Transcript N - East Bay Newborn Specialists

Dysmorphology
CHO NICU Lecture
Prepared by PJ
12-16-11
Syndromes to Know
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Trisomy 21,18, 13
Turner’s and Kleinfelters
diGeorge/VCF
VACTERL
Noonan’s
Williams
Orbital distance
Hypotelorism
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Holoprosencephaly
maternal PKU
trisomy 13
Williams- neurodevelopmental d/o, elfin facies, overly cheerful
Hypertelorism
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Apert
cardio-facio-cutaneous
coffin lowry- craniofacial (head and facial) and skeletal abnormalities, mental retardation, short stature, and hypotonia
deletion 4p, 4q, 9p, 11q, 13q
DiGeorge
escobar syndrome- Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint
contractures, pterygia, and respiratory distress
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noonan syndrome
trisomy 8, 13
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CHARGE association
Palpebral length
Short palpebral fissure
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DiGeorge
Fetal alcohol syndrome
maternal PKU effects
trisomy 18
Williams syndrome
Palpebral slant
Slanted palpebral fissures
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Apert
cardio-facio-cutaneous syndrome
cat-eye syndrome (multiple other anomalies present)
coffin-lowry syndrome
deletion of 5p, 9p, 3q, 10q, 15q
noonan syndrome
trisomy 9 mosaic S
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prader willi
trisomy 13, 18
Epicanthal fold
Epicanthal folds
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Deletion 3p, 4p, 5p, 9p, 11q, 13q, 18p
down sydrome
escobar syndrome
duplication 9p
fetal valproate
fragile x
hurler syndrome
hypomelanosis of Ito- hypopigmented whirls along Blashko’s lines and skeletal anomalies
maternal PKU
noonan syndrome
william syndrome
x-linked alpha thal/MR
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Micrognathia
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Pierre Robin Sequence
Fetal alcohol syndrome
Connective tissue: Marshall, Stickler, Marfan, Ehler
Danlos
Velocardiofacial, DiGeorge’s
Treacher Collins syndrome
Trisomy 13, 18
Turner syndrome
Noonan syndrome
Smith-Lemli-Opitz syndrome (inborn error of
cholesterol metabolism)
Russell-Silver syndrome (also downward turned in
mouth)
Cri du chat syndrome
Pierre-Robin
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Robin sequence — micrognathia + glossoptosis + U-shaped cleft palate
Sequence from hypoplasia of mandible > posterior displacement of tongue, prevenTS
palatal closure
Associated with GERD, conductive hearing loss
Upper airway obstruction in neonatal period
– prone positioning
– gavage feeding
– nasal trumpet can help by bypassing obstruction at base of tongue
– More invasivemeasures (trach, surg) if persistent resp difficulty.
Delay closure of palatal defect to avoid worsening upper airway obstruction
The tongue
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Glossoptosis - downward displacement/retraction of tongue(normal sized tongue)
– Pierre Robin Sequence
– Down Syndrome
Macroglossia: Enlargement of the tongue
– drooling, speech impairment, difficulty eating, stridor, airway obstruction
– Beckwith Wiedemann: macrosomia, macroglossia, and abdominal wall defects
– Hypothyroid
– Mucopolysaccharidoses (progressive)
– Down syndrome (papillary and fissured)
Ankyloglossia
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breastfeeding difficulty
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poor latch
maternal nipple pain
FTT
difficulty with speech
lactation consultant
Frenotomy/Frenuloplasty
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? Timing
indications: Br feeding difficulty, articulation
problems, psychologic, periodontal disease
Cleft lip/cleft palate
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Cleft lip is more common in males, cleft palate in females.
Nonsyndromic cleft lip and/or palate: incidence 1:1000
60% association with other anomalies or a syndrome
Environmental Causes
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Chromosomal Causes
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Trisomies 13 and 18 (CL/CP)
Wolf-Hirschhorn or 4p− syndrome (CL/CP)
Shprintzen or 22q11.2 deletion syndrome (CP)
Single-gene disorders
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Maternal seizures, anticonvulsant usage (CL/CP or CP)
Fetal alcohol syndrome (CP)
Amniotic band syndrome (CL/CP)
Treacher Collins syndrome, AD (CP)
Stickler syndrome, AD (CP—particularly Pierre-Robin)
Smith-Lemli-Opitz, AR (CP)
HIGH ARCHED PALATE: associated with Noonan, Turners, 22q11 syndromes, Marfan’s
Lip-philtrum
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Score smoothness of philtrum and thinness of upper lip independently
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Scores of 4 or 5 are consistent with FAS.
prominent, long filtrum - Williams (distinctive, "elfin”features, low nasal bridge,
cheerful demeanor, strong language skills, DD, cardiac)
Malformations of the External Ear
Size of the auricle
•Microtia (small ear)
•Macrotia (large ear)
•Anotia (absent ear)
Shape of the ear
•Cup-shaped
•Lop-ear
•Dysplastic
•Elfin ear (pointed)
•Lobe malformations
Auricular fistulas
Auricular appendages/tags
External acoustic meatus
•Atresia
•Duplication
•Septation
Position of the ear
•Melotia (ear on cheek- lack aural ascent)
•Low set ears
•Synotia (ears are very close to each other in
the midline)
Normal ear anatomy
>3cm in
full term
neonate
Abnormal Size
Microtia -> Anotia
Grade I: Almost complete development of the external
ear with identifiable structures and a small but present
external ear canal
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Grade II: A partially developed ear (usually the top
portion is underdeveloped) with a closed off or stenotic
external ear canal producing a conductive hearing loss.
Grade III: Absence of the external ear with a small
peanut-like structure; absence of the external ear canal.
Grade IV: Absence of the total ear or anotia.
Hearing eval, ENT referral,
surgery usually at 4-6 yo
•In utero exposures: isoretinoin, thalidomide,
FAS, maternal diabetes, Cell cept
•Goldenhar syndrome: unilateral microtia, small
malformed mandible
•Treacher-Collins syndrome: downward slanting
eyes, small jaw, drooping lower eyelid, malformed or
absent ears
•Trisomy 18
•Trisomy 21
•Rubella and intrauterine infections
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Macrotia (length >97% on curve)
•Marfan syndrome
•Fragile X-syndrome
•Oligohydramnios (Potter syndrome)
•Several syndromes: Cerebro-oculo-facial-skeletal
syndrome, Weaver, Lamotte, Nance-Horan, PallisterKillian, Melnick-Needles, Langer Giedion
Abnormal Shape
Pointed ear
Cup shaped ear
Lop ear
Auricular Cleft
Dysplastic Ear
Can be associated with
chromosomal abnormalities:
diastrophic dysplasia, antley
bixler syndrome, trisomy 1315, ancephaly, Treacher
Collins
Abnormal Position of Ear
Low Set Ears
•Low set ear will fall below line
drawn outer canthus of the eye
straight back to the occiput
•Normal set will cross or touch the
same line
•Noonan syndrome, Pena Shokeir
(Neurogenic arthrogryposis, pulmonary hypoplasia, hypertelorism
, Trisomy 18, Down’s
Syndrome, Turners, DiGeorge,
Edwards Syndrome, Goldenhar
with low-set malformed ears)
Auricular appendage or tag
•May have associated
unilateral hearing loss
•Can be removed in
childhood for cosmetic
purposes
Aural Atresia
•Absent or stenotic ear canal
•Normal middle ears- at risk for AOM
•At risk for middle ear cholesteatoma
•Bilateral atresia requires early intervention
with hearing aids
•Surgery to correct atresia performed toward
first decade of life
Preauricular Pits
•Five times the risk of the general
population for permanent hearing
impairment
•Branchio-oto-renal syndrome (most
common inherited syndrome causing
hearing loss)- audiologic testing
•Does not require surgery unless
repeatedly infected or discharges
squamous material
•Incidence of renal anomalies with
isolated pit does not significantly differ
from that of general population
•Screening for renal anomalies more
important when other anomalies/
dysmorphic features present, family
hx deafness, renal or auricular
malformations, or mom with history of
gestational DM
Association with renal anomalies
•Occur in several congenital syndromes: branchio-oto-renal syndrome, CHARGE,
Townes-Brocks syndrome (Lop ears, imperforate anus, hypoplastic kidney, ventricular septal defect, limb anomalies
with autosomal dominant inheritance), Nager, Miller, IFDM
•External ear anomalies possibly with increased risk
•Kugelman 2002 showed in study- similar prevalence of renal anomalies between babies
with pits/tags and those without
•Recommend renal ultrasound in children with ear anomaly accompanied by one of the
following: other malformation/dysmorphic features, family histor of deafness/ear/kidney
malformation, maternal history of gest DM.
•Controversial whether or not to get RUS on child with isolated pit/cup ear
http://sonoworld.com/fetus/page.aspx?id=205
Hand and Upper Limb Anomalies
• Syndactyly
– 1 in 2,000-3,000
– Simple (soft tissue
only) to Complex
(bone or nail fusion)
– May be associated with
other syndromes, esp
craniofacial
– May be due to
amniotic bands
– 10-40% familial
Hand and Upper Limb Anomalies
• Polydactyly
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1 in 500-1,000
Often familial (30%)
Side varies by race!
May be associated with
other syndromes
• Chondroectodermal
dysplasia
• trisomy 21
• trisomy 13
Hand and Upper Limb Anomalies
• Camptodactyly
– PIP flexion deformity
resulting in permanent
flexion
– Affects up to 1% of the
population to some
degree
– Can worsen with
growth spurts!!!!
– May be associated with
other syndromes, but
uncommon
Hand and Upper Limb Anomalies
• Amniotic band syndrome
– Bands originate from
inner lining of amnion
– Extremities may get
tangled and constricted in
the bands
– May be associated with
amniocentesis, trauma
– Often no identified
inciting event
Hand and Upper Limb Anomalies
• Absent radii
– VACTERL association
– Thrombocytopenia with
Absent Radius Syndrome
(TAR)
– Fanconi Anemia
Hand and Upper Limb Anomalies
• Clinodactyly
– Angulation at an IP
joint
– Runs in families
– Associated with over
60 syndromes!
– 35-80% half of pts
with Trisomy 21 have
clinodactyly
Trisomy 18
Kristin Riley, MS IV
Epidemiology
• Incidence of 0.3 per 100 newborn babies
• 3:1 male to female ratio
Etiology
• Trisomy for all or a large part of the 18th
chromosome
– majority have full trisomy 18
• most die within fetal life
• recurrence rate < 1%
– mosaicism for an additional chromosome 18
– partial trisomy 18
Pre-Natal Screen
• 1st trimester screen:
– low beta-hCG
– low PAPP-A
– increased NT measurement
– ~ 90% of trisomy 18 pregnancies can be identified with
< 1% false positive rate using first trimester screening
• 2nd trimester screen:
– low levels of AFP, uE3, and beta-hCG
Integrated Screen
Additional Analyses
• CVS at 10-12 weeks gestation
• Amniocentesis at 15-20 weeks gestation
Key Features
Clinical Findings
in > 50% of patients
• Pre-Natal:
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Polyhydramnios
Altered gestational timing
Small placenta
Single umbilical artery
• General Exam:
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Feeble fetal activity
Weak cry
Hypoplasia of skeletal muscle
Hypertonicity
Diminished response to sound
Clinical Findings
in > 50% patients
• Craniofacial:
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Prominent occiput
Narrow bifrontal diameter
Low-set auricles
Short palpebral features
Small oral opening
Narrow palatal arch
Micrognathia
Clinical Findings
in > 50% of patients
• Hands:
– Clenched hand, overlapping index finger over third
finger and overlapping fifth finger over fourth
– Absence of distal crease on fifth finger with or without
distal creases on third and fourth fingers
– Hypoplasia of nails especially on fifth finger and toes
– Short hallux
Clinical Findings
in > 50% of patients
• Thorax:
– Short sternum with reduced # of ossification
centers
– Small nipples
• Abdomen:
– Inguinal or abdominal wall hernia
Clinical Findings
in > 50% patients
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Hips: Limited hip abduction
GU: Male cryptochordism
Skin: Mild hirsutism of forehead and back
Cardiac:
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VSD
ASD
Auricular septal defect
PDA
Clinical Findings
in 10-50% of patients
• Craniofacial:
Wide fontanels, microcephaly, hypoplasia of orbital ridges,
inner epicanthal folds, ptosis of eyelid, cornial opacity,
cleft lip or cleft palate
• Hands and feet:
Ulnar deviation of hand, hypoplastic or absent thumb,
simian crease, equinovarus, rocker-bottom feet (prominent
calcaneus), syndactyly of second and third toes
Clinical Findings
in 10-50% of patients
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Thorax: Wide-spaced nipples
Genitalia: Hypoplasia of labia majora with prominent clitoris
Anus: Malposed or funnel-shaped
Cardiac: Bicuspid aortic or pulmonic valves
Lung: Malsegmentation
Diaphragm: Muscle hypoplasia
Abdomen: Meckels diverticulum, heterotopic pancreatic and or
splenic tissue, omphalocele
• Renal: Horsehoe defect, ectopic kidney, hydronephrosis,
polycystic kidney
Clinical Findings
in < 10% of patients
• CNS: facial palsy, paucity of myelination, defect
of corpus collosum, hydrocephalus,
meningomyelocele
• Craniofacial: Wormian cranial bones, shallow
elongated sella turcica, slanted palpebral features,
hypertelorism, cataract, micropthalmos, choanal
atresia
• Hands: Syndactyly of 3rd and 4th fingers,
polydactyly
Clinical Findings
in < 10% of patients
• Genitalia: M: hypospadias; F: bifid uterus or ovarian
hyperplasia
• CV: Anomalous coronary a., transposition, TOF,
coarctation of aorta, dextrocardia, aberrant subclavian a.,
intimal proliferation in arteries
• Abdominal: Pyloric stenosis, extrahepatic biliary atresia,
gallstones, hypoplastic GB
• Renal: Hydronephrosis, polycystic kidney disease, Wilms
tumor
• Endocrine: Thyroid or adrenal hypoplasia
Natural History
in Neonatal Period
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Apneic periods
Poor suck which may necessitate NG tube
50% die within the first week
Median survival is 14.5 days
Only 5-10% survive to the first year of life
– some have verbal communication and interact
socially
Our Patient
• Ex 37 2/7 wk M infant born by C/S after
fetal decels noted on tracing transferred to
CHO from Alta Bates due to esophageal
atresia with likely TEF and probable
Trisomy 18. PN hx also + for IUGR and
polyhydramnios.
Hospital Course
 FEN/GI: UAC; UVC; TEF and suspected esophageal atresia (not commonly
associated with Trisomy 18); NPO; NG
 RESP: CPAP
 CV: Echo: fenestrated ASD vs. PFO, VSD< systemic RV pressure
 ID: Ampicillin and Gentamicin for 48 hours with a negative blood culture
 GU: Undescended testes
 Renal: RUS: Horseshoe kidney with right pelviectasis, soft tissue pelvic
mass present
 HCM: No hep B at birth, received vitamin K and erythromycin eye ointment
 GENETICS: karyotype Trisomy 18, genetics consulted
 Neuro: HUS: agenesis of the corpus callosum and dysplastic frontal lobes
 Phototherapy
Physical Exam
• GENERAL: Desats during exam to mid 80’s. Pink,
appears uncomfortable with furrowed brows.
• HEENT: Low-set ears, micrognathia.
• RESP: Coarse breath sounds, transmitted sounds from
NCPAP bilaterally. Subcostal retractions.
• CV: Harsh II/VI holosystolic murmur.
• ABD: Abdomen soft, non-distended.
• GU: Undescended testes bilaterally.
• EXT: Hands clenched in fists with overlapping fingers.
Arachnodactaly, rocker-bottom feet.
References
• Jones, D. Smith’s Recognizable Patterns of
Human Malformation. Sixth Ed.
• Nelson Textbook of Pediatrics, 19th Ed.
• UptoDate
• NICU Manual, Children’s Hospital Oakland