Peds: Genetic Evaluations

Question 1

Indications for Genetic Evaluation

Answer 1

• *hx of miscarriages;
• *advanced parental age (35 yrs at date of birth);
• *family hx- birth defects, mental retard., growth retard., neuro. conditions, familial conditions;
• • fetal exposure- medications, illegal substances, radiation, toxic chemicals, intrauterine infections;
• *ethnic background (carrier risk);
• *phenotype (physical findings)- dysmorphic features, developmental delay, short stature, FTT, progress from normal intelligence to mental retardation, deterioration in health, seizures;
• *genotype presentation (genetic lab tests)

Question 2

Facts about Genetic Disorders

Answer 2

• • 80% identified before 6 mos of age;
• *40-45% identified during neonatal period;
• *all associated with some form of cardiac/neuro abnormality;
• *autosomal dominant trait - disorder presents with each generation (bipolar disorder);
• *autosomal recessive trait- disease skips a generation;
• *pedigree hx (genogram)- noted disease pattern in 3 generations by identifying males, females, miscarriages, stillbirths, abnormalities, & diseases;
• *prenatal screening & diagnosis part of genetic assess.;
• *chromosome abnormalities are called syndromes (genetic or spontaneous- can alter growth & dev.)

Question 3

Significance of Punnett Square in Genetics

Answer 3

• • both parents have trait (carriers);
• • 25% chance of a child being affected;
• • 25% chance of a child being unaffected;
• • 50% chance of a child having the disease

Question 4

Trisomy 21 (Down Syndrome)

Answer 4

• • 3rd #21 chromosome;
• • 1:660 births;
• • risk- advanced maternal/paternal age;
• • ranges from mild - severe retardation;
• *phenotype findings- microcephaly, flattened nose, widely separated eyes (hypertelorism), hypotonia, protruding tongue, inner epicanthal skin folds (inner eye), upward slanting eyes, short broad hands/fingers/single palmer crease, & delayed growth/dev.;
• **complications- septal defects, seizures, diabetes mellitus, esophageal/duodenal atresia, hearing/vision impairment, obesity, leukemia, and early dementia (age 30-40 yrs of age)

Question 5

XXY syndrome or Klinefelter’s syndrome

“Calvin Klein is male”

Answer 5

• • XXY karyotype (extra X in males)- extra femaleness;
• • 1:1,000 males;
• *normal @ birth, present @ puberty;
• *common cause of hypogonadism & male infertility;
• *phenotype presentation- tall/lanky stature (abnorm. body proportions), transverse crease, underdeveloped secondary sexual characteristics, gynecomastia, learning disability, & personality impairment;

Question 6

XO Karyotype or Turner’s syndrome

“Tina Turner is female”

Answer 6

• *XO karyotype is most common sex chromosome in females;
• *1:2,000 live births;
• *95% die inutero;
• *known as “puffy babies” due to lymphedema;
• *phenotype presentation- webbed neck (reabsorbed fluid), low hairline, learning disabilities, widely-spaced chest/nipples (shield chest), head/neck abnormalities, HTN (risk of coarctation of aorta), lack secondary sexual characteristics

Question 7

Marfan syndrome

“Michael Marfan loves to swim”

Answer 7

• *inherited connective tissue disorder;
• *impacts skeletal, cardiac, ophthalmic body systems;
• *1:20,000 births;
• *phenotype presentation- tall stature, arm span greater than height, thin extremities/fingers, long narrow face, pectus carinatum (pigeon chest), pectus excavatatum (sunken chest), hyperextension of joints, genu recurvatum (hyperextension of knees), kyphoscoliosis (thoracic spine), high arches/narrow palate, cardiac (aortic regurgitation & mitral valve prolaspe), eye (ectopia lentis -displacement of lens & iridodonesis-vibrating movement of iris with eye movement);
• **contact sports not recommended due to risk of aortic root dissection (aneursym)

Question 8

Tay-Sachs Disease

Answer 8

• *Ashkenazic Jewish descent;
• *1:2,500 live births;
• *normal @ birth; deterioration @ 3 to 6 mos of age;
• *typical progression of disease- decrease tone, listlessness, blindness, deafness, seizures, dementia, vegetative state, death

Question 9

DiGeorge (Velocardiofacial) syndrome

“George Bush shouldn’t drink”

Answer 9

• *congenital defect of parathyroid gland, thymus, and conotruncal region of heart (aortic arch);
• • phenotype presentation- increase susceptibility to infections (due to thymus dysplasia), lateral displacement of inner canthi (eye), short palpebral fissures (medial space between upper/lower eyelids), short philtrum (space between nose and upper lip), micrognathia (receding chin), ear anomalies; aortic arch anomalies, hypoparathyroidism, hypocalcemia (risk of seizures in infancy), and cognitive/behavioral/psychiartic problems;
• **neonatal morbidity/mortality associated to cardiac defects