Congenital and Genetic Disorders

Prenatal causes for cerebral palsy and treatment.

- Maternal rubella, maternal diabetes, toxemia. - Treatment: geared towards overcoming disability.

Trisomy 21 (Down Syndrome)

- 95% have an extra chromosome 21, - Overall incidence is 1 in every 700, - Closely related to age of mother, - In early child bearing years, 1/2000, after 40 years of age rises to 1/40.

X- Linked Recessive Disorders (p. 575)

- Allele carried on the X chromosome but not the Y chromosome, - Manifested in heterozygous males lacking the matching unaffected gene on the Y chromosome, - Heterozygous females are carriers, homozygous recessive females may be affected, - Inheritance may appear to "skip generations", - Examples: Duchenne muscular dystrophy, classic hemophilia

Osteogenesis Imperfecta

- Autosomal dominant and recessive forms exist, - 1 in 30,000 to 1 in 60,000.

Cerebral palsy (p. 366)

- Broad term used to describe motor disorders, - Resulting from developmental abnormalities, - Associated with a mutation in the AP4B1 gene which hinders the ability of the cell to properly transport molecules from the Golgi apparatus to the correct lysosome. - Also from perinatal or postnatal CNS trauma occuring before age 5, - CP is NOT a diagnosis, it is a classification for nonprogressive spasticity, ataxia, or involuntary movements. - Specific cases cannot be identified until age 2, - May be lagging motor development, - Use of only one limb but not others.

Multifactorial disorders (p. 574/576)

- Large number of disorders are of this type, - Polygenic: meaning it is caused by multiple genes, - Often have pattern of familial inheritance, - Environmental component.

Amniotic Band Syndrome

- Characterized by major abnormalities of craniofacial region, body wall, and limbs, - Fibrous bands of tissue originate from the amniotic sac to encircle and constrict certain feta areas disrupting growth, - Pathogenesis is unknown. - Possible mechanisms include: vascular disruption, mechanical disruption, genetic disruption, germ disk disruption.

Single-Gene Disorder (p.574)

- Classified by inheritance patterns: Recessive, dominant, X-linked recessive. - Single gene controls a specific function: e.g. color-blindness. - May have systemic effects: e.g. cystic fibrosis, Tay-Sachs, phenylketonuria (PKU).

Patent Ductus Arteriosus (p.252)

- Connection between pulmonary artery and aorta remains open, - frequent in premature births, - Diagnosed by pounding pulse, increases pulmonary closure sound, - Acyanotic, - Treatment: fluid restriction, drugs for closure, surgery.

Spina bifida (p.365)

- Defective closure of spinal column, - Right and left neural arch do not fuse to midline due to lack of folic acid, - Associated with mutation of the MTHFR gene which codes for an enzyme that processes folate into methionine. - Two forms: SB occulta & SB cystica.

Cystic Fibrosis

- Disease of exocrine glands, - Most common lethal genetic disease among people of European decent, - 1 in 2400 births.

Congenital Diseases

- Disease that is present at birth, - Cause approximately 10% of neonatal deaths, - Major anomaly usually present in 3-4% of newborns, - By age 5, 7.5% of all children manifest some sort of defect.

Developmental Disorders (p. 577)

- Exposure to drugs, chemicals, or radiation during child-bearing years, - TORCH: maternal infections that can result in anomalies found in routine prenatal screening tests, - Exposure to known teratogens in the first 2 months of development, - Impair organogenesis.

X-Linked Dominant Disorders (p.575)

- Heterozygous males and females affected, - Reduced penetrance in females ( reduced expression), - Fragile X syndrome is an example : Most common genetic cause of cognitive deficits. Effects are variable are related to the extent of mutation of the allele.

Autosomal Dominant Disorders (p.575)

- Inheritance of one allele causes disorder; only one parent needs to carry allele. - No carriers: unaffected persons don't transmit disorder, - Some conditions become evident later in life. Because of this, allele for a disorder may have been passed on to the next generation before diagnosis of disease in parent. This is termed "delayed lethal" genotype.

Osteogenesis Imperfecta: Signs and Symptoms

- Numerous fractures ( can even be caused by breathing), - Easily chipped teeth, - Bluish sclerae, - Fracture callus may be normal but remodeled bone is of poor quality.

Spina Bifida occulta (p.365)

- Only one or two vertebras fail to close, - No protrusion of meninges.

Ventricular Septal Defect (VSD) (p. 252)

- Opening in the septum that divides the ventricles, - Frequently heard as a loud, harsh murmur at lower-left sternal border, - Acyanotic shunt, - Mutation of the GATA4 (a transcriptional activator) Gene leads to the VSD but it can be caused by others, - Treatment: often closes by 1 year, can respond to anti-congestive drugs, some repaired surgically.

Transposition of great vessels ( p.253)

- Pulmonary artery arises from left ventricle, aorta arises from right ventricle, - Usually associated with patent foramen ovale, - Rubella (or other viral illnesses during pregnancy), maternal age over 40, or maternal diabetes are factors that can increase the risk of this condition, associated with GATA4 mutation, - Cyanotic.

Neural Tube Defects

- Some of the most serious defects develop during the first 2 months of gestation, - accurate in utero detection is possible through amniocentesis and ultrasonography, - Folic acid supplements (4mg/day) before and during pregnancy can significantly reduce chances - Lack of folic acid increases chances of neural tube defects.

Single-gene Disorders (p. 574)

- Trait controlled by one set of alleles, - Transmitted to subsequent generations.

Proteus Syndrome

- caused by mutation in AKT1 gene in which it becomes activated by phosphorylation and suppresses apoptosis (cell death). - Mutation occurs during embryonic growth, - Some cells have the mutation and others do not (mosaicism), - Involves atypical growth of bones and skin, - probable condition of Joseph Merrick (the elephant man).

Cystic Fibrosis: Pathophysiology

- disrupts chloride transport across plasma membrane. - affected gland fall into 3 categories: 1) obstructed by thick, mucus-like material in the lumen of the gland. 2) produce excess of normal secretions 3) normal but secrete excessive Na and Cl in sweat *they say to watch out for kissing a baby and it having a salty taste.

Trisomy 21: Signs and Symptoms

- microcephaly and brachycephaly are present, - eyes are slanted with epicanthic folds, - flattened nasal bridge, - tongue is large, furrowed, and lack central fissure, - life expectancy is 40-50 years.

Proteus Syndrome: Signs and Symptoms

- multiple hyperostoses of calvaria, facial bones, and mandible. - Hemihypertrophy: overgrowth of one side of the face, body, or limbs. - Tumors on sin surface may be present, resembling lymphangioma (composed of lymph vessels).

Proteus Syndrome: Treatment

- no known cure.

Inherited disorders may be due to:

- single gene expression, - chromosomal defect, - polygenic expression.

Congenital disorder incidence varies with:

- the individual effect, - geographic area / gene pool / environment, - cultural practices (such as diet), - certain ante- and perinatal problems.

Autosomal Recessive Disorder

-Both parents must pass on the allele for the disorder. Parents may be heterozygous and unaffected ; termed carrier. Parents may be homogenous and affected. - Male and female kids affected equally, - Homozygous recessive child has the disorder, - Heterozygous child shows no clinical signs of disease; carrier.

Teratogenic agents (p. 574)

Agents that cause damage or changes during embryonic or fetal development.

Spina Bifida cystica (p.365)

Cyst is produced that contains: - Meninges (meningocele) - Spinal cord/nerves (myelocele) - Both (Myelomeningocele) Most common in lower thoracic, lumbar, and/or sacral regions. If myelomeningocele, can cause paralysis of limbs and organs.

Cystic Fibrosis: Diagnosis and Treatment

DIAGNOSIS - Suggested by clinical and laboratory signs, - Confirmed by abnormally high Na and Cl levels in sweat. TREATMENT - no cure, - largely supportive, - life expectancy is 28 years.

Cystic Fibrosis: Etiology, Signs and Symptoms.

ETIOLOGY - Carried by autosomal recessive trait, - Mutation of the CTR gene disrupts chloride transport across plasma membrane. SIGNS AND SYMPTOMS - Meconium ileus is earliest sign (mucus in ileum; this will usually be the first BM), - caused by obstruction of the ileum by viscid meconium, - chronic cough and wheezing associated with recurrent or chronic pulmonary infection.

Osteogenesis Imperfecta: Etiology

ETIOLOGY - inherited and caused by defective collagen formation from mutation in the COLIAI and COLIAII genes (90% of cases), - impaired ability of collagen fibers to bond together results in lax, stretchable connective tissue with low integrity.

Cleft lip/palate

Etiology: - failure of palate or lip to unite, - 1 in 700 to 800 births, - Sometimes caused by mutation of HSX1 gene (homebox), - Cleft lip causes no functional impairment, - Can interfere with feeding and breathing (hard to differentiate b/w air and food in pharynx) Treatment: - surgical repair.

Multifactorial disease with examples (p.576)

Genetic influences combined with environmental factors. Examples: - Cleft palate, - Congenital hip dislocation, - Congenital heart disease, - Type 2 diabetes mellitus.

Chromosomal Disorders (p. 576)

Result of too many or too few chromosomes. -Down Syndrome Trisomy 21, May be due to non-dysjunction or translocation - Turner Syndrome XO Affects females, short stature, infertility - Klinefelter syndrom XXY Extra X chromosome is present, infertility.

Erythroblastosis Fetalis: Signs, Symptoms, Diagnosis, Treatment

SIGNS AND SYMPTOMS - ranges from mild anemia to jaundice to death, - Jaundice from high bilirubin, - Spleen and liver may be enlarged. (spleen is primary site for RBC destruction). DIAGNOSIS - Maternal history and blood typing of mother and father, - Coomb's test TREATMENT - intrauterine transfusion

Hydrocephalus signs and symptoms, treatment, & diagnosis.

Signs and Symptoms - Enlarged head from non-communicating, - Bulging fontanelles from communicating, - Often associated with projectile vomiting. Diagnosis - measure head, - ultrasound can determine size of ventricles. Treatment - surgery to add shunt (implant bypass to fix blockage & drain CSF).

What does TORCH stand for?

T - Toxoplasmosis, O - Others, : (syphilis, varicella-zoster, parovirus B19) R - Rubella, C - Cytomegalovirus, H - Herpes infection (2-3%).

Osteogenesis Imperfecta: Treatment

TREATMENT - directed towards preventing or controlling the symptoms, maximizing independent mobility, and developing optimal bone mass and muscle strength. - No effective treatment is known.

Incidence

The frequency of occurrence over a period of time in relation to the population in which it occurs.

Chromosomal anomalies (p.573)

Usually from an error during meiosis, when the DNA fragments are displaced or lost, thus altering genetic information. - Non-disjunction, - Translocation.

Erythroblastosis Fetalis and Etiology

characterized by excessive rates of RBC destruction ETIOLOGY - caused by incompatibility between maternal and fetal blood, - Mother is Rh- and fetus is Rh+. (mother's antibodies for incompatible blood type transfers across placenta and attaches to embryos blood cells), - Can also happen with different blood types but is usually subclinical, - Antibody crosses placenta.

Hydrocephalus and etiology

ventricular enlargement with excessive CSF. ETIOLOGY: - Communicating: failure in reabsorption of CSF. Usually caused by meningeal inflammation secondary to infection or blood in subarachnoid space. -Non-communicating: blockage most often in cerebral aqueduct but can occur almost anywhere.