Genetic and Congenital Disorders

Patent Ductus Arteriosus

-connection between pulmonary artery and aorta remains open -frequent in premature births -diagnosed by bounding pulse, increased pulmonary closure sound -Acyanotic

Cerebral Palsy-Diagnosis

-cranial MRI

Spina Bifida

-defective closure of spinal column, associated with a mutation of the MTHFR gene which codes for an enzyme that processes folate into methionine

Ataxia

-defective muscle coordination

Coomb's test

-detects antibodies that bind to individual's own RBC's

Cystic Fibrosis

-disease of exocrine glands -most common lethal genetic disease among people of European descent -1 in 2,400 births

Hydrocephalus- Signs and Symptoms

-enlarged head from non-communicating -bulging fontanelles from communicating -often associated with projectile vomiting

Autosomal Dominant Disorders

inheritance of one allele causes disorder; only one parent needs to carry allele

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 childbearing years is 1/2000 after 40 yrs rises to 1/40

Recessive

-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"

Termed "delayed lethal" genotype

-Allele for disorder may have been passed on to the next generation before diagnosis of disease in parent -some conditions become evident later in life

Single-Gene Disorders

-Classified by inheritance patterns, ex. recessive, dominant, X-linked recessive -Single gene controls a specific function, ex. color-blindness -May have systemic effects, ex. cystic fibrosis

Multifactorial Disorders- Examples

-Cleft palate -Congenital hip dislocation -Congenital heart disease -Type II diabates mellitus

Hydrocephalus-Etiology

-Communicating= failure in reabsoprtion of CSF -Usually caused by meningeal inflammation secondary to infection or blood in subarachnoid -Non-communicating= blockage most often in cerebral aqueduct but can occur almost anywhere

SB Cystica

-Cyst produced that can contain: 1. Meninges (meningocele) 2. Spinal Cord (myelocele) 3. Both (myelomeningocele) -most common in lower thoracic, lumbar, and/ or sacral regions -can cause paralysis of limbs and organs

Ex. of Recessive Disorders

-Duchenne muscular dystrophy -Classic hemophilia

Multifactorial Disorders

-Genetic influences combined with environmental factors

Dominant

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

X-linked Disorders

-Recessive -Dominant

Chromosomal Disorders

-Trisomy 21(Down Syndrome)- may be due to non-disjunction or translocation -Turner Syndrome XO- affects females, short stature, infertility -Klinefelter Syndrome XXY- extra X chromosome is present, infertility

Teratogenic Agents

-agents that cause damage during embryonic or fetal development -exposure to drugs, chemical or radiation during child-bearing years -TORCH: maternal infections that can result in anomalities

Osteogenesis Imperfecta

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

Cerebral Palsy

-borad term used to describe a group of syndromes that include motor disorders -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 -It is a classification for children with nonprogressive spasticity, ataxia, involuntary movements

Cystic Fibrosis-Etiology

-carried by autosomal recessive trait -mutation of the CFTR gene disrupts chloride transport across plasma membrane

Proteus Syndrome

-caused by a mutation in AKT1 gene in which it becomes activated by phosphorylation and suppresses apoptosis -mutations occur during embryonic growth -some daughter cells have the mutation and others don't -involves atypical growth of bones and skin -probable condition of Joseph Merrick (the elephant man)

Erythroblastosis Fetalis-Etiology

-caused by incompatibility between maternal and fetal blood -mother is RH- and fetus is RH+ -can also happen with different blood types but is usually subclinical -antibody crosses placenta

Erythroblastosis Fetalis

-characterized by excessive rates of RBC destruction

Transposition of Great Vessels-Diagnosis

-chest x-ray, echocardiography

Cleft lip/palate- Etiology

-failure of palate or lip to unite -1 in 700 to 800 births -Cleft lip causes no functional impairment -Cleft palate can interfere with feeding and speech -sometimes caused by mutation of HSX1 gene (homeobox)

Patent Ductus Arteriosus-Treatment

-fluid restriction, drugs for closure, surgery

Cerebral Palsy-Treatment

-geared toward overcoming disability

Disorders present at birth:

-includes inherited or developmental disorders -a major anomaly is usually present in 3-4% of newborns

Osteogenesis Imperfecta- 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

Erythroblastosis Fetalis- Treatment

-intrauterine transfusion

Erythroblastosis Fetalis- Diagnosis

-maternal history and blood typing of mother and father -Coomb's test

Cerebral Palsy Prenatal Causes include:

-maternal rubella, maternal diabetes, toxemia -specific cases cannot be identified until age 2 -maybe lagging motor development -use of only one limb but not others

Hydrocephalus-Diagnosis

-measure head, ultrasonography can determine size of ventricles

Cystic Fibrosis-Signs and Symptoms

-meconium ileus is earliest sign -casued by obstruction of ileum by viscid meconium -chronic cough and wheezing associated with recurrent or chronic pulmonary infection

Trisomy 21 (Down Syndrome) 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 yrs.

Proteus Syndrome-Signs and Symptoms

-multiple hyperostoses of calvaria, facial bones, and mandible -Hemihypertrophy -tumors on skin surface may be present -resembling lymphangioma(composed of lymph vessels)

Cystic Fibrosis-Treatment

-no cure -largely supportive, bronchodilators, aerosol drugs to thin secretions -life expectancy is 37 yrs

Osteogenesis Imperfecta-Treatment

-no effective treatment known -directed toward preventing or controlling the symptoms, maximizing independent mobility and developing optimal bone mass and muscle strength

Proteus Syndrome- Treatment

-no known cure

Osteogenesis Imperfecta-Signs and Symptoms

-numerous fractures -easily chipped teeth -bluish sclerae -fracture callus may be normal but remodeled bone is poor quality

Ventricular Septal Defect- Treatment

-often closes by 1 yr, can respond to anticongestive drugs, some repaired surgically

Multifactorial Disorders

-often have pattern of familial inheritance -environmental component

SB Occulta

-only one or two verts fail to close, no protrusion of meninges

Hemihypertrophy

-overgrowth of one side of the face, body or limbs

Ventricular Septal Defect

-part of a number of conditions grouped as CCHD(critical congenital heart disease) -opening in spetum that divides ventricles -frequently heard as a loud, harsh murmur at lower-left sternal border -Acyanotic -Mutation of the GATA4 gene leads to VSD but it can be caused by others

Transposition of Great Vessels

-pulmonary artery arises from left ventricle, aorta arises from right ventricle -usually associated with patent foramen ovale -Although some factors, such as rubella or other viral illnesses during pregnancy, maternal age over 40, or maternal diabetes, may increase the risk of this condition, in most cases the cause is unknown.

Erythroblastosis Fetalis- Signs and Symptoms

-ranges from mild anemia to jaundice to death -jaundice from high bilirubin -spleen and liver may be enlarged

Transposition of Great Vessels- Signs and Symptoms

-severe cyanosis, metabolic acidosis, possible tachypnea, tachycardia during first 3-6 weeks of life

Mosaicism

-some daughter cells have the mutation and others don't

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

Cystic Fibrosis-Diagnosis

-suggested by clinical and laboratory signs -confirmed by abnormally high NA and Cl levels in sweat

Transposition of Great Vessels-Treatment

-surgery

Hydrocephalus-Treatment

-surgery to add shunt

Cleft Lip/Palate- Treatment

-surgically repair

Single-gene disorder

-trait controlled by one set of alleles -transmitted to subsequent generations

No carriers

-unaffected persons do not transmit the disorder

Chromosomal anomalies

-usually from an error during meiosis -non-disjunction -translocation

Hydrocephalus

-ventricular enlargement with excessive CSF

Autosomal Recessive Disorders

1. Both parents must pass on the allele for disorder 4. Male and female children are affected equally

Spina Bifida: Two Forms

1. SB occulta 2. SB cystica

Cystic Fibrosis-Patho

Affected glands fall into 3 categories: 1. obstructed by thick, mucus-like material in the lumen of the gland 2. produce an excess of normal secretions 3. normal but secrete excessive Na and Cl in sweat

Homozygous

Parents may be ______ and affected Recessive child has the disorder Both parents have to pass of the defective gene

Heterozygous

Parents may be _______ and unaffected Termed carriers One normal gene and one disease gene are present in the pair No clinical signs of the disease Child is the carrier