genetics.pdf

Unit 3 Genetic testing in the neonates and children Screening for o Congenital abnormalities o Developmental delay o Dysmorphism Congenital abnormalities. A congenital abnormality is a condition, whic...

Unit 3 Genetic testing in the neonates and children Screening for o Congenital abnormalities o Developmental delay o Dysmorphism Congenital abnormalities. A congenital abnormality is a condition, which is present at the time of birth, which varies from the standard presentation. Types of congenital anomalies. 1. A limb anomaly is called dysmelia. These include all forms of limb anomalies such as Amelia, ectrodactyly, phocomelia, polymelia, polydactyl, syndactyly, polysyndactyly, oligodactyly, brachydactyly, achondroplasia, congenital aphasia or hypoplasia etc. 2. Congenital anomalies of heart include: patent ductus arteriosus, atrial septal defect, ventricular septal detect and tetralogy of fallot etc. 3. Congenital anomalies of the nervous system include neural tube defect, Arnold chiani malformation, macrocephaly, polymicrogyria etc. 4. Congenital anomalies of the gastrointestinal system include numerous forms of stenosis, atresia and imperforate etc. Causes of congenital anomalies. 1. Unknown cause( idiopathic): the vast majority of congenital abnormalities have no known cause. 2. Genetic and environmental problems: spina bifida, cleft lip and palate are types of congenital abholmalties that may occur when there is genetic tendency for the condition with exposure to certain environmental toxin within the womb during critical stages of pregnancy. 3. Conditions during first trimester of pregnancy: certain disease or illnesses during pregnancy particularly during first nine weeks can cause congenital abnormalities. 4. Inherited causes: chromosomes are the genetic structures inherited from one generation to the next. 1 Screening for congenital abnormalities. Neonatal screening Neonatal testing can be performed to diagnose disorder or screen for a potential pathological conditions. This can be done by testing newborn blood sample. Neural tube detect: recommended screening test is maternal serum AFP and USG and CT. Phenylketonuria: blood test and urine test for early diagnosis in neonates. Congenital hypothyroidism: testing for the level of thyroxine (T4) or thyroid stimulating hormone (TSH) or both. Maple syrup urine disease: diagnosis is made through serum level of branched chain amino acids. Galactosaemia: screening involve urine or serum assessment for galactose. Cystic fibrosis: prenatal DNA testing can identify the carries. Neonatal diagnosis involves testing for high sweat chloride levels. Trisomies: prenatal testing can be made through amniocentesis,CVS, AFP, USG, triple marker test. Genetic screening. Detailed physical examination. Blood biochemistry Molecular genetic tests. Fluorescence in situ hybridization. USG ECG Radiological examination. Developmental delay. Child development refers to the process in which children go through changes in skill development during predictable time periods called developmental milestones. Developmental delay is a significant lag in a child’s physical, cognitive, behavioral, emotional or social development in comparison with norms. Risk factors for developmental delay. Risk factors for developmental problems fall into two categories. I. Genetic factor: children are placed at genetic risk by being born with a genetic or chromosomal abnormality. 2  II. Environmental factors: environmental risk results from exposure to harmful agents either before or after birth, can include things like poor maternal nutrition or exposure to toxins or infections that are passed from mother to her baby during pregnancy. Warning signs of developmental delay. 1. Behavioral warning signs. Does not pay attention or stay focused on an activity for as longer times as other children of the same age do. Focuses on unusual objects for long periods of time. Enjoys this more than interacting with others. Avoids or rarely makes eye contact with others. Gets unusually frustrated when trying todo simple task that most children of the same age can do. Shows aggressive behaviors and acting out, and appears to be very stubborn compared with other children. Display violent behaviors on daily basis. Stares into space, rocks body or talks to self, more often than other children of the same age. Does not seek love and approval from a caregiver or parent. 2. Gross motor warning signs. Has stiff arms and legs. Has a floppy or limp body posture compared to other children of the same age. Use one side of the body more than the other. Has a very clumsy manner compared with other children of the same age. 3. Hearing and Vision warning signs Seems to have difficulty following objects or people with eyes. Talks in a very loud or very soft voice. Ears appear small or deformed. Screening of developmental delay. Developmental screening test is a quick and general measurement of skills. Its purpose is to identify children who are in needed of further evaluation. A screening test is only meant to identify children who might have problems. Commonly used tools are: I. Battle developmental inventory screening test. It can be used to screen children aged 12 – 96 months, using a combination of direct assessment, observation and parental interview. 3 II. Bayley infant neurodevelopmental screener It is designed for screening high risk infants aged 3-24 mouths.it uses 10 -13 directly elicited items per 3-6 month range to assess neurodevelopmental skills and developmental accomplishments. III. Child development inventories. The child development inventory, formerly known as Minnesota child development inventory, was created to provide a systematic, standardised method for parents to report on their children's strengths, problems and present development. The original 300 item instrument has been broken down into instruments that apply to three age intervals. The CDI measures a child’s development in eight area namely social, self-help, gross metas, fine motor, expressive language, language comprehension, letters and numbers. IV. Denver developmental screening test. It was introduced in 1967. Denver II is the most commonly used developmental screening tool.it combines direct observation and parental report. The tool consists of 125 items, organized into four developmental domains namely gross motor, fine motor, language and personal/ social. Dysmorphism. Definition. Dysmorphism means disturbed structure of the body. Dysmorphology is the study of dystrophic features, their origins and proper nomenclature. Dystrophic features develop during embryogenesis or morphogenesis. They are invariably present from birth, although some are not immediately apparent at birth. Classification. The dysmorphic features are classified depends on the origin into: A). Malformation (abnormal development) B). Disruptions (damage to previously normal tissue) C). Deformations (damage caused by some external force). D). Dysplasias (abnormal growth or organization within a tissue) 4 Etiology Chromosomal or genetic causes of these anomalies include inheritance of abnormal genes from the parents, as well as new mutations in one of the germ cells that gave rise to the fetus. Environmental causes of dysmorphic anomalies are referred to as teratogenic. Teratogens can include dietary deficiencies, toxins, or infections. Unknown causes.in some situations even can be established for a defect. Common dysmorphic syndromes. I. Syndromes with craniofacial dysmorphism. a) Mobieus sequence. b) Frontonasal dysplasia sequence. c) Goldenhar syndrome. d) Craniosyntoses syndrome. e) Carpenter syndrome. II. Syndromes with physical overgrown. a) Fragile X syndrome. b) Marshall- smith syndrome. c) Weaver smith syndrome. III. Syndromes with CNS and neuromuscular defects. a) Prader willi syndrome. b) Myotonic dystrophy syndrome. IV. Syndromes with chromosomal abnormalities. a) Down syndrome. b) Edward syndrome c) Patau syndrome. d) Turner’s syndrome. Screening of dysmorphism. Detailed physical examination. Blood biochemistry of children. Molecular genetic tests. Fluorescence in situ hybridization. (FISH) Ultrasonography Echocardiography. Electro cardiogram. Radiological examination 5