CONGENITAL MALFORMATIONCONGENITAL MALFORMATION

congenital malformationscongenital malformations

IntroductionIntroductionCongenital anomalies are major causes Congenital anomalies are major causes Of still birth and neonatal deathOf still birth and neonatal death

Major congenital malformations occur in Major congenital malformations occur in approximately 3 to 4 percent of live birthapproximately 3 to 4 percent of live birth

Birth defects can be isolated or present in a Birth defects can be isolated or present in a characteristic combination.characteristic combination.

Most common single defects areMost common single defects are

congenital hip dislocationcongenital hip dislocation

club footclub foot

cleft lipcleft lip

cleft palatecleft palate

cardiac septal defectcardiac septal defect

defect in neural tube closuredefect in neural tube closure

In ancient times, birth defects were believed to be In ancient times, birth defects were believed to be result from the action of supernaturalresult from the action of supernatural

DefinitionDefinitionMalformationsMalformations Malformations are defects of organs or Malformations are defects of organs or

body parts due to an intrinsically abnormal body parts due to an intrinsically abnormal developmental process. developmental process.

structure is not formed, is partially formed, or structure is not formed, is partially formed, or is formed in an abnnormal fashion.is formed in an abnnormal fashion.

Malformations often result from a defect in Malformations often result from a defect in embryonic developmentembryonic development

except-CNS,genitalia.teeth…except-CNS,genitalia.teeth…

Malformations can be classified as major and Malformations can be classified as major and minor.minor.

major malformationmajor malformation are those that have medical and/or social are those that have medical and/or social

implicationsimplications These often require surgical repair. These often require surgical repair.

eg. the neural tube defects such as meningomyeloceleeg. the neural tube defects such as meningomyelocele

or orofacial clefting (cleft lip and palate), are common major or orofacial clefting (cleft lip and palate), are common major malformations malformations

Minor malformationMinor malformation have mostly cosmetic significance. They rarely are have mostly cosmetic significance. They rarely are

medically significant or require surgical intervention.medically significant or require surgical intervention. They represent part of the normal variation in the They represent part of the normal variation in the

general population.general population.

Minor anomalies are commonMinor anomalies are common

Approximately 50 percent of minor Approximately 50 percent of minor anomalies are located in the head and neckanomalies are located in the head and neck

Infants with three or more minor anomalies Infants with three or more minor anomalies

are at increased risk of having a major defect are at increased risk of having a major defect or syndrome.(20%)or syndrome.(20%)

eg. clinodactyly (incurving of the fifth eg. clinodactyly (incurving of the fifth

finger), and single transverse palmar creasesfinger), and single transverse palmar creases

DeformationDeformation are abnormalities of the position of body are abnormalities of the position of body

parts due to mechanical forces that modify a parts due to mechanical forces that modify a normally formed structurenormally formed structure

Intrinsic or extrinsic factorsIntrinsic or extrinsic factors

often can be corrected by management often can be corrected by management

eg. clubfoot, congenital dysplasia of the hip, and eg. clubfoot, congenital dysplasia of the hip, and plagiocephaly (lopsided or flattened skull due to compression).plagiocephaly (lopsided or flattened skull due to compression).

DisruptionDisruption Are defects of organs or body parts that result Are defects of organs or body parts that result

from destruction of or interference by external from destruction of or interference by external factor with normal developmentfactor with normal development

two mechanismtwo mechanism amniotic bandamniotic band Interruption of blood supply Interruption of blood supply

Patterns ofPatterns of DefectsDefects SyndromSyndromee is a pattern of anomalies that occur together and is a pattern of anomalies that occur together and

are pathogenetically related.are pathogenetically related. egeg.Down syndrome.Down syndrome

SequenceSequence is a pattern of anomalies in which a single known is a pattern of anomalies in which a single known

defect in development causes a cascade of subsequent defect in development causes a cascade of subsequent abnormalitiesabnormalities

eeg.g. Potter sequence Potter sequence

Developmental field defectDevelopmental field defect is a pattern of anomalies caused by disturbance of a region of is a pattern of anomalies caused by disturbance of a region of

the embryo that develops in a contiguous physical space.the embryo that develops in a contiguous physical space. eg. Bladder exstrophy and cloacal exstrophyeg. Bladder exstrophy and cloacal exstrophy

AssociationAssociation   is defined as two or more anomalies that are not is defined as two or more anomalies that are not

pathogenetically related and occur together more frequently pathogenetically related and occur together more frequently than expected by chance.than expected by chance.

In general, the etiology of associations is not defined.In general, the etiology of associations is not defined. eg.VATER/VACTERLeg.VATER/VACTERL

ETIOLOGYETIOLOGY Not known — 43.1 percent Not known — 43.1 percent Multifactorial — 22.8 percent Multifactorial — 22.8 percent Familial — 14.4 percent Familial — 14.4 percent Chromosomal — 10.1 percent Chromosomal — 10.1 percent Single gene — 4.1 percentSingle gene — 4.1 percent Teratogen — 4.1 percentTeratogen — 4.1 percent Maternal illnessMaternal illness MMaternal infectionaternal infection DDrugrug Envt agent(physical,chemical)Envt agent(physical,chemical) Uterine factorUterine factor NutritionNutrition

TERATOGENSTERATOGENS is an agent that can cause abnormalities in the form or is an agent that can cause abnormalities in the form or

function of a developing fetus.function of a developing fetus. Approximately 4 to 6 percent of birth defects are Approximately 4 to 6 percent of birth defects are

caused by exposure to teratogens in the envt caused by exposure to teratogens in the envt include maternal illnesses (eg, diabetes mellitus or include maternal illnesses (eg, diabetes mellitus or

PKU), infectious agents (eg, TORCH infections), PKU), infectious agents (eg, TORCH infections), physical agents (eg, radiation or heat exposure), and physical agents (eg, radiation or heat exposure), and drugs (eg, thalidomide, antiepileptic drugs) and drugs (eg, thalidomide, antiepileptic drugs) and chemical agents (eg, mercury).chemical agents (eg, mercury).

Depends on maternal genotype, fetal genotype, the Depends on maternal genotype, fetal genotype, the dose of the agent, route of exposure, timing of dose of the agent, route of exposure, timing of exposure, and concurrent exposures or illnesses exposure, and concurrent exposures or illnesses during gestation.during gestation.

TypesTypes

Chemical Retinoic acid Hydrocephalus, microtia, CNS Chemical Retinoic acid Hydrocephalus, microtia, CNS migrations defects migrations defects Thalidomide Limb reduction defects Thalidomide Limb reduction defects Valproic acid Neural tube defects Valproic acid Neural tube defects Phenytoin Dysmorphic features, nail Phenytoin Dysmorphic features, nail hypoplasia,hypoplasia, heart defects heart defects Lithium Ebstein anomaly Lithium Ebstein anomaly ACE inhibitors Renal and skull defects ACE inhibitors Renal and skull defects Misoprostol Fetal death, vascular disruptions Misoprostol Fetal death, vascular disruptions (eg, terminal transverse limb defects) (eg, terminal transverse limb defects)

DES Cervical cancer in female progeny DES Cervical cancer in female progeny

Physical Ionizing Radiation Fetal death, Physical Ionizing Radiation Fetal death, growth retardation growth retardation Hyperthermia Microcephaly, MR, Hyperthermia Microcephaly, MR,

seizures seizures Biological Cytomegalovirus Microcephaly, MR Biological Cytomegalovirus Microcephaly, MR Toxoplasmosis Microcephaly, MR Toxoplasmosis Microcephaly, MR Rubella Microcephaly, MR Rubella Microcephaly, MR MaternalDiabetes CHD, NTD, sacral MaternalDiabetes CHD, NTD, sacral anomalies, anomalies, Phenylketonuria Microcephaly, CHD, MR Phenylketonuria Microcephaly, CHD, MR

Major malformationsMajor malformations

Head and craniofacial structuresHead and craniofacial structures

SkullSkull Anencephaly Anencephaly Encephalocele (occipital, frontal) Encephalocele (occipital, frontal) Holoprosencephaly Holoprosencephaly Hydrocephaly Hydrocephaly EyesEyes Microphthalmia Microphthalmia Anophthalmia Anophthalmia Colobomas (iris, retina) Colobomas (iris, retina) Ears Ears Severe microtiaSevere microtia

MouthMouth and throat and throat Cleft lip* Cleft lip* Cleft palate* Cleft palate* Severe micrognathia (Robin sequence) Severe micrognathia (Robin sequence) Macro or microglossia Macro or microglossia Neck Neck Cystic hygroma Cystic hygroma ChestChest Pectus excavatum Pectus excavatum Absent or hypoplastic clavicles Absent or hypoplastic clavicles BackBack Meningomyelocele Meningomyelocele Spina bifidaSpina bifida

Abdomen Abdomen Omphalocele Omphalocele Gastrochisis Gastrochisis GenitaliaGenitalia Ambiguous genitalia Ambiguous genitalia Extremities Extremities Arms Arms Absent or limb deficiencies Absent or limb deficiencies Hands and feetHands and feet Polydactyly, complete syndactyly, polysyndactyly Polydactyly, complete syndactyly, polysyndactyly Absent digits Absent digits Ectrodactyly Ectrodactyly

Cardiovascular and great vessels*Cardiovascular and great vessels* Tetralogy of Fallot Tetralogy of Fallot Truncus arteriosus Truncus arteriosus Hypoplastic left heart Hypoplastic left heart Ventricular or atrial septal defect Ventricular or atrial septal defect Transposition of the great vessels Transposition of the great vessels Interrupted aortic arch type B Interrupted aortic arch type B Total anomaly of pulmonary venous return Total anomaly of pulmonary venous return

Hypoplasia or coarctation of the aortaHypoplasia or coarctation of the aorta

Neural tube defects (NTDs)Neural tube defects (NTDs) INCIDENCEINCIDENCE depends upon ethnic, geographic, and nutritional depends upon ethnic, geographic, and nutritional

factors. factors. It usually ranges from one to seven per 1000 live It usually ranges from one to seven per 1000 live

birthsbirths Girls are affected more often than boys. Girls are affected more often than boys. For a woman delivered of a child with For a woman delivered of a child with

myelomeningocele, the risk of recurrence in myelomeningocele, the risk of recurrence in subsequent pregnancies is 2.5 percent (about 20 times subsequent pregnancies is 2.5 percent (about 20 times the rate in the general populatithe rate in the general populati

TYPES OF NTDSTYPES OF NTDS

open NTDopen NTD

closeNTDcloseNTD

spinalNTDspinalNTD

Spina bifida — Spina bifida refers to a cleft in Spina bifida — Spina bifida refers to a cleft in the spinal column.the spinal column. MeningoceleMeningocele meningomyelocele or myelomeningocele meningomyelocele or myelomeningocele

Cranial defectsCranial defects AnencephalyAnencephaly ExencephalyExencephaly EncephaloceleEncephalocele ETIOLOGY AND RISK FACTORSETIOLOGY AND RISK FACTORS Folic acid deficiencyFolic acid deficiency Environmental factorsEnvironmental factors Drugs-valproic acid, carbamazepine,Drugs-valproic acid, carbamazepine, folic acid antagonistsfolic acid antagonists DMDM Genetic factorsGenetic factors

ScreeningScreening maternal AFPmaternal AFP DiagnosisDiagnosis u/su/s amniotic AFPamniotic AFPManagement principleManagement principle counselingcounseling abcabc surgerysurgery

orofacial cleftsorofacial clefts Include: Include: 1, Unilateral cleft lip 1, Unilateral cleft lip 2,Unilateral cleft lip and palate 2,Unilateral cleft lip and palate 3,Bilateral cleft lip and palate 3,Bilateral cleft lip and palate 4,Isolated cleft palate4,Isolated cleft palate PrevalencePrevalence cleft lip with cleft palate 50%cleft lip with cleft palate 50% cleft lip 25%cleft lip 25% cleft palate 25%cleft palate 25%• CL/P is more common than CP and varies by ethnicityCL/P is more common than CP and varies by ethnicity

• CL/P high in Native Americans and Asians (1/500 CL/P high in Native Americans and Asians (1/500 newborns), low in American blacks (1/2000 newborns), low in American blacks (1/2000 newborns), and at an intermediate level in Caucasians newborns), and at an intermediate level in Caucasians (1/1000 newborns).(1/1000 newborns).

• isolated CP occurs in only 1/2500 newborns and isolated CP occurs in only 1/2500 newborns and does not display variation by ethnicity.does not display variation by ethnicity.

• 85 percent of bilateral cleft lips and 70 percent of 85 percent of bilateral cleft lips and 70 percent of unilateral cleft lip are associated with cleft palate unilateral cleft lip are associated with cleft palate

EtiolgyEtiolgy genetic defectsgenetic defects Environmental agentsEnvironmental agents

Medications Medications 

Cigarette smokingCigarette smoking

Alcohol Alcohol 

Folate deficiency  Folate deficiency 

Management principleManagement principle

feeding mgtfeeding mgt

surgical repairsurgical repair

speech therapyspeech therapy

orthodontic therapyorthodontic therapy

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