CHAPTER 3 & 6 - hemorrhage & fetal diseases

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• PLEIOTROPY many phenotypic effects of a single gene mutation
• GENETIC HETEROGENITY situation when mutations at several genetic loci lead to the same trait
• POLYMORPHISM a genetic variant that has at least two alleles and occurs in at least 1% of the population
• polyploidia multiples of haploid number
• aneuploidia not exact multiple of n , n+1, n-1
• mosaicism >2 populations of cells with different complements of chromosomes in the same individual
• Translocation transfer of a part of one chromosome to antother
• Isochromosomes the horizontal division of the centromere
• Deletion loss of a portion of a chromosome
• Inversion two intersitial breaks, the segment reunites after a complete turnaround
• Klinefelter syndrome XXY, nondisjunction, small penis, no hairs, narrow shoulders, wide hips, hypogonadism, bad spermatogenesis, risk of breast and gonadal cancer
• Turner's syndrome monosomy, 45X, mosaic, webbed neck, hypogonadism, ammenorhea, strea uterus,
• point mutations substitution of a single nucleotide base ( sickle cell anemia)
• "nonsense mutations" change of amino acid codon to a chein termination codon= no protein is formed
• frameshift mutations insertion/deletion that alters the whole reading frame of DNA
• trinucleotide repeat mutations amplification of a sequence of three nucleotides, mainly guanine and cytosine
• epigenetic changes modulation of gene/protein expression by methylation ( silencing) of cytosine residues at gene promoters or by regulation of family of histone proteins
• familial hypercholesterolemia autosomal dominat, muation of LDLR gene, poor synth. of LDL-rec/transport/LDL binding, acc. of LDL cholesterol in plasma, artherosclerosis occurance,
• ADPKD 1/1000 infants, symptoms in 40 y/o, cysts in liver, pancreas, seminal vesicle, arachnoid membrane,
• Neurofibromatosis (von recklinghause) 1/3000 infants, hyperactivity of RAS protein, incr. cell growth, lisch nodules, optic glioma, learning disability, fragile bones, scoliosis
• Marfan syndrome FB1 gene mutation, fibrillin in microfibrillin defective, 80%familial, heart, skeleton, eyes, ciliary zonulae, ligaments, aorta defective, arachnodactyly, ectopia lentis
• CYSTIC MEDIONECROSIS fragmentation of elastic fibers in the tunica media of aorta that predisposes to aortic dissection and aneurysmal dilation
• Cystic fibrosis mutation of CFTR gene, loss of epitehelial Cl-channel protein, meconium ileus exocrine gland, repsiratory, GI, reproductive system problems
• Alpha 1 antitrypsin deficency mutations in the serpina gene 1, encodes for protein which protects lungs from attack by eznyme neutrophil elastate, leads to COPD, liver cirrhosis
• Phenylketonuria lack of PAH that converst phenyalanine to tyrosine, acc. of phenylalanine,
• Galactosemia disorder of galactose metabolism
• Lysosomal storage diseases Gaucher disease, Tay sachs disease, Fabry disease, Niemann-Pick diseases)- lack of a lysosomal enzyme leads to accumulation of insoluable metabolites within the lysosomes
• Mucopolysacharidoses defective degradation of mucopolysacharides
• Glycogen storage diseases deficiency of enzyme involved in glycogen synthesis or degradation
• Duschene muscular dystophy 1/500, a protein that helps keep muscle cells membrane intact, caused by an absence of dystrophin,
• Wilms tumor Common child tumor in kidney, associated w/ WAGR syndrome, Denys-drash, Beckwith-Wiedemann syndrome
• Denys-Drash syndrome Denys-Drash syndrome
• Beckwith-Wiedemann syndrome enlargement of individual organs or body segments
• Connected w/ chronic congestion heart-failure cells (pulmonary), nutmeg liver (hepatic), cardiac cirrhosis
• elephantiasis Filariasis
• group of pathogens elicits cytopathic-cytoproliferative tissue viruses
• scleroderma excessive depositions of collagen
• Pulmonary infection, bulky &smelling feces, high sweat chloride levels, nutrient deficency? vitamin D
• Minamata disease Mercury poisoning
• Hyaline membrane disease can occur most likely among Infants born at less than 28 weeks of gestation
• Most common tumor of infancy Hemangioma
• most common germ cell tumor of infancy sacrococcygeal tumor
• Homer- Wright pseudorosettes Neuroblastoma
• Clinical Features in autosomal dominant disease Can Be Modified By Reduced Penetrance and variable expressivity. Some persons inherit the mutant gene but are phenotypically normal. This mode of expression is referred to as reduced penetrance Ex: manifestations of neurofibromatosis 1 range from brownish spots on skin to multiple tumors and skeletal deformities. • In many conditions, the age at onset is delayed, and symptoms and signs do not appear until adulthood (as in Huntington disease).
• (1) Expression of defect tends to be more uniform (2)Complete penetrance is common (3) Onset is frequently early in life. (4) autosomal recessive disorders
• high-arched palate & hyperextensibility of joints e.g. in Marfan is known as arachnodactyly
• They represent primary errors of morphogenesis. Intrinsically abnormal developmental process. Malformations usually are multifactorial, rather than the result of a single gene or chromosomal defect. Most common one is cleft-lip.
• They result from secondary destruction of an organ or body region that was previously normal in development. disruptions arise from an extrinsic disturbance in morphogenesis. Classic ex: Amniotic bands, denoting rupture of amnion with resultant formation of “bands” that encircle, compress, or attach to parts of the developing fetus. Not heritable & not assoc. w/ risk of recurrence in next pregnancy.
• They represent an extrinsic disturbance of development rather than an intrinsic error of morphogenesis. Fundamental to the pathogenesis of deformations is localized or generalized compression of the growing fetus by abnormal biomechanical forces, leading eventually to a variety of structural abnormalities. Most common cause is uterine constraint.
• This refers to multiple congenital anomalies that result from secondary effects of a single localized aberration in organogenesis. This is sequence and it includes Ex: oligohydramnios (or Potter) sequence. Oligohydramnios, denoting decreased amniotic fluid and renal agenesis.
• Malformation syndrome most often arise from a single causative condition (e.g., viral infection or a specific chromosomal abnormality) that simultaneously affects several tissues.
• Atresia describes the absence of an opening, usually of a hollow visceral organ or duct such as intestines and bile ducts.
• flattened nose, long philtrum, low placed ears, long forehead is associated with fetal alcohol syndrome
• babies born to mothers who smoke often have a low birth weight and may be prone to the sudden infant death syndrome (SIDS)
• Reduction in the incidence of neural tube defects by periconceptional intake of folic acid in the diet
• prematurity is the second most common cause of neonatal mortality
• congenital anomalies is the most common cause of neonatal mortality
• The immaturity of organ systems in preterm infants makes them especially vulnerable to Respiratory distress syndrome (RDS) , Necrotizing enterocolitis (NEC), Sepsis, Intraventricular and germinal matrix hemorrhage and Long-term sequelae, including developmental delay.
• There are many causes of respiratory distress in the newborn, including excessive sedation of the mother , fetal head injury during delivery, aspiration of blood or amniotic fluid, and intrauterine hypoxia secondary to compression from coiling of the umbilical cord about the neck.
• The most common cause of RDS is formation of “membranes” in the peripheral air spaces observed in infants who succumb to this condition.
• microscopically normal cells or tissues that are present in abnormal locations. Examples are a pancreatic tissue “rest” found in the wall of the stomach or small intestine and a small mass of adrenal cells found in the kidney, lungs, ovaries, or elsewhere are Heterotopia Orchoristomarefersto
• Hamartoma refers to an excessive but focal overgrowth of cells and tissues native to the organ in which it occurs. Although the cellular elements are mature and identical to those found in the remainder of the organ, they do not reproduce the normal architecture of the surrounding tissue. can be thought of as the linkage between malformations and neoplasms.
• The organ systems involved most commonly by malignant neoplasms in infancy and childhood are the hematopoietic system, neural tissue & soft tissues.
• abnormal development is teratogenesis

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