Clinical Diagnosis

Question 1

Trisomy 21 Features (Signs and Symptoms)

Answer 1

Down Syndrome:
-Intellectual Disability
-Short Stature
-Depressed nasal bridge, upslanting palpebral fissures, epicanthal folds
-Congenital heart defects
-Single palmar crease
-Develop changes similar to Alzheimer disease at a relatively young age

Question 2

Genetic Causes of Down Syndrome

Answer 2

Non-disjunction during meiosis
*May also result from Robertsonian translocation

Question 3

Trisomy 18 Features

Answer 3

Edwards Syndrome
-Clenched fist, overlapping of fingers
-Rocker bottom feet
-Congenital heart defects
-Low-set ears, small lower jaw (micrognathia)
-Microcephaly
-Intellectual disability

Question 4

Genetic mechanism of Trisomy 18

Answer 4

Nondisjunction during oogenesis

Question 5

Trisomy 13 Features

Answer 5

Patau syndrome
-Polydactyly
-Cleft lip and palate
-Microphthalmia
-Microcephaly
-Intellectual disability
-Cardiac anomalies (VSD or ASD)

Question 6

Genetic mechanism of Patau syndrome

Answer 6

-Nondisjunction during oogenesis

Question 7

Names of Sex chromosome Aneuploidy

Answer 7

-Turner Syndrome (45, X)
-Klinefelter Syndrome (47, XXY)

Question 8

Genetic basis of 45, X

Answer 8

Turner Syndrome: X chromosome monosomy
-Usually due to nondisjunction during spermatogenesis

Question 9

Features of Turner Syndrome

Answer 9

-Short stature
-Webbed neck, cystic hygroma birth (neck swelling)
-Primary amenorrhea
-Gonadal dysgenesis
-“Streak ovaries”
-Lymphoedema of hands and feet
-Many are mosaic: many have no Barr body (Inactivated X-chromosome)

Question 10

Genetic mechanism of 47, XXY and name

Answer 10

Klinefelter syndrome
-Nondisjunction during meiosis
-Some individuals may be mosaic

Question 11

Features of Klinefelter syndrome

Answer 11

-Gynecomastia
-Female distribution of hair
-Infertility and testicular atrophy due to low levels of testosterone
-Feminization of features

Question 12

Trisomy Rescue

Answer 12

One way that a person could be mosaic for Down Syndrome:
1) Non-disjunction may occur in the ovum during oogenesis, and fertilization by a normal sperm leads to trisomy 21 in the conception
2) During a post-fertilization mitosis, one of the extra chromosome 21 is evicted during cell division

Question 13

Reciprocal Translocation

Answer 13

Exchange of genetic material between non-homologous chromosomes

Question 14

What are the effects of reciprocal translocation in carriers?

Answer 14

Somatic cells: 1) silent
2) Transformation to cancer and increased growth rate of cells

Question 15

Cri-du-chat Syndrome

Answer 15

Deletion of chromosome 5p
-High pitched, cat-like cry
-Micrognathia which influences the cat-like cry and later, speech problems
-Severe intellectual disability
-Microcephaly
-Hypertelorism (widely spaced eyes)

Question 16

22q11.2 Deletion Syndrome

Answer 16

Velocardiofacial syndrome or DiGeorge Syndrome
-CATCH 22 :
-Congenital heart defects
-Absence of thymus (thymic aplasia): might cause immunological problems
-Cleft lip & palate, maybe speech difficulty
-Hypocalcemia
-Learning disability
-Facial anomalies
-Increased risk for schizophrenia

Question 17

Wolf-Hirschhorn syndrome (WHS)

Answer 17

-Deletion of ch 4p
-Seizures
-Skeletal abnormalities and congenital heart defects
-Spectrum of intellectual and developmental delay, mild to severe
-Facial anomalies, widely spaced eyes, high-arched eyebrows, broad and flat nasal bridge often described as similar to a roman helmet, short philtrum, downturned mouth, small chin

Question 18

Beckwith-Wiedemann Syndrome (BWS) Features

Answer 18

-Macroglossia (enlarged tongue)
-Birth weight and length greater than 90 percentile
-Abdominal wall defects such as umbilical hernia
-Ear creases or pits
-Neonatal hypoglycemia
-Increased risk of cancer

Question 19

Albinism is due to a deficiency of what?

Answer 19

The pigment melanin due to lack of activity of the enzyme tyrosinase

Question 20

Alkaptonuria is due to:

Answer 20

The buildup of a toxic substance due to an enzyme deficiency:
-black urine disease, is a very rare inherited disorder that prevents the body fully breaking down two protein building blocks (amino acids) called tyrosine and phenylalanine. It results in a build-up of a chemical called homogentisic acid in the body.

Question 21

Phenylketonuria (PKU) is due to:

Answer 21

Defect of phenylalanine metabolism due to deficiency of the enzyme phenylalanine hydroxylase
-Phenylalanine and its metabolites accumulate to toxic levels
-There is also a deficiency of downstream products of phenylalanine including the neurotransmitter DOPA and the pigment melanin