EMBRYOLOGY

o Gregor Mendel – father of genetics

o Genetic Laws
o Segregation
o Assortment
o 46 chromosomes = 44 autosomes + 2 sex chromosomes (X/Y)
o Paired, 1 from father, 1 from mother
o Similar – alleles
o Disimilar – non-alleles
o Dominant gene – expressed even if only 1
o Recessive gene – expressed only if 2
o Pedigree for consultand or counseltee (approaches you)
o 3 generations – I, II, III
o Sex using symbols: circles (♀), squares (♂) or diamonds (unknown), numbers inside symbol = quantity
o Marriage – solid horizontal line, Illegitimate – dotted line, Consanguinous – double line
o Index patient – pointed by arrow
o Others:
 Cancer – dot inside symbol
 Heterozygote – half-shaded symbol, homozygote – shaded symbol
 Dizygotic twins – diagonal branching from parents
 Monozygotic twins – diagonal branching from parents with line between them
 Dead (at birth?) – line from parent has dash
 Degree of affinity – 1° (father, mother), 2° (aunts, uncles), 3° (cousins)

Autosomal Dominant Inheritance

1. Affected person has affected parent, except with mutations
2. Affected person’s offspring have 50:50 normal and affected proportion
3. Normal children of affected parent usually has normal offspring
4. Considerable variation of clinical severity of disease, both sexes affected

Recessive Inheritance
1. appears in sibs
2. 25% chance
3. for rare disease, consanguineous, common conditions = unrelated
4. both sexes affected

X-Linked dominant
1. at least 1 parent affected
2. Both sexes affected
3. Affected ♀ transmits to half of her daughters and half her sons

X-Linked Recessive
1. Both sexes affected
2. Homozygous ♀ = all sons affected, all daughers heterozygous
3. Heterozygous ♀ = half of sons, half of daughters
4. Affected ♂ = transmit to all daughters (as carriers), none to sons

Y-Linked / Holandric
1. males only
2. Transmitted to all sons, none to daughters

Autosomal Disorders
o Cytogenetics – chromosomes and abnormalities
o Sample collection: Blood / bone marrow  trigger mitosis  stop growth  add saline  arrange chr by size

Syndrome Notes
Aneuploidy alteration in chr number
1.5/1000 births, round fascies, widespaced eyes, epicanthal folds, upturned snub nose, ↑ congenital heart disease, simean
Down’s (Trisomy
crease, change in hands and feet, dermal ridge, mental retardation, max age of 50’s
21)
Due to late maternal age (eggs are as old as mother), Chr 21 non-disjunction = 3 Chr21
Pataus (Trisomy 0.1/1000 births, 3 Chr13, holoprosencephaly, severly mentally retarded, shorter lifespan, death at infancy
13)
Edward (Trisomy 0.2/1000 births, 3 Chr18, poorly developed lower jaw, abnormal ears, triangular face, flexion deformities of the wrist, severed
18) CHD, shorter lifespan
Structure deletion, translocation, ring chr
Cri-du-chat Deletion of Chr5p (short arm), peculiar cry (meow) due to larynx softening (laryngomalachia) but eventually normalizes,
(Delete Chr 5) hypertonic, peculiar fascies, mentally retarded
Wolf’s (Delete Deletion of Chr4p (short arm), facial asymmetry, micrognathia, mental retardation, hypertonicity, hypospadias, seizures
Chr 4)

Sex Chromosome Abnormalities

Syndrome Notes
Phenotypic Females

Infantile uterus, cubitus valgus, webbed neck, short stature, low hairline, shield-like chest, high arch palate, low set
Turner’s (XO) ears, fish mouth, hypoplastic nipples, lymphedema of hands / feet, coarctation of aorta, abnormal auricle, loose neck
folds (neonatally), no 2ndary sex characteristics, no ovarian follicle elements, false accessory ovaries
Trisomy X
Tall, good-looking, slight mental slowness, skeletal abnormalities, prone to psychiatric illness
(XXX)

Poly X (> 3) Multiple anomalies, mental retardation, more X = more problems

 Phenotypic Males
Tall, sexual infantilism, long extremities, undescended testes, hypospadia, infertility, sparse pubic hair, testicular
Kleinfelter’s
pathology (hyalinization, sclerosis, obliteration of seminiferous tubules, azospermia)
(XXY)
Poly X(Y) = multiple anomalies, mental retardation

XXY Seizure disorders, sociopathic personality

Intersex Mosaic (XX/XY), Mosaic (XO/XY), Mosaic (XO/XX/XXYY/XXXXY)

Hermaphrodite
o True Herms – Male or Female Habitus (ovotestis (ovary with seminiferous tubules), hypertrophied clitoris (penis-like))
o Pseudo Herms – vagina opening into perineum, bifid scrotum, has penis, hypoplastic testis
o Negative Male (XY) – female, vagina ends blindly
o Virilism + Marked Hirsutism – female, hairy, adrenal cortex hyperplasia, hypertrophied clitoris, urethrovaginal meatus (vagina opens into urethra),
hypoplastic ovary