Unit III Genetic/Developmental, Childhood, and Mental Health Diseases and Disorders 1

Genetic and Developmental Diseases and Disorders Chapter 19 Genetic and Developmental Diseases and Disorders 2

Anatomy and Physiology Cell nucleus 46 chromosomes – 23 pairs Somatic cells reproduce through mitosis Double then divide—produce identical cells Germ cells (sex cells) reproduce through meiosis—result in each cell carrying only half the number of chromosomes. Haploid cells carrying 23 chromosomes 3

Anatomy and Physiology Normal females Sex chromosome is Xxthe ovum undergoes meiosis and divides into two separate X chromosomes Normal male Sex chromosomes is o spearate chromosomes, one X and one Y, so the male can give an X or Y germ cells(sperm) undergo meiosis and divide into Male sperm can be X or Y – male determines sex of child Chromosomes can be visualized by karyotyping Sex chromosomes can be evaluated by buccal smear 4

X Y X bearing sperm Y bearing sperm X X XY XX

                                     How are Barr Bodies formed? Any cell with more than one X chromosome will exhibit (n – 1) Barr bodies during interphase.  Each excess X chromosome will form one Barr body. This means that 46,XX women will have cells that exhibit one Barr body, while the cells from a 46, XY male will not exhibit any Barr bodies sex chromosomes can be evaluated by a buccal smear

Anatomy and Physiology Female X germ cell is much larger than male Y cell and carries more genetic information Chromosomes are made of deoxyribonucleic acid (DNA) and in a specific order; each is called a gene Chromosomes (one from each parent) pair up during fertilization; these paired genes are alleles 7

This normal karyotype shows 23 pairs of chromosomes: Pairs 1-22 are autosomes (they do not determine sex) Pair 23 are the sex chromosomes (XX female, XY male)

X chromosome Has over 1,500 genes Most genes on the X chromosome do not have corresponding alleles on the Y chromosome Y chromosome Has only 231 protein-encoding genes Some genes are unique only to the Y chromosome The human male is hemizygous for X-linked traits because he only has one copy of each X chromosome gene Some recessive X-linked traits expressed in males include: Red-green colorblindness Hemophilia

Anatomy and Physiology Each gene in an allele can be dominant or recessive Homozygous – matched alleles such as BB or bb Heterozygous – unmatched alleles such as Bb Expression of a physical trait is called phenotype 11

50% chance unaffected carrier (cf allele inherited from either parent) + = wild type allele cf = cystic fibrosis allele Carrier parents For each child conceived 25% chance unaffected noncarrier 50% chance unaffected carrier (cf allele inherited from either parent) 25% chance affected

aabbcc AABBCC 0 1 2 3 4 5 6 Number of dominant alleles

AABB aabb

Anatomy and Physiology p.477 Abnormalities can be due to: Chromosomal disorder Genetic disorder Environmental factors Combination of above Individuals acquire abnormal genes in two ways: Mutation of gene during meiosis Passage of abnormal gene from parents (heredity) 15

Most if not all characteristics and disorders considered “inherited” actually reflect input from the environment as well as genes Polygenic traits Determined by more than one gene Examples include height, skin color, and eye color Blood type O without genotype ii. Due to homozygous recessive expression of another gene, therefore blood types A and B are not possible – called Bombay phenotype Multifactorial traits Traits molded by one or more genes plus environmental factors Examples include height and skin color Common diseases such as heart disease, diabetes mellitus, hypertension, and cancers are multifactorial

Deviations from the normal chromosome number of 46 produce syndromes because of the excess or deficit of genes Chromosome number abnormalities may involve single chromosomes or entire sets of chromosomes Euploid is a normal chromosome number

Anatomy and Physiology Genetic disorders are passed to offspring in four ways: Autosomal dominant Autosomal recessive Sex-linked dominant Sex-linked recessive 18

Anatomy and Physiology p. 480 Approximately 2% of newborns are born with congenital anomalies Causes: 60% unknown cause 20% genetic 10% chromosomal 10% environmental 19

Diagnostic Tests Fetal ultrasound Amniotic fluid Maternal blood Detects malformations Amniotic fluid Reveals genetic and chromosomal disorders Maternal blood Reveals abnormal fetal substances 20

MD sex linked generally passed from mother to son the affected muscles are unable to store needed protein. Malnourished muscle are unable to store needed protein. Malnourished muscle fibers die and are replaced with fat and connective tissue. These fibers are unable to function as muscle fibers.

Musculoskeletal Muscular dystrophy (MD)--- Genetic degeneration or weakening of muscles Duchenne’s MD Most common type Cause: Sex-linked disorder passes mother to son Symptoms: Onset between 2 and 5 years of age Waddling gait, toe walking, lordosis, Gower’s maneuver p. 481 Treatment: No cure—usually in w/c by age 9 . life expectancy late teens or early 20s Physical therapy, orthopedic devices, exercise helpful 22

Musculoskeletal p. 481 Congenital hip dislocation (CHD) Abnormal hip joint resulting in femoral head slipping out of normal position Cause: Improper positioning in uterus, maternal hormones Symptoms: Asymmetrical folds of affected thigh Difference in leg length Limited abduction – Ortolanti’s sign Treatment: Closed or surgical reduction of femoral head 23

Musculoskeletal Clubfoot Also known as talipes equinovarus Common congenital abnormality of foot Cause: Unknown—thought to be due to genetic factors or fetal positioning Symptoms: Foot or feet turn inward with toes pointed downward and heel drawn upward Treatment: Gradual straightening Cast Splints 24

Musculoskeletal p. 483 Osteogenesis imperfecta Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition Osteogenesis imperfecta Abnormally brittle bones leading to fractures Cause: Inherited gene mutation Symptoms: Frequent bone fractures Blue coloration of sclera of eyes Treatment: No cure Tendency for bones to fracture often disappears by adulthood 25

Neurologic Hydrocephalus Abnormal accumulation of cerebrospinal fluid in brain due to obstruction Cause: Congenital defect, infection, tumor Symptoms: Rapid enlargement of infant head and bulging eyes Tight scalp and prominent head veins Shrill, high-pitched cry Treatment: Surgical correction with shunt placement page 483 26

Neurologic Cerebral palsy Congenital bilateral paralysis Cause: Inadequate blood or oxygen supply to brain during fetal development, birthing process, or infancy Symptoms: Hyperactive reflexes and rapid muscle contraction Muscle weakness with scissors gait 27

Neurologic Cerebral palsy Treatment: No cure Physical and speech therapy Orthopedic cast, braces, and surgery Anticonvulsants Muscle relaxants No cure 28

Neurologic Spina bifida---------- 483-(484 look at image) Congenital disorder Opening in spinal column Cause: Unknown Risk factors include maternal radiation, virus, genetic factors Symptoms: Differ with form of disease Forms of spina bifida Spina bifida occulta Meningocele Myelomeningocele—most serious Treatment: Surgery 29

Neurologic p. 484-485 Huntington’s disease Genetic defect of chromosome 4 Cause: Genetic – if one parent has disorder, 50% chance in offspring Symptoms: Behavioral changes Unsteady gait Increasing dementia Treatment: No cure Medications reduce symptoms

Eventually, a person with Huntington's disease requires help with all activities of daily living and care. Late in the disease, he or she will likely be confined to a bed and unable to speak. However, he or she is generally able to understand language and has an awareness of family and friends. Common causes of death include: Pneumonia or other infections Injuries related to falls Complications related to the inability to swallow

Cardiovascular p. 485 Congenital heart defects Heart and related vessels are most common sites of congenital defects Defects can range from small to quite large Collectively, these malformations are called congenital heart defects

Cardiovascular Congenital heart defects (continued) Cause: Symptoms: Unknown, but genetic tendency is strongly suspected Symptoms: Vary from mild (asymptomatic) to extreme with cyanosis, breathing difficulty, and heart murmurs Diagnosis: Electrocardiogram Physical examination Treatment: Early diagnosis Surgery to correct the defect

Cardiovascular Congenital heart defects (continued) Atrial septal defect Opening between right and left atria Commonly due to foramen ovale not closing at birth Causes increased workload on right heart—blood from the left atria can go back through ovale to R atria to be pumped to lungs again—this repumping causes increased workload

Cont. Ventricular septal defect Most common heart defect—25% Hole between right and left Blood shunted from left to right Causes increased workload on right heart The ductus arteriosus like the foramen ovale, normally closes off shortly after birth. If the structure does not close, or remains patent, the condition is called patent ductus arteriosus

Cardiovascular Congenital heart defects (continued) Patent ductus arteriosus--—occurs twice as frequently in girls as boys Connection between pulmonary artery and aorta that does not close off after birth Blood shunts from aorta to pulmonary artery Causes increased workload on heart and pulmonary system Coarctation of aorta Stricture or narrowing of aorta Causes increased blood pressure proximal to narrowingally—lower blood pressure dist Causes increased workload on heart

Cardiovascular Congenital heart defects (continued) Tetralogy of Fallot page 487 One of the most serious of congenital defects Combination of four problems Pulmonary valve stenosis—opening too small Right ventricle hypertrophy—R ventricle enlarges due to increased effort of pushing blood through the stenotic pulmonary valve Ventricle septal defect—blood can flow bac into R ventricle when L ventricle contracts Abnormal placement of aorta--aorta opens OVER the ventricular septal defect 37

Tetralogy of Fallot Babies are truly blue babies Tetralogy of Fallot Babies are truly blue babies. Cyanosis increases with age, and clubbing of fingers and toes becomes evident. Older children will rest in a squatting position to breath easier. Other symptoms are growth retardation, severe dyspnea with exercise, and frequent respiratory infections.

Blood Sickle cell anemia Hemophilia Chronic hereditary form of anemia (discussed in detail in Chapter 7) Chronic hereditary form of anemia Predominantly affects black population Hemophilia X-linked hereditary disorder passed from mother to son 40

Digestive p. 488 Digestive disorders both genetic and developmental range from mild to severe Many are diagnosed at birth Some are incompatible with life and must be corrected immediately 41

Digestive Developmental malformations Maternal rubella Several developmental malformations occur in the digestive system Cause: Unknown Might be related to genetic tendencies Might be related to maternal risk factors Maternal rubella Poor maternal nutrition Smoking Alcoholism 42

Digestive Developmental malformations (continued) Meckel’s diverticulum Outpouching of diverticulum of the ileum—may be asymptomatic the entire life and only found on autopsy Esophageal atresia Abnormal esophagus (atresia—is the congenital absence or closure of a normal opening or lumen in the body and can occur in a variety of areas) Congenital diaphragmatic hernia A hole in the diaphragm—abdominal organs might herniate through this opening 43

Digestive Developmental malformations (continued) p. 489 Imperforate anus Failure of the anus to connect to the rectum—infant will not pass stool. Abdominal pain and cramping with vomiting. Must be surgical corrected Cleft lip—affects nursing, speech, increases respiratory and middle ear infections One or more splits in upper lip Affects boys more frequently than girls Treatment: Surgical repair 44

Digestive Developmental malformations (continued) Cleft palate—hard palate (roof of mouth) does not close More serious than cleft lip Involves roof of mouth Treatment: Surgical repair Again causes problems with feeding, speaking, increases respiratory infections and middle ear infections 45

Cleft Lip and Palate Photo courtesy Dr. Joseph Konzelman, School of Dentistry, Medical College of Georgia 46

Cleft Lip and Palate Photo courtesy Dr. Joseph Konzelman, School of Dentistry, Medical College of Georgia 47

Digestive Genetic digestive disorders p. 490 Pyloric stenosis Narrowing of lower end of stomach Common anomaly of digestive tract Symptoms: Projectile vomiting Treatment: Pylorotomy—incising and suturing the pyloric sphincter muscle. 48

Pyloric Stenosis 49

Digestive Genetic digestive disorders (continued) Hirschsprung’s disease—seen more often in boys and those with Downs syndrom Absence of nerves in segment of colon Usually sigmoid colon—there is no peristalsis in this area. Symptoms: Chronic constipation Abdominal distention—massive distention of the colon Treatment: Surgical removal of affected segment Temporary colostomy may be necessary to allow adequate healing of colon 50

Digestive Genetic digestive disorders (continued) Phenylketonuria (PKU) Genetic disorder involving faulty metabolism of protein phenylalanine Diagnosis by blood test 72 hours after birth Mandatory in United States Lack of treatment can result in mental disability 51

Untreated PKU

Hypospadias Chordee Epispadias Urinary all can lead to problems with elimination of urine and can lead to difficulty with intecourse Hypospadias Abnormal congenital opening of male urinary meatus on under surface of penis—it can be severe with locations midshaft or near the scrotum. It occurs in 1 in 250 boys Chordee Abnormal fibrous band of tissue—abnormal downward curvature Epispadias Abnormal congenital opening of male urinary meatus on upper surface of penis Cause of these conditions: Unknown Treatments: No treatment to surgical repair 54

Urinary Wilms’ tumor Most common solid tumor affecting children and infants Cause: Thought to be genetic Highly malignant Usually replaces one whole kidney Symptoms: Asymptomatic until large enough to feel in child’s stomach Treatment: Chemotherapy Surgery 55

Reproductive Cryptorchidism Turner’s syndrome Condition of undescended testes (discussed in Chapter 17) Turner’s syndrome Affects females; ovaries are abnormal or absent Cause: Chromosomal disorder Females have only one X chromosome Rather than two XX chromosomes Symptoms: Failure to develop normal secondary sex characteristics Treatment: Symptoms can be reduced with growth with hormones and estrogen therapy 56

Reproductive Klinefelter’s syndrome—affects 1 in 1000 Affects males; do not develop secondary sex characteristics Cause: Chromosomal disorder Affected males have extra X chromosome—so XXY Symptoms: Not diagnosed until puberty due to abnormal male sexual development Sterility, abnormally small penis and testes General appearance of a eunuch – tall, slender body and long legs Treatment: Testosterone treatment and psychological counseling 57

Other Developmental Disorders Autism Developmental disorder characterized by difficulty communicating and in forming relationships Cause: Unknown Symptoms: Blank facial expression Involved with self – inaccessible to others Treatment Behavioral therapy Depends on severity and symptoms present 58

Other Developmental Disorders Stuttering Also known as stammering Developmental speech disorder Cause: anxiety with addressing others Symptoms: Hesitancy of starting and finishing words Prolonged pauses between words Treatment: Behavior modification Positive reinforcement 59

Multisystem Diseases and Disorders p. 494 Cystic fibrosis Hereditary disorder that affect all exocrine glands Cause: Hereditary recessive disorder Symptoms: Affects all exocrine glands leading to viscous secretions Treatment: Postural drainage Chest-clapping Antibiotics Bronchodilators Expectorants Oxygen 60

Multisystem Diseases and Disorders Down syndrome—p. 494 Also called trisomy 21 – a condition of having 3 chromosomes instead of the normal 2 in the 21st position of the chromosome chain Symptoms: Mild to severe mental disability Flat nasal bridge Low-set ears Slanted eyes Epicanthus Thick, protruding tongue Abnormal extremities Organ defects Treatment: Highly individualized to maximize mental and physical abilities 61

Trauma Failure to thrive—p. 495 Lack of physical growth and development in infant or child Cause: Disturbance in mother–child relationship or failure to bond Symptoms: Weight loss or failure to gain weight Anorexia, vomiting, diarrhea Irritability Rag-doll limpness 62

Trauma Failure to thrive (continued) Symptoms: Treatment: Unresponsiveness to affection Avoidance of eye contact Stiffening when cuddled Treatment: Teaching of mothering and nurturing behaviors to mother/parents Promotion of self-esteem 63

Trauma Fetal alcohol syndrome A group of symptoms and birth defects in an infant born to a mother who consumed alcohol during pregnancy Symptoms: Varying degrees of mental disability Decreased physical development Irritability in infants Hyperactivity in older children Microcephaly Increased incidence of ventricular septal defects 64

Trauma Congenital rubella syndrome Transmission of rubella virus to unborn fetus Can cause spontaneous abortion or major birth defects The most common defects are: Microcephaly Learning disorders Deafness Abnormal growth Heart defects Ocular lesions Prevention: Immunization No pregnancy for 3 months after immunization 65

Rare Diseases Anencephaly Achondroplasia Tay-Sachs disease Absence of brain or cranial vault Not compatible with life Achondroplasia Decreased long bone growth leading to type of dwarfism—(what we think of as “little people” Tay-Sachs disease Genetic error in lipid metabolism resulting in accumulation of toxins in brain 66