Genetic Evaluations

Question 1

Indications for a Genetic Evaluation

Answer 1

-Advanced maternal age - older than 35 years
-Advanced paternal age - older than 40 years
-History of miscarriages or stillbirths
-Family history of genetic disorders
-Fetal exposure: meds, maternal infections, radiation, ethnic background (sickle cell, PKU, Ashkenazic Jewish), toxic chemicals, drugs & alcohol.

Question 2

What is the prevalence of genetic disorders, if the parents or family do not have any history?

A. 2%
B. 5%
C. 8%
D. 10%

Answer 2

A. 2%
Approximately 2% of all live births are affected by a major genetic malformation.

-About 40%-45% of these accountable genetic disorders are usually diagnosed during the neonatal period and 80% are commonly diagnosed before the child is 6 months old.

Question 3

Phenotype

Answer 3

Physical findings

Question 4

Genotype

Answer 4

Genetic findings

Question 5

Genogram

Answer 5

Go back 3 generations

Question 6

Trisomy 21 (Down Syndrome)

Answer 6

-Extra chromosome in #21
-High-risk with advanced maternal or paternal age
-Phenotypical findings: microcephaly, flat nose, widest eyes, protruding tongue, single palmar crease, Brushfield spots (black dots around eyes)
-Other manifestations: seizures, congenital heart defects, atlanto-axial instability (if they are competing in the special olympics, check C1-C2), early dementia, leukemia, epilepsy
-Management: supportive care, speech and behavioral therapy

Question 7

Klinefelter syndrome (XXY Syndrome)

Answer 7

-Most common sex-chromosome anomaly in males
-Extra X chromosome
-Only affects males
-Not hereditary
-Only genetic disorder without cardiac defects
-Patients appear normal at birth with s/s presenting at puberty
-This is the most common cause of hypogonadism and infertility in men
-Phenotypical findings: Tall, abnormal body proportions (long arms), gynecomastia, personality impairment
-Management: Refer to endo for infertility and gynecomastia, testosterone replacement therapy, and fertility treatment

Question 8

Turner Syndrome (XO Karyotype)

Answer 8

-Most common sex-chromosome anomaly in females
-Missing or altered X chromosome
-Most embryos with Turner syndrome do not survive to term (95%)
-Phenotypical findings: Webbed neck, low hairline, “shield”-shaped chest (widely spaced nipples), cardiac defects, infertility
-Management: Refer to endo, estrogen-repacement therapy

Question 9

Marfan Syndrome

Answer 9

-Abraham Lincoln
-Inherited connective tissue disease, affects skeletal, cardiac, and ophthalmic system (ectopia lentis, increased chance of retinal detachment and glaucoma, which can lead to blindness)
-Phenotypical findings: Tall stature, large wing-span (wider than height), pectus carinatum (out) or excavatum (in), hyperextension of joints, cardio (aortic regurgitation, mitral valve prolapse, aortic root dilation, and aneurysm), eyes (iriododenosis), kyphoscoliosis
-Management: Refer to cardio. May need BB to prevent aortic rupture.

Question 10

Tay-Sachs Disease

Answer 10

-Affects the Ashkenazic Jewish population
-Progressive muscle tone - leads to vegetative state and eventually death
-Patients present normal at birth and begin deteriorating by 3-6 months
-Phenotypical findings: Cherry red macula (hallmark sign), blind, deaf
-Management: Neuro, palliative care

-Destroys nerve cells in the brain and spinal cord
-Can produce symptoms of dementia in pediatric patients
-HEXA gene mutation

Question 11

DiGeorge (Velocardiofacial) Syndrome

Answer 11

-Affects parathyroid, thymus and heart (aortic arch anomalies)
-Deletion of the 22nd chromosome
-Parathyroid controls calcium and phosphorus
-Thymus helps fight infections
-Phenotypical findings: Flat faces - lateral displacement of inner acanthi and short palpebral fissures, congenital heart defects, seizures - hypocalcemia
-Management: Monitor for infections, seizures, and hypocalcemia

Question 12

HEXA Gene Mutation

Answer 12

Affects:
-Tay-Sachs - Ashkenazic Jewish
-French Canadian
-Lousiana Cajun