Chromosomal disorders

Question 1

what happenes in Meiotic Nondisjunction?

Answer 1

In meiotic nondisjunction two chromosome homologs migrate to the same daughter cell instead of disjoining and migrating to different daughter cells

Fertilization with normal gamete produces Monosomic or Trisomic offspring

Question 2

Many trisomies are ——–?

Trisomy —– is the most common surviving trisomy Trisomies of the ____ and ____ chromosomes are much less common at birth

Answer 2

Many trisomies are not compatible with survival Trisomy 21 is the most common surviving trisomy Trisomies of the 13th and 18th chromosomes are much less common at birth

Question 3

Down Syndrome problems

Answer 3

Mental retardation, GI tract obstructions, Congenital heart defects, Respiratory infections and Leukemia

Question 4

Down Syndrome is?

Answer 4

Trisomy 21 Most common autosomal aneuploidy among live births Extra chromosome 21 contributed by the mother in 95% of cases

Mosaicism: 1-3% of DS cases Usually milder phenotype

Question 5

Down Syndrome features

Answer 5

• Upslanting palpebral fissures (Almond-shaped opening between the upper and lower eyelids)
• Epicanthic (fold Redundant skin of the inner eyelid)
• Low nasal bridge
• Brushfield spot: Light smudgy opacity of the pupil
• Simian crease: A single crease extends transversely across the palm

Question 6

Down Syndrome Mosaicism

Answer 6

Condition in which an individual organism has: Two or more genetically distinct cell lines

Derived from a single zygote Their difference due to: Mutation or Nondisjunction

Question 7

Trisomy 18 characteristics

Answer 7

Edwards syndrome Prevalence: 1/6000 at birth Male/female = ¼

Intrauterine growth retardation

Microcephaly

• Small mouth, palpebral fissures
• Cardiac defects
• Overlapping fingers
• Omphalocele Congenital herniation of viscera into the base of the umbilical cord
• Still born/most die w/in 2 months <10% survive 1 year

Question 8

Patau Syndrome (Trisomy 13) Newborn male with trisomy 13 has? He is? Survival beyond the ____ is rare

Answer 8

Newborn male with trisomy 13 has Cleft palate Atrial septal defect, Inguinal (groin) hernia, and Post axial polydactyly of the left hand

He is Deaf Legally blind

Survival beyond the 1st year is rare

Question 9

Polydactyly

Answer 9

Affecting all extremities, strongly suggests trisomy 13 Extra toes on each foot

An extra finger on the hand of an infant with trisomy 13

Question 10

Trisomy 13 
cleft lip & Cyclopia with a proboscis

Answer 10

baby on the top with cleft lip associated with trisomy 13

baby on the bottom with trisomy 13 has Cyclopia (single eye) and Proboscis (the projecting tissue just above the eye)

Question 11

Monosomy X
 Turner syndrome, karyotype? look for?

Answer 11

Caused by 45,X karyotype

Common at conception Rare among live birth ( Spontaneous abortion)

Mosaicism increase probability of survival to term

reduced Stature, and Swelling (edema) in the ankles and wrists

Question 12

A female with Turner syndrome (45,X) Characteristics

Answer 12

Characteristically broad “webbed” neck

Reduced stature

Poorly developed sexual secondary characteristics Usually infertile because of gonadal dysgenesis

Rarely undergo menarche

Estrogen treatment Around 30-40% mosaic, mostly 45,X/46,XX TS females are sterile

Question 13

Fetal hydrops

Answer 13

when fitus Soft tissues are markedly edematous Body cavities filled with effusions

feature of many chromosomal abnormalities including monosomy X

Question 14

Turner Syndrome: cystic hygroma

Answer 14

Results from failure of lymphatics to form and drain properly

Cystic hygroma forms the “web neck” of TS women

Gray coloration from

prolonged intrauterine 

demise

Question 15

A male with Klinefelter syndrome (47,XXY)

Answer 15

Increased stature, Gynecomastia (enlarged breast), Feminine body shape, Reduced IQ, Usually sterile

Testosterone therapy Mastectomy


Question 16

Trisomy X (47,XXX Karyotype)

Answer 16

Occurs in 1 in 1000 females with benign consequences

Sometimes: Sterility Menstrual irregularity, Mild mental retardation

Mostly result from nondisjunction in the mother Incidence increases with the mother’s age

Females with more X chromosomes exist But more is not better Each additional X chromosome leads to more mental and physical abnormalities

Question 17

hypertelorism

Answer 17

Abnormal distance between two paired organs. in Trisomy X look btw eye brows

Question 18

47, XYY Male Karyotype: Jakob syndrome

Answer 18

These males tend to be taller

Have 10- to 15-point reduction in IQ ? (New studies say no or little difference) ?

Few physical problems

Notorious because 1/30 of prison population compared to1/1000 in the general male population (Studies refute association with violent crime)

Minor behavioral problems: Hyperactivity Attention deficit disorder Learning disabilities

Question 19

XX Male & XY Female

Answer 19

Result from mutation in the SRY (sex-determining region on the Y) or Transfer of SRY from Y to X chromosome during crossing-over between the X & Y chromosomes in male meiosis

Question 20

Albinism

Answer 20

Deficiency of the pigment melanin from Skin Hair Eye can be complete or partial

Question 21

Albinism: Causes, types

Answer 21

Inability to produce or distribute melanin ➔ Albinism

Tyrosine metabolism defects lead to failure to convert it into melanin ➔albinism

Different forms of albinism and several modes of inheritance: Autosomal recessive, Autosomal dominant, X-linked inheritance

Question 22

Complete albinism
 Affected people may have

Answer 22

Affected people may have White hair, skin, and iris

Vision defects, Photophobia, Sunburn easily Should never try to tan

Question 23

Ocular albinism is

Answer 23

Albinism of the eyes only Skin color is normal

Eye color may be in the normal range Brown, blue, green BUT: No pigment in the retina

Question 24

Chédiak-Higashi syndrome

Answer 24

Partial albinism

Autosomal recessive

Silver hair, ocular albinism –Immune system deficiency Infections of lungs, skin & mucosa —EBV affects these children leading to child lymphoma

Nystagmus (jerky eye movement) Muscle weakness Nervous system Tremors Seizures Ataxia/unsteady walking

Question 25

Hermansky-Pudlak syndrome

Answer 25

Partial albinism Oculocutaneous albinism

Autosomal recessive

Platelet storage pool defect ➔ bleeding disorder Ashkenazi Jews and North Puerto Rican

Question 26

Hermansky-Pudlak syndrome Symptoms:

Answer 26

Symptoms: Vision impairment and eye problems (Photophobia Nystagmus Strabismus/crossed eyes) GI involvement with granulomatous colitis (Bleeding, bruising- platelet issue)

Cellular storage: Waxy material accumulation ➔ Damage of the tissue of lungs and kidneys

Question 27

Tuberous sclerosis (TS) characterized by:

Answer 27

Partial albinism

Tuberous sclerosis (TS) characterized by: Peri-ungual fibroma (PUF) on finger

Hypopigmented patch of skin White leaf macule

Question 28

Waardenburg syndrome

Answer 28

Autosomal dominant inheritance

Combined with dystopia of the lacrimal puncta Prominent broad nasal root Hypertrichosis of the medial part of the eyebrows White forelock Heterochromia iridis (absence of pigment in one or both irises) Deafmutism

Question 29

Heterochromia iridis

Answer 29

Autosomal dominant inherited Waardenburg syndrome type I Circumscribed hypopigmentation of the skin Heterochromia iridis Absence of pigment in one iris Sensorineural deafness Dental aberrations

Missense mutation in PAX3 gene Early diagnosis  successful medical care

Question 30

Marfan Syndrome

Answer 30

An autosomal dominant condition A young man with Marfan syndrome, showing characteristically long limbs and narrow face

Arachnodactyly long fingers

Question 31

Diagnosis of Marfan syndrome

Answer 31

Complete family history Medical history

Genetic evaluation

Complete physical examination

Echocardiogram EKG

Annual eye examination Eyes Dislocation of the lens in the eye Nearsighted vision

Skeletal exam Skeleton Tall stature with the span of the arms exceeding height Long fingers and toes Flat feet Curved spine (scoliosis) Chest wall deformity Excessive joint flexibility Reduced elbow extension High arched palate

Question 32

Marfan syndrome’s heart disease

Answer 32

Enlargement of the aorta Leakage of the aortic valve Leakage of the mitral valve

Mitral valve prolapse

Aortic dissection Tearing of the wall of the aorta Result from extreme enlargement of the aorta Rare but very serious