AnApproachtoDysmorphic

Child

Dr.SidKaithakkodenMD
MBBS,DCH,DNB,MD,MRCPCH,FCPS
alavisaid@aol.com

CongenitalAnomalies
2025%ofperinataldeathsaredueto
lethalbirthdefects
10%ofdeathsininfantsweighing5001500
gm
50%ofdeathsininfants>1500gm

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BirthDefects

EstimatedIncidence

Structural/Metabolic
Heartandcirculation
Musclesandskeleton
Clubfoot
Cleftlip/palate

Genitalandurinarytract
Nervoussystemandeye
Anencephaly
Spinabifida
Chromosomalsyndromes

Downsyndrome(Trisomy21)
Respiratorytract
Metabolicdisorders
PKU
CongenitalInfections
Congenitalsyphilis
CongenitalHIVinfection
Congenitalrubellasyndrome
Other
Rhdisease
07/23/16 Fetalalcoholsyndrome

1in115births
1in130births
1in735births
1in930births
1in135births
1in235births
1in8,000births
1in2,000births
1in600births
1in900births
1in900births
1in3,500births
1in12,000births
1in2,000births
1in2,700births
1in100,000births

Sid

1in1,400births
1in1,000births

MarchofDimes,2000.

CausesofBirthDefects

Multifactorial:2030%
Singlegenedisorders:1020%
Chromosomal:15%
Infection:2.5%
Maternaldiabetes:1.5%
Maternalmedications:12%
Restunknown

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EmpiricRecurrenceRisksforforBirthDefects
Condition

AffectedRelatives(s)
None
0.1
0.04
0.1
0.3

1sib/parent
4
27
3

45
34
2

Cleftlip/palate
Cleftpalateonly
NTD

CHD(any)
VSD
Hypoplasticleftheart

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2sibs/sib&parent
1011
15
8
1011
10
6

 Dysmorpholgy:studyofabnormalforms
Dysmorphic:abnormalappearing
Congenital:atbirth
Anomaly:abnormality
Justbecauseitscongenitalitdoesntmeanits
genetic
Onegoalofthedysmorphologistishelpdetermine
theetiologyofcongenitalanomalies
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Whoneedsadysmorphologyevaluation?
Ahistoryofintrauterinegrowthretardationorfailuretothrive
Abnormalgrowth(short,excessive)
Abnormalorunusualfacialfeatures
Abnormalbodyandlimbproportionsorasymmetry
Majorand/orminorcongenitalanomalies
Microcephaly,macrocephalyorcraniosynostosis
Ambiguousorabnormalgenitalia,earlyorlateonsetofpuberty
Psychomotordelayormentalretardation
Hypotonia,hypertonia
Arelativewithproblemssimilartothoseofpatient
Metabolicproblems
Bleedingtendency
Blindnessordeafness
Asignificantregressionindevelopmentalprogress
Anunusualbodyodor
Excessiveunexplainedvomiting
Unusualbehaviors,especiallywhenassociatedwithminormalformations
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PurposesofaMedicalGeneticsEvaluation:
NewPatients:
Establishorconfirmaspecificdiagnosis
Enableaccurate,individualizedcounseling
Determinepreciserecurrencerisks
Obtainnecessarydiagnostictests
Providespecificeducationandsupport
Initiateappropriatereferrals
Planforfocusedmedicalmanagementandfollowup
EstablishedPatients(followupcare):
Assessnewmedicalproblemsandrelatedconcerns
Determinecompliancewithrecommendedmanagement
Keeppatientsinformedaboutnewdiagnosticand
managementstrategies
Provideongoingageappropriateeducation/support
Helpcoordinatenecessaryreferralsandevaluations
Evaluateotheratriskfamilymembers
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ApproachtoBirthDefects&
CongenitalAnomalies
Recognizeassociatedabnormalitiesandmedicalproblems
Makeanaccuratediagnosis
Giveanaccurate,realisticprognosisandnaturalhistoryof
thedisordertothefamily
Discussoptionsandalternativesformanagement
Deliverappropriatemedicalcareand/ortreatment
Preventsubsequentrelatedcomplications
Optimizequalityoflife
Determineandproviderecurrencerisks
Offergeneticandpsychosocialcounseling
Provideanticipatoryguidanceandeducation
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1. Wherearetheproblems?
2. Whataretheproblems?
3. Whatisthediagnosis?
4. Whatareassociatedproblems?
5. Whencouldtheyhavehappened?
6. Howdidtheyarise?
7. Whydidtheyoccur?
8. Whoisatrisk?
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ObservableDifferences
ofHumanPhenotypes
Normalvariations
Minoranomalies
Majoranomalies
Anomaliesandnormalvariantscanserveas
indicatorsofalteredmorphogenesisand
cluestopatternsofmalformation
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ARangeofPhenotypic
VariationisNormal
Normalspectrumofhumanvariation
ofmorphologicalfeatureswith
absolutelynomedicalsignificance(eg.
Epicanthalfolds,attachedvs.
unattachedearlobes,
Observedin>4%ofthepopulation

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MinorAnomaly
Minorvariationsofnormalmorphological
featuresoflittleofnoknownmedical,
surgical,orcosmeticsignificance
Observedin<4%ofthepopulation

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Hunter, A. G.W. CMAJ 2002;167:367-372

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Copyright 2002 Canadian Medical Association or its licensors

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MajorAnomaly
Abnormalitythathas
Medical
Surgicalor
Cosmeticsignificance

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Suspectageneticconditionor
syndromewhen...

Multipleanomalies
Morethan3minoranomalies
Morethanonemajoranomaly
Onemajoranomalyandafewminor
anomalies

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VariableExpression
Morphologicalfeaturesmaybeexpressedatdifferent
degreesofseverityinindividualsresultingindifferent
levelsofdysfunctionandproblemsforindividualshaving
thesameabnormality,evenwhenduetothesame
etiology
Eachindividualwithaparticularsyndrome,sequence,or
associationwillnothaveeveryknownfeatureofthat
disorder,orallthesamefeaturesasoneanother,evenifin
thesamefamily
Thedegreeofvariableexpressionmaycorrelatewiththe
degreeofpleiotropyinsinglegenedisorders
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IncompletePenetrance
Anallornonephenomenareferringtothe
presenceorabsenceofobservable
phenotypicexpressionoffeaturesofa
dominantdiseaseinanindividualknownto
haveamutantallele
SomeindividualswithTuberousSclerosis
appeartohaveincompletepenetrance

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SexInfluencedorLimited
Expression

Somecongenitalanomaliesand/orgenetic
syndromesduetoautosomaldefectsare
moreeasilyrecognized,oronlyrecognized,
inindividualsofaparticulargender
Sexinfluenced:Genitalhypoplasia,hypospadias,
virulizationwithhypertrophyoftheclitoris
Sexlimited:Hereditaryprostatecancer

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TypesofMorphologic
Abnormalities

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Malformation
Deformation
Disruption
Dysplasia

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Malformation
Defectofmorphogenesisinanorganorstructure
duetoanintrinsicallyabnormalproblemwith
formation,growth,ordifferentiationofanorgan
orstructure
hypoplasiaofanorganorstructure(microtia),
incompleteclosure(NTDs,cleftpalate),incomplete
separation(syndactaly)

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Timing
is
everything!

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Malformationsarenotspecific
Thesamemorphologicaldefect,orevena
similarpatternofabnormalities,mayoccur
as:
Anisolatedanomalyinanotherwisenormalindividual
Afeatureinasyndrome,sequence,orassociation
Afeatureofachromosomedisorder,asinglegene
defect,multifactorialdisorder,orsecondarytoa
teratogeniceffect
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Deformation
Abnormalformorpositionofabodyorregionof
thebodycausedbyextrinsicnondisruptive
mechanicalforcesonanormallydeveloping
structure(fetalconstraint)
clubfoot,congenitalhipdislocation,craniofacial
asymmetry,overfoldedear..

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Disruption
Defectofmorphogenesisresultingfroma
destructivebreakdownof,orinterferencewith,a
normallydevelopingstructureresultingindeathof
cellsortissuedestruction.Maybesecondaryto
mechanicalforces,infections,orevenvascular
events.
Lossofdigitduetoamnioticbands,lackofnormal
limbdevelopmentduetointrauterinevascularaccident

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Dysplasia
Errorofmorphogenesisduetotheabnormal
cellularorganizationoffunctionina
specifictypeoftissuemostoftendueto
singlegenedefects
Achrondroplasia,ectodermaldysplasia,
osteogenesisimperfecta,

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RecognizablePatternsof
Anomalies
Syndromes
Associations
Sequencesorfielddefects

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Syndrome
Multipleanomaliesinoneormoretissuesor
structuresthoughttobepathologicallyrelateddue
toaspecificetiologicmechanism(chromosome
disorder,singlegenedefect,environmentalagent,
orunknownfactor),notduetoarelatedsequence
ofdefectsorfielddefect.
Downsyndrome,Williamssyndrome,FAS,Turner
syndrome,Gorlinsyndrome.

FromGreekmeaningrunningtogether
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Geneticheterogeneity
Evenwhenphenotypicallysimilardisordershave
cleargeneticetiologies,locusheterogeneity,and
sometimesevenallelicheterogeneity,may
complicatelaboratorytestingandinfluence
diagnosis,counseling,management,andprognosis
Locusheterogeneity:TuberousSclerosis,PKD
Allelicheterogeneity:Craniosynostosis,CF

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Sequence/FieldDefect
Constellationofdefectsderivedfromacascadeof
effectsrelatedtoasingleknown,orpresumed,
localizedabnormality(malformation,deformation,
disruption)
Pottersequence
Renaldysplasia,pulmonaryhypoplasia,facialdysmorphisms

Mandibularhypoplasia(Robinsequence)
Cleftpalate

Meningomyelocele
Clubfoot,hipdislocation,hydrocephalus

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Association
Nonrandomoccurrenceofacombination
ofseveralanomaliesnotyetidentifiedasa
specificsequenceorsyndromethatoccur
moreoftentogetherthanbychancealone.
VATERandCHARGEassociations

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GeneralCaveatsofDysmorphology
Havingadiagnosis,evenifbad,ismoreusefulfor
familiesthanhavingnodiagnosis
Awrongdiagnosisisworsethannodiagnosis
A diagnosis depends on the clinical recognition of
patterns of abnormalities as supported by
appropriatelaboratoryandimagingtests
Etiologicalheterogeneityandvariableexpressionof
abnormalities often makes the diagnostic
evaluationchallenging
Time and library/database searches can provide
cluestodiagnosis
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Reasonswhydifficultyindiagnosing
Syndromesmaybeencountered

Someareveryraredisordersnotwelldescribed
Problemswithlumpingandsplitting
Variableexpression
Incompletepenetrance
Sexinfluencedorlimitedexpression
Pleiotropy
Etiologicheterogeneity

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ManagementofCongenitalAnomalies
intheFetusorNewborn
Conductcarefulclinicalevaluation
Reviewfamily,prenatalhistory,andperinatalhistory
Obtaindiagnosticstudies
Imagingstudies:Photographs,Xrays
Laboratorystudies:Chromosome,DNA,biochemicalassays

Ifdeceased,requestautopsyandspecificpathologicalanalyses
Provideparentsanopportunitytoseechild
Name,photograph,obtainhair,memorialize,bury...

Providereferralstosocialwork/psychologicalservicesand
supportgroupsasappropriate
Arrangefollowupgeneticcounseling
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TalkingwithFamiliesaboutBirthDefects

Avoiddeliveryroomdiagnosisandcounseling
Explainmedicalconcernsopenlyandhonestly
Humanizeabnormalfindingsandnotenormalfindings
Usediagnostic/medicaltermsonlyasappropriate
Avoidextensivedifferentialdiagnoses
Becarefulaboutprematureprognostication
Watchyourfacialexpressionsandbodylanguage
Listentoconcernsandadheretotheiragenda
Besupportivebutnotunrealisticorenmeshed
Providefrequent,honestupdatesofaccurateinformation
Providepsychosocialsupportservices

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Ambiguous genitalia of a baby girl - the simple virilising form of

congenital adrenal hyperplasia

AmbiguousGenitalia
Differential virilisation of the external genitalia using the staging system of Prader, from normal female
(left) to normal male (right). Sagittal (upper panel) and perineal (lower panel) views shown.

Ogilvy-Stuart, A L et al. Arch Dis Child 2004;89:401-407

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Investigation flow plan for assessment of ambiguous genitalia

Ogilvy-Stuart, A L et al. Arch Dis Child 2004;89:401-407

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Down syndrome

Trisomy21

Brachycephaly
Flat facial profile
Small ears
Folded helix
Conductive hearing loss
Upslanting palpebral fissures
Epicanthal folds
Iris Brushfield spots
Protruding tongue
Congenital heart defect
Atrioventricular canal
Duodenal stenosis/atresia
Imperforate anus
Hirschsprung disease
Atlanto-axial instability
Hypoplastic iliac wings
Shallow acetabulum

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Joint laxity
Short, broad hands
Fifth finger mid-phalanx hypoplasia
Single transverse palmar crease
Excess nuchal skin
Single transverse palmar crease
Mental retardation
Alzheimer disease
Hypotonia, poor Moro reflex
Hypothyroidism
Acute megakaryocytic leukemia
Increased recurrence risk with
parental translocation
Incidence, 1 in 650-1000 live
births
Full trisomy 21, 94%
Mosaic trisomy 21, 2.4%
Translocation 21, 3.3%
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Trisomy18

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Trisomy18

o
o
o

Incidence:1in3000
Girls:Boys3:1
Lowbirthweightinfant
Mentaldeficiency
Lowsetears
Smalljaw(micrognathia)
Clenchedhands
Hypoplastic(underdeveloped)
fingernails
Umbilicalherniaoringuinalhernia
Diastasisrecti
Cryptorchidism

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Crossedlegs(preferredposition)
Congenitalheartdisease
VSD)
ASD
PDACongenitalkidney
abnormalities
Horseshoekidney
Hydronephrosis
Polycystickidney
Colobomaofiris
Microcephaly
Pectuscarinatum
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Trisomy13
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Trisomy13

Incidence 1 in 5000 live births

Mental retardation, severe
Seizures
Small head (microcephaly)
Scalp defects (absent skin)
Small eyes (microphthalmia)
Cleft lip and/or palate
Eyes close set (hypotelorism) -eyes may actually fuse together
into one
Iris defects (coloboma)
low set ears
Simian crease

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Ventricular septal defect (VSD)

Atrial septal defect (ASD)
Patent ductus arteriosus (PDA)
Hernias: umbilical hernia,
inguinal hernia
Undescended testicle
(cryptorchidism)
Hypotonia
Micrognathia
o Skeletal (limb) abnormalities
Extra digits (polydactyly)

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Marfansyndrome
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Marfansyndrome

Autosomal dominant
Disproportionate tall stature, upper
to lower segment ratio less than 0.85
Arm span to height > 1.05
Dolichocephaly
Long, narrow face
Malar hypoplasia
Micrognathia
Retrognathia
Enophthalmos
Ectopia lentis
Myopia
Retinal detachment
Early glaucoma
Early cataracts
Down-slanting palpebral fissures

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High-arched palate
Aortic regurgitation
Mitral regurgitation
Mitral valve prolapse
Aortic root dilatation
APectus excavatum
Pectus carinatum ortic dissection
Scoliosis
Kyphoscoliosis
Thoracic lordosis
Spondylolisthesis
Arachnodactyly
Caused by mutations in the fibrillin1 gene
About 25% of cases due to new
mutations

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CorneliaDeLangeSyndrome

Theincidenceis1caseper10,000
50,000livebirths
Shortstature
Microcephaly(98%)
Shortneck(66%)
Hirsutism(78%)
Cutismarmorataandperioralcyanosis
(56%)
Hypoplasticnipplesandumbilicus
(50%)
Micromelia(93%)
Undescendedtestes(73%)
Confluenteyebrows(synophrys)(99%)
Longcurlyeyelashes(99%)
Lowanterior&posteriorhairline(92%)
Underdevelopedorbitalarches(100%)

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Neat,welldefined,andarched
eyebrows(asthoughtheyhadbeen
penciled)
Longphiltrum
Antevertednares(88%)
Downturnedanglesofthemouth
(94%)
Thinlip(especiallyuppervermillion
border)
Lowsetears
Depressednasalbridge(83%)
Higharchedpalate(86%)andreportsof
cleftpalate
Lateeruptionofwidelyspacedteeth
(86%)
Micrognathia(84%)

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ApertSyndrome
Craniostenosis
Largelateclosing
fontanels
Gapingmidlinedefect
Flattened,often
asymmetricface
Maxillaryhypoplasiawith
retrudedmidface
Cardiovascular(10%)

Syndactyly
Brachydactyly
Congenitalcervicalspinal
fusion(68%),especially
C5C6
Aplasiaorankylosisof
shoulder,elbowandhip
joints
Trachealcartilage
anomalies
Rhizomelia

Atrialseptaldefect
Patentductusarteriosus
Ventricularseptaldefect

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Turner syndrome
(a) Puffy feet, (b) redundant skin at back of neck. (c) Histology of gonads:
ovarian cortical stroma devoid of germ cell elements.

TurnerSyndrome

Shortstature:
Ovarianfailure:
Nails:Manypatientshave
hypoplasticorhyperconvexnails.
Nevi:Excessivenumbersofnevi
Webbedneck:
Lymphedema
Cubitusvalgus(increasedcarrying
angle):Shortfourthmetacarpalor
metatarsal:Althoughthisfindingis
ofminimalclinicalsignificance,it
canbeacluetothepresenceof
Turnersyndrome.
Shieldchest:

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Eye:Ptosis,strabismus,amblyopia,
andcataracts
Gastrointestinalbleeding:
Hipdislocation:
Scoliosis:Thisoccursin10%
Hypertension:
Murmurs:Cardiovascular
malformationsincludecoarctation
oftheaorta,bicuspidaorticvalve,
andaorticdissectioninadulthood
Thyroid:1030%develop
hypothyroidism.
Cutislaxa:

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Noonansyndrome

Autosomal dominant
Short stature
Failure to thrive in infancy
Triangular face with age
Low-set ears
Nerve deafness
Ptosis
Hypertelorism
Down-slanting palpebral fissures
Epicanthal folds
Myopia
Mental retardation (25%)

Malignant schwannoma
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High arched palate

Micrognathia
Dental malocclusion
Low posterior hairline
Webbed neck
Cystic hygroma
Atrial septal defects
Ventricular septal defects
Pulmonic stenosis
Shield chest, Pectus carinatum
superiorly,
Pectus excavatum inferiorly
Caused by mutations in the
protein tyrosine phosphatase,
nonreceptor-type, 11 gene
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CrouzonSyndrome

Craniosynostosis:resultingin
acrocephaly,brachycephaly,
turricephaly,oxycephaly,flat
occiput
Shalloworbits
FaceMidface(maxillary)
hypoplasia
Eyes

Approximately73%ofpatients
havechronictonsillar
herniation.Ofthese,47%have
progressivehydrocephalus.
Syringomyeliamaybepresent
Hydrocephalus(progressivein
30%)

Exophthalmos(proptosis)
secondarytoshalloworbits
resultinginfrequentexposure
conjunctivitisorkeratitis
Ocularhypertelorism
Divergentstrabismus

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Choanalatresiaorstenosis
Mandibularprognathism
Cervicalfusion(18%),C2C3
andC5C6
acanthosisnigricans
Centralnervoussystem

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Aarskogsyndrome

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Foetal Valproate syndrome

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Prader-Willi syndrome
(marked hypotonia)

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Prader-Willi syndrome

Failure to thrive
Central obesity
Dolichocephaly
Narrow bitemporal diameter
Almond-shaped eyes
Strabismus
Upslanting palpebral fissures,
Myopia
Thin upper lip
Small-appearing mouth
Down-turned corners of mouth
Thick, viscous saliva
Early dental caries
Hypoventilation

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Hypogonadotropic hypogonadism
Cryptorchidism
Osteoporosis
Scoliosis, Kyphosis
Small hands
Syndactyly
Small feet :
Frontal hair upsweep
mental retardation Learning
disabilities
Seizures
Global developmental delay
Childhood polyphagia
Microdeletion of 15q11 in 70%
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(A); A) both

chromosomes 15 are inherited from the mother and the PWS region from the
father is missing (present in about 25 percent of patients) (B); and a defect in methylation
inherited from the father (present in less than 5 percent of patients) (C). In this case, the
genes in the PWS critical region on the chromosome 15 inherited from the father are
inactivated, similar to those of the mother

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Angelman syndrome

The 15q11q13 deletion in Prader-Willi or Angelman syndrome patients is

sometimes just visible under the microscope in a standard cytogenetic
preparation. In most cases a molecular test (FISH or PCR) is needed to
make the diagnosis

Rubinstein-Taybi syndrome
a) The typical face, (b) broad thumb, and (c) characteristic appearance of
large toes

Rett syndrome
characteristic hand-wringing.

45,X

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47,XXY

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47,XX,+13

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47,XX,+18

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47,XX,+21

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46,Y,fra(X)(q27.3)

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Thankyou