Fetal Alcohol Syndrome

• severe mental retardation
• characteristic facial features include small head, flat midface, epicanthal folds, thin upper lip

Thalidomide

• used a sedative and caused phocomelia (seal limbs)

Fetal Alcohol Effect

low birth weight and IQ

Indirect microbial infection

• the mother is infected
• low birth rate
• growth retardation
• premature

Direct microbial infections

• The fetus is infected
• TORCH
  • Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes

• Rubella

• Infection in 1st trimester is the most serious
• Causes deafness, microencephaly, heart defects, ocular abnormalities

"Cri du Chat"

• Deletion of chromosome 5
• Characteristics: small head, reduced muscle tone, malformed vocal cords, so they have a shrill cry like a cat

WAGR Syndrome

• Loss of part of short arm of chromosome 11
• Wilms tumor, Aniridia, Genital malformation, mental Retardation

Retinoblastoma

• Loss of part of long arm of chromosome 13
• Rb is a tumor suppressor gene

Chronic myelogenous leukemia

• translocation between chromosome 21 and 22 or 21 and 14--> zygote has normal # of chromosomes, but 22 or 14 is carries extra info from 21.

Non-disjunction

failure of chromosomes to separate during meiosis

mosaic

• non-disjunction can occur during mitotic divisions and only SOME cells will be affected
• mosaics are less severely affected.

Trisomy 21 Down Syndrome

• 95% of cases due to non-disjunction, mainly maternal in origin
• 5% due to translocation
• 1% are mosaics
• Ocular conditions: keratoconus, strabismus, nystagmus
• Congenital heart disease affects 50% of DS patients
  

Trisomy 13 (Patau's Syndrome)

• more severe than Down Syndrome
• death typically occurs by 6 months of age
• mosaics may survive into adulthood

XO Turner's Syndrome

• XO monosomy
• Rx w/ growth hormones to achieve normal stature and sex steroids to promote secondary sexual traits

Klinfelter's syndrome

• XXY TRISOMY
• male but with some female features
• with the presence of 3-4Y, they have mental retardation

Reduced Penetrance

• parents have an abnormal gene but it does not manifest the disease
• However, these genes can be passed down to children

Familial Hypercholesterolemia

• AUTOSOMAL DOMINANT
• defective gene for low-density lipoprotein (LDL) receptor--> LDL is not recycled to the liver and cholesterol cannot be delivered to tissues
• atherosclerosis, and xanthomas (deposits of LDL w/ macrophages)

Marfan Syndrome

• AUTOSOMAL DOMINANT
• defective gene FBN1 on chr. 15, codes for fibrillin 1
• Sx: subluxation of lens, weak heart valves, tall, long extremities

Cystic Fibrosis

• AUTOSOMAL RECESSIVE
• aka mucoviscidosis
• Mutated CFTR gene on chr. 7, codes for protein forming cAMP dependent-chloride transport channel
• highly viscoid secretions leads to blockages
• can have recurrent chest infections leading to bronchiectasis

Hemophilia

• X-LINKED RECESSIVE
• bleeding disorder due to deficiency of clotting factors
• A severe disease can cause hemarthrosis--hemmorrage in joints leading to deformities

Phenylketonuria

• AUTOSOMAL RECESSIVE
• deficit of phenylalanine hydroxylase leading to an accumulation of phenylalanine
• causes lack of pigmentation, musty odor, long term nerve damage

Muscular Dystrophy

• X-LINKED RECESSIVE
• mutation of the dystrophin gene
• without dystrophin, muscle cells cannot maintain correct form during contraction
• 2 Types:
  • Duchenne--very severe, muscle wasting begins in utero
  • Becker's--muscle weakness begins in late childhood

Hypophosphatemic osteomalacia

• X-LINKED DOMINANT
• very rare
• failure of bone mineralization due to defective phosphate resorption in kidney

Leber's hereditary optic neuropathy

• MITOCHONDRIAL GENE DISORDER
• come from maternal line
• degeneration of optic nerve leading to bilateral loss of central vision.
• mutation is in the NADH hydrogenase of ETC.

Fragile X Syndrome

• defective FMR1 gene--presence of repeat sequences (ex CAG) prevents transcription of FMR1 gene
• most common form of hereditary mental retardation in males--short attention span, aggressive behavior

Multifactorial (polygenic) inheritance

• several genes are involved
• mutations result in predisposition to the disease then environmental factors influence the expression and severity of the disease