Developmental Genetics Lecture PDF

Birth Defects & Developmental Genetics Dr. Yasemin Alanay  This lecture will enable you to… Understand that birth defects are common and have a major impact on health Define normal variants, major anomalies, and minor anomalies, and know they may serve as clues to diagnoses...

Birth Defects & Developmental Genetics Dr. Yasemin Alanay  This lecture will enable you to… Understand that birth defects are common and have a major impact on health Define normal variants, major anomalies, and minor anomalies, and know they may serve as clues to diagnoses Know basic errors of morphogenesis. Understand what they are and how they might arise. Know what is meant by syndrome, field defect or sequence, and association Know how teratogens work Define embryogenesis and organogenesis Define basic cellular and molecular mechanisms regulating development  Lecture Outline Impact of birth defects, Role of Clinical Geneticist Dysmorphology/Systematic phenotyping – Major and minor anomalies – Categories of anomalies Malformation, deformation, disruption, dysplasia – Constellations of anomalies Field defects, Association, spectrums, sequence, syndrome Developmental Genetics BIRTH DEFECTS MUST KNOW Congenital anomalies 3% of livebirths MUST KNOW What does a pediatric/clinical geneticist TRY to do when there is baby/child with anomalies? Make a diagnosis Order genetic tests Explain prognosis Follow-up for accompanying morbidities Explaining to family how & why Explain recurrence risk DYSMORPHIC CHILD  Dysmorphology Recognizing “the different”. The study of abnormal form. The medical specialty of evaluating patients with abnormal physical features Nager acrofacial dysostosis (Greek) “Dys” = abnormal, “Morph” = structure – David Smith, USA, 1960 – Evaluates congenital anomalies and structural defects. DYSMORPHIC – A person/child with physical features unexpected for age or ethnicity Normal structure of abnormal size, proportion or shape – Smooth philtrum – Variant palmar creases – Upslanting palpebral fissures Feature not normally present – Ear tag – Extra digit – Supernummerary nipple  Why do we want to make a diagnosis? Neonatal, infant mortality – 20% congenital anomalies – 20% prematurity 30% of pediatric hospitalizations Early diagnosis and management of genetic syndromes Major anomalies – Abnormality that has medical, surgical, or cosmetic significance Minor anomalies – Minor variations of normal morphological features of little of no known medical, surgical, or cosmetic significance – Observed in < 4% of the population  Significance of minor anomalies 15% newborns 1 minor anomaly 3% additional major anomaly anomalies and Rare variants can serve 11 additional major as indicators of 2 minor anomalies anomaly altered morphogenesis and clues to patterns of Extremely rare, 1% malformation ≥3 minor anomalies 90% additional major anomaly Idiopathic mental retardation 80% are minor anomalies 42% have ≥3 anomalies  Teratolog y Spectru Malformatio m n Sequence Disruption CONGENITAL ANOMALIES Deformatio Association n Development Dysplasi al field defect a Syndro me  Terminology-Classification Common variant >4% MINOR VARIANT Problem in Minor variant phenogenesis 4% MINOR VARIANT Problem in Minor variant phenogenesis 4% MINOR VARIANT Problem in Minor variant phenogenesis