Dysmorphology and Chromosomal Abnormalities PDF

Dysmorphology Chromosomal & Teratogenic Disorders Amanda G. Fleenor, MMS, PA-C Clinical Skills II Instructional Objectives Recognize and apply dysmorphology terminology Identify and recognize history and physical exam findings associated with specific chromosomal condit...

Dysmorphology Chromosomal & Teratogenic Disorders Amanda G. Fleenor, MMS, PA-C Clinical Skills II Instructional Objectives Recognize and apply dysmorphology terminology Identify and recognize history and physical exam findings associated with specific chromosomal conditions and diseases. Identify and recognize history and physical exam findings associated with specific teratogenic conditions and diseases. Dysmorphology Terms Terms pertaining to the Face and Head Brachycephaly Condition in which head shape is shortened from front to back along the sagittal plane The skull is rounder than normal Terms pertaining to the Face and Head Canthus The lateral or medial angle of the eye formed by the junction of the upper and lower lids Terms pertaining to the Face and Head Columella The fleshy tissue of the nose that separates the nostrils Terms pertaining to the Face and Head Glabella Bony midline Prominence of the brows Terms pertaining to the Face and Head Nasal alae The lateral flaring of the nostrils Terms pertaining to the Face and Head Nasolabial fold Groove that extends from the margin of the nasal alae to the lateral aspects of the lips Terms pertaining to the Face and Head Telorism – Pertaining to the spacing of the eyes Ocular Hypertelorism - Increased distance between the pupils of two eyes Ocular Hypotelorism – Decreased distance between the pupils of two eyes Terms pertaining to the Face and Head Palpebral Fissure The shape of the eyes based on the outline of the eyelids Terms pertaining to the Face and Head Philtrum The vertical groove in the midline of the face between the nose and the upper lip  Terms pertaining to the Face and Head Plagiocephaly Condition in which the head shape is asymmetric in the sagittal or coronal planes Can result from asymmetry in the suture closure or from asymmetrical brain growth Can also see positional Plagiocephaly Terms pertaining to the Face and Head Scaphocephaly Condition in which the head is elongated from front to back in the sagittal plane Most normal skulls are slightly scaphocephalic Terms pertaining to the Face and Head Synophrys Eyebrows that meet in the midline Terms pertaining to the Face and Head Telecanthus A widened space between the medial canthus (inner canthal distance) Terms pertaining to the Extremities Brachydactyly Condition of having short digits Terms pertaining to the Extremities Camptodactyly Condition in which a digit is bent or fixed in the direction of flexion “trigger finger” type appearance Terms pertaining to the Extremities Clinodactyly Condition in which a digit is crooked and curves toward or away from adjacent digits Terms pertaining to the Extremities Hypoplastic Nail An unusually small nail on a digit Terms pertaining to the Extremities Melia - Suffix meaning “limb” Amelia – missing limb Brachymelia– shortened limb Terms pertaining to the Extremities Oligodactyly A deficiency in the number of digits Terms pertaining to the Extremities Polydactyly The condition of having six or more digits on an extremity Terms pertaining to the Extremities Syndactyly The condition of having two or more digits at least partially fused Chromosomal Disorders Trisomy 13 Trisomy 18 Trisomy 21 (Down’s Syndrome) Klinefelter’s Syndrome (XXY) Turner’s Syndrome (XO) Cri Du Chat Syndrome Fragile X Syndrome Trisomy 13 AKA – Patau Syndrome 47, XX +13 or 47, XY +13 Occurs in 1:12,000 live births Usually fatal in 1st year of life – 8.6% survive beyond 1st birthday Trisomy 13 Key features: SGA and microcephalic Midline facial defects – cyclopia, cebocephaly, cleft lip and palate Sloping forehead, small and malformed ears, micro- or anopthalmia Polydactyly, clinodactyly, clubfeet or rocker- bottom feet Aplasia Cutis Congenita - punched out scalp lesion over right or left occiput When accompanied by polydactyly and some or all of the above features, this is essentially pathognomonic of trisomy 13 Trisomy 13 – Other Clinical Manifestations Head and Face Scalp defects (ex. Cutis aplasia Micropthalmia, corneal abnormalities Cleft lip and palate in 60-80% of cases Microcephaly Sloping Forehead Capillary Hemangiomas Deafness Chest Congenital Heart Disease (VSD, PDA, and ASD) in 80% of cases Thin posterior ribs (missing ribs) Extremities Overlapping fingers and toes (Clinodactyly) Polydactyly General SGA Severe developmental delays and prenatal and postnatal growth retardation Renal Abnormalities Two day old girl with Trisomy 13 (Patau syndrome). (a) Craniofacial features include microcephaly with sloping forehead, supraorbital creases, and broad triangular nose. (b) Low set pinnae with abnormal helices. (c) Postaxial polydactyly. (d) "Rocker bottom feet" (prominent calcanei). (e) Another child Trisomy 13 with cutis aplasia of the scalp. Source: Clinical Cytogenetics, Medical Genetics: An Integrated Approach Citation: Schaefer G, Thompson, Jr. JN. Medical Genetics: An Integrated Approach; 2017 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=173744329 Accessed: January 17, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved Trisomy 18 AKA – Edwards Syndrome 47, XX +18 or 47, XY +18 The second most common autosomal Trisomy Occurs ~ 1:7,500 live births 50% with Renal anomalies – horseshoe kidney Hypothyroidism 5x more likely Turner Syndrome Streak gonads (gonadal dysgenesis) instead of well developed ovaries leads to estrogen deficiency Prevents development of secondary sexual characteristics Amenorrhea Infertility is not corrected by estrogen replacement Assisted Reproductive Technology Cri Du Chat Syndrome Deletion on short arm of chromosome 5 Larger deletion associated with more severe expression Characteristic “cat like” dry during infancy due to tracheal hypoplasty Key Features Low birth weight, postnatal failure to thrive, hypotonia, developmental delay, microcephaly craniofacial dysmorphism – ocular hypertelorism, epicanthal folds, downward obliquity of the palpebral fissures, low-set malformed ears Clefts of the lip and palate, congenital heart disease, and other malformations may be seen Young girl with Cri-du-chat syndrome (5p-). (Reprinted with permission from Brooker RJ: Genetics: Analysis & Principles, 3rd ed. New York: McGraw-Hill, 2008.) Source: Clinical Cytogenetics, Medical Genetics: An Integrated Approach Citation: Schaefer G, Thompson, Jr. JN. Medical Genetics: An Integrated Approach; 2017 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=173744354 Accessed: January 17, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved Fragile X Syndrome (FRAX) AKA – Martin-Bell Syndrome Disorder caused by expansion of trinucleotide repeats ~1:2000 children The most common cause of inherited mental retardation Genetic males affected more severely than genetic females  Fragile X Syndrome (FRAX) Key Features Craniofacial findings – Large head, prominent forehead, jaw, and ears Macro-orchidism – testicular volume twice normal in adulthood Connective tissue abnormalities Mitral valve prolapse Characteristic neurobehavioral profile - mental retardation (from mild to profound), autism spectrum disorder, pervasive developmental disorder Teratogenic Disorders ~ 6.5 of all birth defects are attributed to teratogens, which are chemical, physical, or biological agents that have the potential to damage embryonic tissue and result in 1 or more congenital malformations Prescription and nonprescription drugs, intrauterine infections, maternal diseases, environmental substances Fetal Alcohol Syndrome 10-20:1000 children Most common teratogenic syndrome To cause “full blown” fetal alcohol syndrome, pregnant women must drink at least 6oz alcohol each day during pregnancy Animal studies have suggested that even a single episode of consuming the equivalent of two alcoholic drinks during pregnancy may lead to loss of fetal brain cells and milder signs and symptoms one drink = 12 oz of beer, 5 oz of wine, or 1.5 oz of “hard” liquor  Fetal Alcohol Syndrome Key Features: Prenatal and postnatal growth retardation typically results in a height or weight below the 10th percentile for age and race Characteristic Facial Features- midface hypoplasia, micropthalmia, short palpebral fissures, ptosis, underdeveloped ears (railroad appearance), smooth philtrum, thin upper lip, CNS – Findings – Microcephaly, intellectual impairment, cognitive impairment, developmental delay (global), irritability in infancy, hyperactivity Skeletal abnormalities –clinodactyly of the fifth fingers, camptodactyly, “hockey stick” palmar creases Functional Problems: Myopia, astigmatism, hearing loss Cardiac Defects Fetal Alcohol Syndrome  Fetal alcohol syndrome. A. At 2½ years. B. At 12 years. Note persistence of short palpebral fissures, epicanthal folds, flat midface, hypoplastic philtrum, and thin upper vermilion border. (From Streissguth, 1985, with permission.) Source: Teratology, Teratogens, and Fetotoxic Agents, Williams Obstetrics, 24e Citation: Cunningham F, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS. Williams Obstetrics, 24e; 2013 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=59791355 Accessed: January 17, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved References Clinical Cytogenetics. In: Schaefer G, Thompson, Jr. JN. eds. Medical Genetics: An Integrated Approach. McGraw-Hill Education; 2017. Cunningham F, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS. Williams Obstetrics, 24e; 2013 Marcdante, Karen J., and Waldo E. Nelson. Nelson Essentials of Pediatrics, 6e; 2011 “Online Research Resources Developed at NHGRI.” National Institutes of Health, U.S. Department of Health and Human Services, elementsofmorphology.nih.gov/ Meeks NL, Kochhar A, Duis J, Saenz M. Genetics & Dysmorphology. In: Bunik M, Hay WW, Levin MJ, Abzug MJ. eds. Current Diagnosis & Treatment: Pediatrics, 26e. McGraw-Hill Education; 2022. Schaefer G, Thompson, Jr. JN. Medical Genetics: An Integrated Approach; 2017 Wattendorf, DJ., Muenke, M. Fetal Alcohol SpectrumDisorders. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. Am Fam Physician. 2005 Jul 15;72(2):279-285.