Slide 1Objectives See course web page for full objectives Read : 280-284, 289-290 (not Bayes theorem section)Slide 3Incidence of Major Birth Defects in InfantsCauses of Birth DefectsSlide 6Slide 7Slide 8Slide 9Purposes of a Clinical Genetics EvaluationsClassification of Observable DifferencesSlide 12A Range of Phenotypic Variation is NormalSlide 14Slide 15Slide 16Minor AnomalySlide 18Slide 19Major AnomalySlide 21Slide 22Slide 23Types of Morphologic AbnormalitiesSlide 25MalformationSlide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Malformations are Not SpecificSlide 35Etiologic HeterogeneityDeformationSlide 38DisruptionSlide 40DysplasiaSlide 42Slide 43Slide 44Recognizable Patterns of AnomaliesConsider a genetic condition or syndrome when...Slide 47SyndromeSlide 49Sequence/Field DefectSlide 51AssociationReasons Why Difficulty in Diagnosing Syndromes may be EncounteredGenetic heterogeneityVariable ExpressionIncomplete PenetranceSlide 57Slide 58Sex-Influenced or Limited ExpressionSlide 60Management of Congenital AnomaliesTalking about Birth DefectsAdam and Eve Romulus Vuia (1922)Cassatt children, Mary CassattAn Approach to Birth Defects: Perspectives in DysmorphologyElizabeth M. Petty, MDAssociate ProfessorMolecular Medicine and [email protected] course web page for full objectives Read : 280-284, 289-290 (not Bayes theorem section)•Understand that birth defects are common and have a major impact on health•Recognize normal variants, major anomalies, and minor anomalies, and know they may serve as clues to diagnoses•Know that four basic different kinds of errors of morphogenesis can occur. Understand what they are and how they might arise.•Know what is meant by syndrome, field defect or sequence, and association• Be familiar with how to sensitively and comprehensively approach birth defects in patients• Every 8 seconds a baby is born; 10,799 babies are born daily• Every 3 minutes a baby is born with a birth defect • 17 babies die due to a birth defect each day• More than 1 in 5 infant deaths are due to birth defectsBirth defects are the leading cause of infant mortality with 20 - 25% of perinatal deaths due to lethal birth defects 10% of deaths in infants weighing 500 - 1500 gm50% of deaths in infants > 1500 gmIn the United States...•* CDC annual estimate of 150,000 babies born with birth defects•Source: National Center for Health Statistics, 1998 final natality and 1998 period linked birth/infant death data. Prepared by March of Dimes Perinatal Data Center, July 2000Incidence of Major Birth Defects in Infants 3%Causes of Birth Defects•Multifactorial: 20-30%•Single gene disorders: 10-20%•Chromosomal: 15%•Infection: 2.5%•Maternal diabetes: 1.5%•Maternal medications: 1-2%•Rest unknownEmpiric Recurrence Risks (%) for Selected Birth DefectsCondition Affected Relatives(s) None 1 sib/parent 2 sibs / sib & parent Cleft lip/palate 0.1 4 10-11Neural Tube Defect 0.1 3 8 Heart Defect 0.3 4-5 10-11 The risk of having any one major birth defect is less than 1% but this risk increases significantly if other relatives have same birth defectDysmorpholgy: study of abnormal formsDysmorphic: abnormal appearingA dysmorphologist helps assess the extent, etiology, recurrence risk and management options of congenital anomalies. Congenital: at birth, eg. born withAnomaly: abnormalityJust because it’s congenital it doesn’t mean it’s genetic.What are the problems?When did they happen?How did they arise?Why did they occur?What is the diagnosis?Who else is at risk?Where can the patient/family get help?Dysmorphology exam helpful when there is:• Abnormal growth and/or proportions • Abnormal or unusual features and birth defects• Abnormal genitalia and/or puberty • Psychomotor delays, speech delays, or mental retardation • Abnormal neuromuscular function• Bleeding tendencies• Blindness or deafness• Metabolic problems (eg. regression in abilities and/or behavior, unusual body odors, excessive unexplained illness)Purposes of a Clinical Genetics Evaluations•Recognize medical problems•Make accurate diagnosis•Provide prognosis and natural history information•Discuss management•Deliver appropriate medical care •Minimize related complications •Optimize quality of life •Determine and provide recurrence risks •Offer genetic and psychosocial counseling•Provide anticipatory guidance and educationClassification of Observable Differences •Major anomalies•Minor anomalies•Normal variations Why? Because anomalies and variants can serve as indicators of altered morphogenesis and clues to patterns of malformationPPHHYYSSIICCAAL L NAME:______________ DATE:____REG #:______________________________DOB: _____ AGE:___________VITAL SIGNSBP: RA ______ LA ______RL ______ LL ______HR: RR ___ LR ___ RDP ___ LDP ___RR: ______ HEIGHT: _____in ______cm ( %)WEIGHT: _____lbs ______kg ( %)HEAD - NECKGeneral description:HEAD CIRCUM.: ______cm ( %)Cranium/Sutures:Hair distribution:Eyes: IC: ______cm ( %)OC: ______cm ( %)IP: ______cm ( %)RPF: ______cm ( %)LPF: ______cm ( %)Ears: shape:placement:R ______cm ( %)L ______cm ( %)Philtrum: ______cm ( %)Lips:Palate and mouthTeeth:Chin:Neck:TRUNK - ABDOMENGeneral description:sternum:spine:Breast: Tanner Stage: ______Heart:Lungs:Chest circumference: ______cmInter nipple distance: ______cmIND______/ CC______= ______ ( %)Abdomen:Umbilicus:Genitalia:penile length: ______cm ( %)testicular vol.: ______cm ( %)Tanner Stage: ______SKINGeneral description:Freckles - Iris:_____Axillary:_____ Inguinal:_____# CAL spots: _____ Size range:_______cm# Neurofibromas: _____ Size range:_______cmHypopigmented lesions:Other lesions:EXTREMITIES - PROPORTIONSGeneral description:laxity:contratures:digital abnormalities:LOWER segment: ______cmUPPER segment: ______cm (HT-LS)US/LS ratio: ____/____= % ( SD)ARM SPAN: _____ cm WRIST SIGN: ____ THUMB SIGN: ____HAND: R ______cm ( %)L ______cm ( %)MIDDLE FINGER: R ______cm ( %)L ______cm ( %)PALM : R ______cm ( %)L ______cm ( %)FOOT: R ______cm ( %)L ______cm ( %)Finger to Hand: _____/_____ ( %)Hand to Height _____/_____ ( %)Foot to Height _____/_____ ( %)NERVOUS SYSTEMMental status:Cranial nerves:Muscle bulk and tone:Sensation:Motor strength: Deep tendon reflexes:DIAGRAM TO DOCUMENT