able to
-ex: Potter sequence, amniotic bands, twin constraint, Pierre-Robin
disruption
structural defect that results from destruction of a body part that differentiated normally
-ex: amniotic bands
dysplasia
abnormal organizations of cells into tissue as a consequence of a generalized defect in differentiation or growth
-ex: achondroplasia-signaling is off
pes equinovarus
in-turned clubbed feet
pes equinovalgus
out-turned clubbed feet
club feet occurrence
- more common in neurological conditions where innervation fails
- kids born in breach presentation
syndrome
- constellation of findings repeatedly observed in unrelated individuals
- all findings have one underlying cause
dolichocephaly
- thin, narrow head
- normal width
- scaphocephaly is a subtype
sloping forehead with microcephaly
more concerning for underlying brain development
brachycephaly
flattened appearance of head
- common in DS
- plagiocephaly falls into this but is usually due to external factors
epicanthal folds
covering of inner canthi of eyes
-seen in DS, among many other syndromes
inverted epicanthus
inner canthus looks more visible, appears to come from bottom of eye
palpebral fissures
- can be up slanting or down slanting
- in dysmorphology refers to a difference in the expected distance between open eyelids
hypotelorism
shortened inter pupillary distance
hypertelorism
lengthened inter-pupillary distance
telecanthus
lateral displacement of inner canthi; like pseudohypertelorism
tented mouth
often seen with hypotonia
cupid’s bow philtrum
prominence at top of vermillion border
nuchal fold persistence
- excess skin in back of neck
- common in DS, Turner
lower limb edema
- swelling of ankles, feet, legs
- common in Turner
inter nipple distance
measured as a ratio to chest circumference
post-axial
ulnar side
pre-axial
radial side
fisting
associated with Tri13 and Tri18
polydactyly
extra digits
single digital flexion crease
most people have two of these
-
clinodactyly
inturning, usually refers to fingers
dermatoglyphics
finger pad patterning that can give info about development
- arching can be seen with Tri18
- whorls-rarer and can be seen with SLOS
- looping
Noonan presentation example
- hypertelorism, ptosis, strabismus
- widely spaced nipples
- low-set ears
- short stature
- ID, DD
- ASD
- hypospadius
anopthalmia
no eyes
cryptopthalmia
some presence of eye material with abnormal lid formation
low set ears
fail to bi-sect with the plane of the inner canthus
syndactly
webbing or fusion of digits
-cutaneous-skin only
Frasier syndrome
- AR
- presents with syndactly and an/cryptopthalmia
- can also have glomurosclerosis with delayed kidney failure and sometimes GU anomalies especially if 46, XY
smaller, thicker, protuberant ears
common in 22q11
heterochromatic irides
-differences in iris color
-often hypo pigmentation
+common in Waardenburg
Waardenburg
- caused by mutations of PAX3 (Type 1) and MITF (Type 2)
- eyes: heterochromia, dystopia canthorum (ONLY type 1)
- broad, high nasal root with hypoplastic nares
- hearing loss
- white forelock, premature graying, partial albinism, synophrys
long bone length differentiation
- rhizo-proximal shortening of long bone (humerus, femur)
- meso-distal long bone shortening (radius, ulnar, tibia, fibula)
- micro-shortening of all long bones
metatropic dysplasia
- most commonly de novo mutations of TRPV4
- features: epi-and metaphyseal flares, dumbbell long bones, “halberd” appearance in pelvic bones
- can change over time, leads to scoliosis, breathing insufficiency in neonates
supernumerary nipples
extra nipples
Pallister-Killian
- mosaic iso12p, very rare
- hypotonia, ID, seizures, motor skill impairment
- umbilical hernia, polydactyly, hearing loss, micromelia (?)
- supernumerary nipples, streaks of skin hyper pigmentation may be seen
- coarse facial features, with a high rounded forehead, a broad nasal bridge with short nose, hypertelorism, low set ears, round cheeks, thin upper lip
- macroglossia with cleft palate
- sparse hair with receded hair line
anterior fontanelle
if not closed by age 2y, it’s concerning
failure of neural tube closure
leads to anencephaly
craniosynostosis
premature closure of skull sutures that can be due to bone pathology (primary) or CNS and other pathology (secondary)
-prevalence of 1 in 2500 births-sagittal and coronal most commonly affected
Kleeblattschaedel
clover leaf skull shape due to craniosynostosis
primary CS
due to a defect in the suture, nearly all are isolated with only 10-20% being syndromic
secondary CS
results as a consequence of another disorder, such as CNS anomalies, metabolic disorders, blood diseases
CS workup
- Xrays; not usually helpful because bones aren’t calcified enough
- 3D CT-most helpful in documentation
- PE +metabolic workup also useful
Crouzon genetics
-AD mutation in FGFR2 or FGFR3
+relationship with APA
-incidence of 1 in 25000-1 in 50000, so 5% CS
Crouzon phenotype
-brachycephaly
-midface hypoplasia with hyperteloric exopthalmos
+also see strabismus
-beaked nose with hypo plastic maxilla giving relative prognathism
-cervical spine anomalies, rhizomelia
Apert genetics
-AD mutation of FGFR2
+APA
-incidence of 1 in 100K-200K, ~1-2% CS
FGFR2 CS
no genotype phenotype prediction for Apert and Crouzon
Apert phenotype
-brachy, oxycephaly
-midface hypoplasia, hyperteloric exophthalmos
+strabismus
-button nose
-hypoplastic maxilla giving relative prognathism
-mitten-type syndactyly
Pfeiffer genetics
-AD mutation of FGFR1 and FGFR2 \+APA \+possible modifier genes -incidence of 1 in 100K, 1-2% CS -3 subtypes
Pfeiffer phenotype
-craniosynostosis, broad angulated thumbs and great toes
+increased risk for MCA and early demise in types 2 and 3
-type 1: mild, looks like Crouzon
-type 2: severe, clover leaf skull
-type 3: type 2 without kleeblattschadel
Muenke syndrome
- AD mutation of FGFR3
- incidence of 1 in 30K, 8% CS
- causes coronal synostosis, macrocephaly, hand or feet anomalies and hearing loss
holoprosencephaly and de myer sequence
“face predicts the brain” spectrum
-craniofacial and CNS malformation due to impaired midline cleavage of embryonic forebrain
-possible facial features
+cyclopia-ethmocephaly (extreme hypotelorism with blind proboscis)
+cebocephaly (hypotelorism with single nostril-nose)
+premaxillary genesis leading to median cleft of lip and/or palate with hypotelorism
+single central incisor
-brain spectrum
+alobar, semi-lobar, lobar
+pituitary dysfunction with hypopituitarism-least severe brain issues and central incisor
cleidocranial dysplasia
- incidence on 1 in 200K (very rare)
- AD haploinsufficiency of CBFA1 or RUNX2
- causes hypertelorism, midface hypoplasia
- failure of anterior fontanelle closure, hypo/aplasia of clavicles and other skeletal anomalies, short stature
- supernumerary teeth and dental anomalies
- recurrent otitis media, sometimes hearing loss
scalp defect of occiput
pathognomonic for Tri13 and women treated with methimazole (hyperthyroidism)
cleft defect management
-rule out syndromes (glossoptosis, lip pits in case of other management needs)
-cosmetic lip repair in newborn
+rule of 10: lbs, weeks, hematocrit
-special feeding techniques for palatal defect
-ST at 6mo+pre surgical orthodontia if needed
-then surgical palate repair at 10-15mo and hearing assessment
-orthodontia between 1-7y
Pierre Robin Malformation sequence
-pattern of micrognathia, glossoptosis and a U-shaped cleft due to “imprint of tongue”
-can be isolated or part of a syndrome
-most concerning issue, especially in infants is obstructive apnea that can cause ischemic encephalopathy
+management is a medical emergency
cleft lip and palate
-occurs in about 600 newborns
+half of cases have both defect, lip alone is less likely
+more likely to be left sided and isolated
-more common in AA and caucasian pops, less likely in Asians and Native Americans
-if isolated RR is 2-4%
Van der Woude
-AD mutation of IRF6
-can include CL+or-CP
+also see pathognomonic lip pits (88%), adhesion between gums and teeth, hypodontia, ankyloglossia
-CHD can occur
hemifacial microsomia
-unilateral malformation sequence that affects eye, ear, maxilla and mandible
+if bilateral looks like Treacher-Collins without coloboma
+causes facial nerve palsy, mandibular hypoplasia, clefting, ear anomalies, hearing loss and pre auricular pits or tags
+can additionally see vertebral and radial ray, cardiac, and renal anomalies
-incidence of 1 in 5K-1 in 27K with males and right side more likely to be affected
Goldenhar syndrome
form of hemifacial microsomia that also effects epibulbar dermoid
thanatophoric dysplasia
-AD mutations of FGFR3, typically lethal in infancy or prenatally
-tend to have very short limbs with skin folds, enlarged head with prominent eyes and hypertelorism
-narrow chest and short ribs tend to lead to respiratory insufficiency
-Type I distinguishing features
+curved thigh bones and platyspondyly (flattened spinal vertebrae)
-Type II distinguishing features:
+cloverleaf skull
achondroplasia
-AD mutations of FGFR3
+association with APA
-short stature with rhizomelic limb shortening and bowed legs
-trident hand defect
-frontal bossing with midface hypoplasia and macrocephaly
-main concerns in childhood are for spinal cord compression (stenosis at the foramen magnum) and obstructive sleep apnea
diastrophic dysplasia
-AR mutations of SLC26A2
-limb shortening and joint contractions, thumb anomalies and ulnar deviation of fingers (hitchhiker thumbs), club foot
-cleft palate, cystic ear swelling (cauliflower ear)
+even with surgeries some anomalies recur
-low muscle tone and advanced bone age
hypochondroplasia
- AD mutations of FGFR3
- short stature with a stocky build
- rhizo- or mesomelia, brachydactly, limited elbow extension
- mild joint laxity and adult onset osteoarthritis
- macrocephaly with mild to moderate ID/LD
- scoliosis, lumbar lordosis
- genu varum-inward leg bowing
pseudoachondroplasia
-AD COMP mutations
+protein involved in cartilage development and conversion to bone
-short stature noticed over time
+proportionate with shortened arms and legs
+usually first picked up due to waddling gain
-joint pain with progression to osteoarthritis and hyper mobility
-“unaffected” head and face
-dysplastic femoral heads with knock-knees and “sway-back”
lethality in skeletal dysplasias
- femur length ratio <0.16
- chest to abdominal circumference ratio is <0.7
- heart to chest circumference is >50%
Ellis van Creveld
-AR mutations of “” and ““2 gene
+founder mutations in Old order amish and aboriginal populations
-disproportionate short-limb dwarfism
-post axial polydactyly (mainly of hands)
-ectodermal dysplasia
-small chest with shortened ribs
-characteristic AV canal and venous anomalies, including common atrium
OI
- 4 types (1 least severe, 2 most)
- most commonly mutations of COL1a1, COL1a2
- brittle bones with frequent fractures and loose joints
- short stature
- fragility of skin and blood vessels
- brittle, fragile teeth
- wormian bones, or extra bony islands in the skull causing soft cranial vault
- blue sclera
