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BasicConceptsin Samia Temtamy* & Mona Aglan** Human & Division National Research Centre, Cairo, Egypt Otli O u Definition of

dysmorphology Definition of terms routinely used in the description of Impactofmalformations Impact The difference between major

& minor anomalies Approachtoadysmorphicindividual: a Suspicion & analysisSystematic physical examination Cfitifdii ti on o f

Definition of terms routinely used in thditifbithdft th e escr on o f r d e f A malformation / anomaly: is a primary defect whe

re thibilttifttll th ere s a b as c a lt era on o f s ure, usua ll occurring before 10 weeks of gestation. Examples:cleftpalate,an

encephaly,agenesisoflimb anencephaly, limb or part of a limb. Cleft lip & palate Absence of digits (ectrodactyly) 4 Malform

ationSyndrome: Apatternoffeatures Malformation often with an underlying cause, that arises from several different errors in mo

rphogenesis. “Syndrome” from the Greek “running together”. Single gene disorders (e.g. Apert syndrome) Chromosomaldisorders(e.g.Downs

yndrome) disorders Microdeletion syndromes (e.g. Prader-Willi syndrome)Polygenic disorders (e.g. club foot) ()( Environmental ca

uses ( Teratogenesis ( e.g. Rubella, congenital viral infection, infant of diabetic mother) 6 Association: Anassociationisagroupofano

malies Association: An a that occur more frequently than would be expected by chance alone but that do not have a predicta

ble pattern or unified etiology (e.g. VATER association). Vertebral anomalies, absence of radius & anal atresiaas a part of VATER VAT

ER (VACTERL)= V: vertebral, A: anal anomalies, C: cardiac, TE: tracheo- esophageal fistula, R: radial, renal anomalies, L: limb anomal

ies Deformation: Distortionbyaphysicalforceofan a otherwise normal structure. This could be due to uterine malformation, twi

ns or oligohydramnios(e.g. contractures oflimbsand talipes deformity of . Talipes deformity Multiple joint contractures (arthro

gryposis Disruption: Destructionofatissuethatwas Disruption: Destruction a previously normal. Examples of disruptive agents

include amniotic bands, local tissue ischemia or hemorrhage. ongenital ring constrictions 10 Abnormal cellular organization within ti

ssue resulting in structural changes. For example within cartilage or bone in skeletal dysplasias(e.g. Trident hands Tidthd T r h Ch

aracteristic features fhdli Radiological findings in achondroplasia: Loss of caudal widening (1), short long bones of lower limbs (2)

11 f ac h on Impactofmalformations Impact About 3% of all children born will have a significant congenitalmalformation congenit

al These congenital malformations are responsible for a ortion of neonatal and infant deaths. gpp They also account for about 30% o

f all admissions to It is important to recognize both major and minor malformations as they may lead to the early detection g enetic

disorder. g 12 Significance of minor anomalies of all newborns anomaly have an associated ma r Occurrence of two

minor anomalies j anomaly 90 haveanassociated major Presence of 3 or moreminor anomaly

anomalies of which are 42% of idiopathic MR anomalies anomalies anomalies External minor anomalies in the and neck region and the A

roach to a d y smor hicindividual I-Suspicion & Analysis pp yp A genetic etiology should be suspected if the child has:Congenital an

omalies (e.g major anomaly �or 2 minor anomalies) anomalies) Growth deficit (e.g. short stature or failure to thrive)Developm

ental delay, mental deficit or developmental Failure to develop secondary sexual characteristics Ambiguousgenitalia Ambiguous Funny

looking kid (FLK) 15 Male patient with similarly affected male siblings or maternal male relatives suggests X-linked disorder. Family

pedigree suggestive of an X-linked disorder 17 History of miscarriages, stillbirths or early neonatal deaths suggests the possibility

of a parental balanced chromosomerearrangement chromosome . Family pedigree with multiple stillbirths and abortions 19 Environment

al hazards for the fetus: Iftit(ibtiit) f ous agen t s ( e.g. v i ruses, b er a, paras it es… Physical agents (e.g. radiation, heat…

.)Drugs & chemicals Mtlft(dibtllithti t f b e t es me llit us, History of growth & Development Piititi P ons Findin s that su gg est

a p ossible underl y in etiolo gy : gggpyggy Short stature (height below -3SD) or tall stature (height above + 3 SD)(SD=standarddev

iation) + 3 SD) A short father & son with p y Short female with Turner syndrome py p py dysplasia Facialfeatures Facial e.g. Sy

nophrys(fused eyebrows) Innercanthaldistance (decreasedinner distanceor g canthal hypertelorism(increased inner canthaldistance) 2

8 E E e.g. corneal opacities, heterochromiaor other eye abnormalities Corneal o p acit Congenital glaucoma 31 E E Abnormal ear positio

n (low-set, posteriorlyrotated…). When drawing an imaginary line between the outer canthusand the occiput, usually 1 / 3 of the ear i

s above this line) Low-set, posteriorlyrotated ear Low-set ears 34 Mouth&lips Mouth & Abnormal lips (thin/full, tented, down turn

ed, cleft), big or small mouth (macrostomiaor microstomia) Thin tented lips Cleft lip Thick patulous lips Lip pits MacrostomiaMicrosto

mia Oral cavity, tongue, palate & mandible Tongue (e.g. macroglossia, bifid tip…) bifid or absent ) () Prognathism, micrognathia(small

mandible), pointed chin Macroglossia (large tongue) with bifid tip Micrognathia Pointed chin 38 Bifid uvula Rdti(b)dft R e d on b d

e f Hemimelia (absent forearm & hand)) Ectrodactyly (absent toes) 41 Apodia (absent foot) Axial hand reduction (split hands) Othlibli

Oth er b anoma li es Rocker bottom feet with sandal gap Clasped thumb (adducted & flexed)Macrodactyly (large digits) Skin Skin e.g.

pigmentation, scales, pterygium, appendages…. Facialhemangioma Hypopigmented area o n e e h oteoeead Areas of hyper & hypopigment

ationof skin 46 Generalized hypopigmentation Café-au-lait spots Hi H a i Abnormal amount of hair (alopecia, hirsutism, hypertrichos

is) Alopecia Hypertrichosis (long eye lashes) Abnormalhairline(lowhairlineorrecedinghairline) Abnormal Abnormal hai

r color (e.g. white forelock, albinism) Receding anterior hair line with hair hypopigmentation Silver colored hair hair as a part of v

itiligo Abnormaljointshapeormobility Abnormal shape Hyper extensibility of wrist joint Hyper extensibility of knee joint 53 A

bdomen Abdomen Abdominal wall defects (omphalocele, gastroschisis) Ubililhi Gthii h G i s Genitalia e.g. ambiguous genitalia Micropeni

s Clitromegaly46,XX DSD 56 II-Confirmation of diagnosis: Iditifhli or c h romosome ana l ys Ambiguous genitalia Developmentaldelaywith

majorand/orminoranomalies Developmental History of more than 2 miscarriagesIndications for metabolic screening: Metabolicd

isordersknowntocause disorders, peroxisomaldisorders and disorders of cholesterol synthesisRadiological examination for bony

changes and neuroimagingof brain structures. Similarly affected family members 57 Summary A congenital anomaly or birth defect is an

abnormality of structureorfunctionthatispresentatbirth Summary structure Birth defects may be mild or serious. les in d

y smor include the pp ypgy and if it is a single system or multi-system defect. Accurateidentificationofasyndromeisanecessary Accura

te a a management for the affected infant as well as genetic counselingfortheparents counseling . UflR AaseJM. Di

agnostic Dysmorphology. Springer, 1990 JonesKLSmith ’ sRecognizablePatternsofHumanMalformations: l R Smiths Expert Consult O

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Genetics) 4 University Press Inc. 2001Hall JG, Froster-IskeniusUG, AllansonJE. Handbook of Normal Measurements. Oxford: Oxf

ord University Press, 1989 TaybiH, LachmanRS. Radiology of syndomes. Metabolic Disorders ed. Mosby, 2006TemtamySA, McKusickVA. (1978)

The Genetics of Hand Malformations. NewYork, Alan R Liss, Inc. 1978GohDLM. Approach to a dysmorphicIndividual. Bulletin 17, MITA (P)