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Genetics

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Title: Genetics


1
Genetics
  • Genie Dorman, PhD, APRN, FNP-BC
  • Summer, 2010

2
Genetics Definitions
  • Genetics refers to the actions and inheritance
    of single genes a more accurate term when
    talking about genes within the human organism is
    genomics
  • Genome entire DNA within a given organism (this
    is called the organisms genotype)

3
Definitions - Continued
  • Human Genome Project (HGP)
  • International, collaborative research program
    whose goal was the complete mapping, sequencing,
    and understanding of all the genes of members of
    our species, Homo sapiens. Completed in April
    2003, the HGP gave us the ability to, for the
    first time, to read nature's complete genetic
    blueprint for building a human being.

4
Definitions - Continued
  • Human Genome - consists of 21,000 genes more
    than 99 is identical from person to person but
    in every 100 to 500 pairs there is a variation
  • Genotype the genome of an organism is its
    genotype

5
Definitions - Continued
  • Phenotype the observed trait seen on physical
    assessment or biochemical analysis (phenotype
    does not always match the genotype)
  • Karyotype - the chromosomal complement of an
    individual, including the number of chromosomes
    and any abnormalities. The term is also used to
    refer to a photograph of an individual's
    chromosomes.

6
Genetic Disorders
  • Genetic disorders are individually rare but
    common in the aggregate. Genetic disorders
    account for over 60 of early miscarriages and
    are the underlying cause of most developmental
    delays.

7
Genetic Disorders Classifiactions
  • Chromosomal 7 of all anomalies characterized
    by retardation of growth, retardation of
    development, structural defects (includes Trisomy
    18 (Edwards Syndrome) Trisomy 21 (Down
    Syndrome) Trisomy 13 (Patau Sydrome)
    Cri-du-Chat Turner Syndrome Klinefelter
    Syndrome

8
Genetic Disorders Classifiactions (cont.)
  • Single Gene Disorder demonstrating a Mendelian
    inheritance pattern accounting for another 7 of
    anomalies
  • 1. Autosomal dominant (AD)- Marfan Snydrome
  • 2. Autosomal recessive (AR)- Sickle Cell
  • 3. X-linked recessive (XLR)- Hemophilia

9
Genetic Disorders Classifiactions (cont.)
10
Genetic Disorders Classifiactions (cont.)
  • Single Gene Disorders (cont.)
  • Significant recurrence risk
  • Autosomal dominant conditions up
  • to 50 recurrence rates
  • Autosomal recessive and X-linked
  • recessive conditions up to 25
  • recurrence rates

11
Genetic Disorders Classifiactions (cont.)
  • Multifactorially Inherited Disorders-
  • account for 20 and results from an interplay
    of genetic and environmental factors (diabetes
    mellitus, schizophrenia)
  • Low recurrence risk (2 - 5 in primary relatives

12
Genetic Information and Nondiscrimination Act
  • Passed by Congress and became a Federal law May
    2008
  • Prohibits denying or altering coverage based on
    genetic information (providers cannot request,
    require, or purchase the results of genetic
    testing or disclose genetic information)

13
Genetic Information and Nondiscrimination Act
(cont.)
  • Prohibits employers from making hiring decisions
    or any conditions of employment based genetic
    information employers also cannot request,
    require, or purchase the results of genetic
    testing or disclose genetic information

14
Overview of Genetic Disorders
  • Trisomy 18 (Edwards Syndrome)
  • Trisomy 21 (Down Syndrome DS)
  • Fragile X Syndrome
  • Turners Syndrome
  • Klinefelter Syndrome
  • Tay-Sachs Disease
  • Marfan Syndrome
  • Hurler Sydrome
  • Prader-Willi Syndrome

15
  • Trisomy 18
  • (Edwards Syndrome)

16
Trisomy 18 Definition
  • Autosomal chromosomal disorder, trisomy of
    chromosome 18 associated with severe mental
    retardation and other congenital defects lt10
    survive until 1st birthday

17
Trisomy 18 Etiology/ Incidence
  • Nondisjunction during meiotic division resulting
    in trisomy of chromosome 18
  • Second most common autosomal chromosome disorder
  • 13500 to 8000 live births 31 female
    predominance
  • lt10 survive until 1st birthday

18
Trisomy 18 Signs and Symptoms
  • Small for gestational age
  • Hypertonia
  • Feeding problems/ growth failure
  • Severe global developmental delays

19
Trisomy 18 Physical Findings
  • Apnea
  • Microcephaly
  • Low set ears
  • Heart murmur
  • Unusual hand posture (clenched hands with
    over-riding fingers and crossed thumb)
  • Severe failure to thrive (FTT)

20
Trisomy 18
21
Trisomy 18
22
Trisomy 18 Diagnostic Tests/ Findings
  • Karyotype
  • Fluorescent in-situ hybridization (FISH) analysis
  • Results usually available within 48 hours
  • Echocardiogram to detect congenital cardiac
    defects

23
Trisomy 18 Management/ Treatment
  • Genetic counseling (Chorionic villi sampling or
    amniocentesis with subsequent pregnancies)
  • Psychological support to parents and family
  • Refer to cardiology
  • Support nutritional needs may require gastric
    feedings

24
Trisomy 18 Management/ Treatment (cont.)
  • Enroll in early intervention program for
    habilitative therapies
  • Assist family with management of special needs
    child- may require in-home nursing

25
Trisomy 18 Differential Diagnosis
  • Trisomy 13 (Patau Syndrome)
  • Cri-du-Chat (Cat-Cry Syndrome)

26
Trisomy 21 Down Syndrome (DS)
27
Down Syndrome Definition
  • A recognizable grouping of congenital physical
    malformation, coupled with mental retardation and
    karyotype 47 XY or XX 21 also known as Trisomy
    21

28
DS Etiology/ Incidence
  • Presence of critical lower region of a third 21
    chromosome, usually contributed due to
    nondisjunction in maternal zygote formation
  • 1700 births
  • Affects males and females equally
  • Increased risk with advanced maternal age, though
    most infants with DS (75) are born to younger
    mothers (lt35) due to higher birth rates among
    younger women

29
DS Signs and Symptoms
  • Mental Retardation, mild to severe
  • Typical phenotypic signs at birth
  • - Flattened, hypoplastic mid-face
  • - Small mouth with high, narrow palate
  • - Tongue large for mouth
  • - Small ears

30
DS Signs and Symptoms (cont.)
  • - Upward slanting palperbal fissures
  • - Hypotonia
  • - Inner epicanthal folds
  • - Sometimes brachydactyly shortening of hands
    and fingers (5th finger), single transverse
    palmar crease (50)

31
DS Signs and Symptoms (cont.)
  • - Penis appears small
  • - Flattened occiputic
  • - History of seizures- up to 13

32
Down Syndrome
33
Down Syndrome
34
DS Differential Diagnosis
  • Other genetic or chromosomal syndromes

35
DS Physical Findings
  • Phenotype as above
  • Signs of congenital heart disease- 50, e.g.,
    murmur abnormal heart rate, rapid respiratory
    rate, labored respirations, cyanosis
  • Signs of hypothyroidism and other endocrine
    problems - 15

36
DS Physical Findings
  • Signs of esophageal or duodenal atresia - 12
  • Ligamentous laxity - 100
  • Vision or hearing impairments - up to 90
  • Obesity - 50 by early childhood

37
DS Diagnostic Tests/ Findings
  • Pre or postnatal chromosome analysis reveals 47
    XY or XX 21 karyotype
  • CBC with differential to identify those with
    leukemia 10 to 15 fold increased risk
  • Radiographic finding of cervical instability - 10

38
DS Diagnostic Tests/ Findings
39
DS Management/ Treatment
  • Early intervention by PT, OT, speech therapists
  • Primary prevention via education re risk
    factors secondary prevention vie prenatal
    diagnosis
  • Genetic counseling for parents and older siblings
  • Periodic full history and physical with sensory
    and developmental evaluations

40
DS Management/ Treatment (cont.)
  • Nutritional Support
  • Prophylactic antibiotics to prevent SBE, if
    cardiac effects
  • Prompt consultation and referral for specialist
    treatment of associated conditions

41
Fragile X Syndrome
42
Fragile X Syndrome Definition
  • Nonrandom association of clinical signs and
    symptoms including recognizable phenotype of
    subtle physical abnormalities, mental retardation
    of varying degrees, behavioral abnormalities, and
    karyotype showing fragile site on X chromosome

43
Fragile X Syndrome Etiology/Incidence
  • Genetic anomaly, labeled FMR1, on X chromosome,
    the same position as the fragile site
  • Atypical X-linked recessive inheritance pattern
  • Affected individuals- 11000 males 12000 to
    12500 females

44
Fragile X Syndrome Etiology/Incidence (cont.)
  • Carrier females 1700
  • Approximately 20 of males asymptomatic, but can
    transmit gene resulting in symptomatic offspring
  • Most common inherited cause of mental
    retardation (MR) second most genetic cause of MR

45
Fragile X Syndrome Signs and Symptoms
  • Developmental Delay
  • Hyperactivity
  • Speech delay perservative speech echolalia
  • Poor gross motor coordination

46
Fragile X Syndrome Signs and Symptoms (cont.)
  • Stereotypes, e.g. talking to self, spinning, hand
    flappping
  • Gaze aversion
  • History of seizures - 17 to 50

47
Fragile X Syndrome Differential Diagnosis
  • Autism, Asperger syndrome, or pervasive
    developmental disorder
  • Mental retardation with nonspecific etiology
  • Klienfelter syndrome, Sotos syndrome
  • Attention deficit hyperactivity disorder

48
Fragile X Syndrome Physical Findings
  • Macrocephaly
  • Prominent forehead with long face and prominent
    jaw, especially in adolescence
  • Macro-orchidism in adolescent males may be seen
    as early as age 5
  • Protuberant, large ears, long or wide

49
Fragile X Syndrome Physical Findings (cont,)
  • Soft, smooth skin
  • Heart murmur or apical midsystolic click
  • Otitis media with effusion
  • Strabismus - 40
  • Joint laxity (especially fingers), hip
    subluxation, occasionally club foot

50
Fragile X Syndrome
51
Fragile X Syndrome Diagnostic Tests/ Findings
  • DNA analysis from whole blood in approved
    labrotory to confirm diagnosis
  • Prenatal testing from chorionic villus or
    amniocentesis sample

52
Fragile X Syndrome Management/Treatment
  • Psychosocial support to parents, child and family
  • Genetic counseling - no spontaneous mutations
    have been found for Fragile X syndrome all
    family members should undergo genetic testing to
    identify transmitting male, carrier females, and
    affected individuals

53
Fragile X Syndrome Management/Treatment (cont.)
  • Regular well-child examinations with attention
    to
  • Cardiac auscultation - if click or murmur heard,
    obtain echocardiogram, consider referrral to
    cardiologist for possible mitral valve prolapse
  • Otoscopic evaluation - serous otitis media

54
Fragile X Syndrome Management/Treatment (cont.)
  • Ophthalmologic evaluation - strabismus (40),
    myopia
  • Developmental evaluation - mild to severe delays,
    (usually moderate)
  • Anticipatory guidance

55
Fragile X Syndrome Management/Treatment (cont.)
  • Enroll in early intervention as soon as delays
    are recognized speech/ language therapy and
    sensory/ motor integration therapy thought to be
    most helpful
  • Ensure appropriate educational placement with
    necessary supports
  • Prophylactic antibiotics with dental care and all
    surgeries for SBE, mitral valve prolapse

56
Turner Syndrome
57
Turner Syndrome Definition
  • Chromosomal anomaly resulting in 45,X0 (female)
    karyotype, with predictable associated signs and
    symptoms

58
Turner Syndrome Etiology/ Incidence
  • Nondisjunction during meiotic division, usually
    maternal more than half have a mosaic
    chromosomal complement (45,XO/46/XX)
  • 11500 to 12500 live births most common
    sex-chromosome anomaly affecting females many
    affected embryos do not survive to term

59
Turner Syndrome Signs and Symptoms
  • Short stature with "square" appearance
  • Low hairline
  • Chronic ear infection
  • Learning disabilities
  • Lack of development of secondary sexual
    characteristics

60
Turner Syndrome Differential Diagnosis
  • Congenital lymphedema without Turner's karyotype
  • Coarctation of aorta without Turner's karyotype

61
Turner Syndrome Physical Findings
  • Neonatal - lymphedema, webbed neck, low hairline,
    swelling of hands and feet
  • Widely spaced, often inverted nipples with
    "shield" shaped chest
  • Heart murmur
  • Ear deformities

62
Turner Syndrome Physical Findings (cont.)
  • Scoliosis (10)
  • Nail dysplasia
  • Defective dentition
  • High blood pressure
  • Strabismus, amblyopia, ptosis

63
Turner Syndrome
64
Turner Syndrome Diagnostic Tests/Findings
  • Cardiac ultrasonography or MRI for
  • Coarctation or aorta (20)
  • Bicuspid aortic valve (50)
  • Renal ultrasound to detect renal anomalies
  • Cytogentic testing for Karyotype 45 XO

65
Turner Syndrome Diagnostic Tests/Findings
  • Thyroid function to detect low T4, high TSH
    indicating hypothyroidism
  • Abdominal and pelvic ultrasound to detect gonadal
    dysgenesis
  • Plasma gonadotropin studies to detect low levels
    of normal female hormones
  • Renal ultrasound to detect renal anomalies

66
Turner Syndrome Management/Treatment
  • Refer to endocrinology
  • Growth hormone therapy beginning when growth
    falls below 5th percentile on normal female child
    growth chart
  • Hormone (estrogen) replacement therapy beginning
    about 14 years of age
  • Monitor for hypothyroidism

67
Turner Syndrome Management/Treatment (cont.)
  • Genetic counseling
  • Psychosocial support
  • Assistance in school for learning disabilities
  • Referral to cardiology for cardiac anomaly
    diagnosis and treatment

68
Turner Syndrome Management/Treatment (cont.)
  • Referral to ENT, orthopedic, urology,
    ophthalmology, pediatric dentist as needed
  • Prophylactic antibiotics for SBE if cardiac
    effects present

69
Klinefelter Syndrome
70
Klinefelter Syndrome Definition
  • Nonrandom association of physical
    characteristics and learning and behavioral
    disorders seen in males with the 47,XXY karyotype

71
Klinefelter Syndrome Etiology/Incidence
  • Maternal meiotic nondisjunction resulting in
    contribution of two X chromosomes to maternal
    zygote (ova) when ova is fertilized by sperm
    containing one Y chromosome, resulting embryo has
    Klinefelter karyotype

72
Klinefelter Syndrome Etiology/ Incidence (cont.)
  • 11000 live births
  • Most common cause of hypogonadism and infertility
    in men

73
Klinefelter Syndrome Signs and Symptoms
  • Tall male, especially at adolescence and beyond
  • Slow, incomplete pubertal development
  • Behavioral and psychiatric disorders (shy,
    immature, anxious, aggressive, antisocial)

74
Klinefelter Syndrome Signs and Symptoms (cont.)
  • Thin child
  • Language impairment

75
Klinefelter Syndrome Differential Diagnosis
  • Marfan syndrome
  • Sotos syndrome
  • Trisomy 8p

76
Klinefelter Syndrome Physical Findings
  • Tall for age, with disproportionate lower limb
    length
  • Gynecomastia
  • Small, firm testes
  • Cryptorchidism
  • Small phallus
  • Hypospadias

77
Klinefelter Syndrome
78
Klinefelter Syndrome Diagnostic Tests/ Findings
  • Chromosome analysis yields 47, XXY karyotype
  • High FSH, LH and low testosterone levels

79
Klinefelter Syndrome Management/Treatment
  • Early intervention for learning disorders
  • Counseling/ therapy for behavioral disorders
  • Psychosocial support for family
  • Genetic counseling

80
Klinefelter Syndrome Management/Treatment (cont.)
  • Refer to endocrinology for consideration of
    testosterone therapy at age 11 or 12
  • Screen for breast cancer (4)
  • Reduction mammoplasty for severe gynecomastia

81
Tay-Sachs Disease
82
Tay-Sachs Disease Definition
  • Inborn error of metabolism resulting in
    neurologic degenerative disease and death,
    usually by 3 years of age

83
Tay-Sachs Disease Etiology/ Incidence
  • Autosomal recessive single gene disorder
    deficiency of hexosaminidase A (hex A) which is
    necessary for breakdown of ganglioside Gm2 as
    glycoside accumulates in neurons, axons
    degenerate and demyelination occurs

84
Tay-Sachs Disease Etiology/ Incidence (cont.)
  • 310,000 live births mainly in Ashkenazic Jewish
    population gene carrier frequency in U.S. 127
    among Jews and 1380 among non-Jews

85
Tay-Sachs Disease Signs and Symptoms
  • Normal development until age 3 to 6 months, then
    progressive deterioration
  • Listlessness
  • Muscle weakness
  • Slow neurological development, loss of
    developmental milestones

86
Tay-Sachs Disease Signs and Symptoms (cont.)
  • Frequent upper respiratory infections
  • Apathy, irritability
  • Seizures
  • Deafness/ Blindness
  • Feeding problems

87
Tay-Sachs Disease Physical Findings
  • Other inborn errors of metabolism
  • Leukodystrophies
  • Muscular dystrophy

88
Tay-Sachs Disease Diagnostic Tests/ Findings
  • Hypotonia, followed by spasticity and paralysis
  • "Cherry red" spot on retina
  • Translucent skin, delicate pink coloring
  • Abnormal increase in head size due to cerebral
    gliosis

89
Tay-Sachs Disease
90
Tay-Sachs Disease
91
Tay-Sachs Disease Diagnostic Tests/ Findings
(cont.)
  • Decerebrate posturing
  • Dysphasia
  • Eventual vegetative state
  • Serum enzymatic assay yields deficiency of
    hexosaminidase A

92
Tay-Sachs Disease Management/ Treatment
  • Genetic counseling
  • Primary prevention via carrier screening
  • Secondary prevention via prenatal diagnosis and
    elective termination of pregnancy

93
Tay-Sachs Disease Management/ Treatment (cont.)
  • No known treatment for underlying metabolic
    deficiency
  • Supportive/ comfort care for child assist to
    obtain home nursing services as disease
    progresses and care burden increases

94
Marfan Syndrome
95
Marfan Syndrome Definition
  • Inherited disorder of connective tissue affects
    the skeletal, cardiovascular and ocular systems

96
Marfan Syndrome Etiology/ Incidence
  • Autosomal dominant inheritance of defective
    fibrillin gene mapped to chromosome 15 15
    sporadic mutation
  • Incidence is 120,000

97
Marfan Syndrome Signs and Symptoms
  • Skeletal - tall stature long, thin extremities,
    long fingers, narrow facies
  • Rapid heart rate, chest pain, palpitations or
    syncope suggestive of mitral valve prolapse

98
Marfan Syndrome Signs and Symptoms (cont.)
  • Vision impairment
  • Normal intelligence with learning disorders,
    attention deficit hyperactivity disorder (40)

99
Marfan Syndrome
100
Marfan Syndrome
101
Marfan Syndrome Differential Diagnosis
  • Beals syndrome (congenital contracultural
    arachnodactyly)
  • Homocystinuria

102
Marfan Syndrome Physical Findings
  • Skeletel
  • - Loose joints
  • - Scoliosis (60)
  • - Pectus excavatum or carinatum
  • - Narrow Palate

103
Marfan Syndrome
104
Marfan Syndrome Physical Findings (cont.)
  • - Dolichomorphism - elongation of tubular bones,
    as evidenced by increased upper limb span, low
    upper to lower segment ratio, hand length
    exceeding 11 of height, foot length exceeding
    15 of height

105
Marfan Syndrome Physical Findings (cont.)
  • Murmur indicative of mitral valve prolapse
  • Ocular - upwardly dislocated lens, retinal
    detachment
  • Myopia

106
Marfan Syndrome Diagnostic Tests/Findings
  • Diagnosis based on clinical manifestations must
    document involvement of at least one of the three
    systems - cardiovascular, ocular, skeletal
  • Positive family history plus one or more systems
    (as above) conclusive

107
Marfan Syndrome Diagnostic Tests/Findings (cont.)
  • Cardiac evaluation (chest, radiograph,
    electrocardiogram, echocardiogram) - mitral valve
    prolapse common signs of dilatation of aortic
    root or dissecting aortic aneurysm
  • Ocular evaluation - slit-lamp examination
  • Skeletal evaluation - scoliosis screening trunk/
    extremities ratio

108
Marfan Syndrome Management/ Treatment
  • Refer to cardiology for periodic echocardiogram
    to detect dissecting aortic aneurysm, mitral
    valve prolapse in severe cases, surgical graft
    repair of the ascending aortic valve has been
    successful
  • Propanolol to reduce effect of ventricular
    ejection on ascending aorta

109
Marfan Syndrome Management/ Treatment (cont.)
  • Refer to ophthalmology for treatment of myopia,
    lens subluxation, cataracts, glaucoma, retinal
    detachment
  • Refer to endocrinology for hormonal treatment to
    curtail height, valuable psychological effect
    prevention of scoliosis and kyphosis prevention
    of secondary problems of feet

110
Marfan Syndrome Management/ Treatment (cont.)
  • Psychosocial support for patient and family
  • Genetic counseling
  • Ensure mainstream or inclusive school placement
    with any necessary supports and attention to
    limitations as related to cardiovascular
    involvement

111
Hurler Syndrome (MPS IH)
112
Hurler Syndrome Definition
  • Inborn mucopolysaccharidosis metabolic disorder
    in which dermatan and heparan sulfate accumulate
    and are excreted in urine typically death occurs
    by 10 years of age

113
Hurler Syndrome Etiology/ Incidence
  • Deficiency of enzyme a-L-iduronidase autosomal
    recessive inheritance
  • 1100,000

114
Hurler Syndrome Signs and Symptoms
  • Coarse facial features with enlarged tongue, full
    lips, flat nasal bridge mild at birth,
    progressing with growth
  • Developmental peak at age 2, followed by
    deterioration
  • Recurrent inguinal hernia

115
Hurler Syndrome
116
Hurler Syndrome
117
Hurler Syndrome Signs and Symptoms (cont.)
  • Vision and hearing impairments
  • Joint limitations and contractures
  • Short stature

118
Hurler Syndrome Differential Diagnosis
  • Other progressive neuropathies and inborn errors
    of metabolism, particularly other
    mucopolysaccharidoses and thyroid deficiency

119
Hurler Syndrome Physical Findings
  • Skeletal abnormalities, including spinal
    anomalies/ gibbus formation
  • Macrocephaly, scaphocephaly
  • Hepatosplenomegaly

120
Hurlers Syndrome
121
Hurler Syndrome Physical Findings (cont.)
  • Clouded corneas
  • Inguinal/ umbilical hernia
  • Valvular heart disease coronary artery disease

122
Hurler Syndrome Diagnostic Tests/ Findings
  • Prenatal diagnosis with amniocentesis or
    chorionic villus sampling and enzyme analysis
  • Postnatal via serum and urine enzyme analysis

123
Hurler Syndrome Management/ Treatment
  • Genetic counseling
  • Psychosocial counseling
  • Anticipatory guidance
  • Early intervention appropriate school placement
    with supports as needed

124
Hurler Syndrome Management/ Treatment (cont.)
  • Bone marrow transplantation in selected cases,
    especially after early diagnosis and human
    leukocyte antigen (HLA) matched sibling donor
  • Refer to audiology and ophthalmology for
    evaluation and treatment, as indicated

125
Hurler Syndrome Management/ Treatment (cont.)
  • To date, enzyme replacement therapy not effective

126
Prader-Willi Syndrome
127
Prader-Willi Syndrome - Definition
  • Congenital disorder characterized by voracious,
    uncontrollable apetite and obesity

128
Prader-Willi Syndrome Etiology/ Incidence
  • Usually sporadic mutation when detectable (about
    50) mutation at same location of chromosome 15
    as the mutation for Angleman syndrome, although
    conditions are very dissimilar due to phenomenon
    of genetic imprinting
  • 110,000 to 115,000 incidence

129
Prader-Willi Syndrome Signs and Symptoms
  • Voracious appetite during childhood and beyond,
    resulting in severe obesity
  • Mental retardation
  • Behavioral problems
  • Hypotonia, poor suck and feeding problems in
    infancy resolution with time

130
Prader-Willi Syndrome Differential Diagnosis
  • Other neurological and musculoskeletal disorders
    with early hypotonia (including cerebral palsy)
    and developmental delay

131
Prader-Willi Syndrome Physical Findings
  • Obesity
  • Small hands and feet
  • Small genitalia
  • Cryptorchidism
  • Short stature
  • Scoliosis

132
Prader-Willi Syndrome
133
Prader-Willi Syndrome
134
Prader-Willi Syndrome Diagnostic Tests/ Findings
  • In 50 of cases, chromosome analysis detects
    aberration of chromosome 15
  • Remainder of cases are diagnosed by clinical
    signs and symptoms

135
Prader-Willi Syndrome Diagnostic Tests/ Findings
(cont.)
  • Growth Hormone deficiency frequent, but not
    universal

136
Prader-Willi Syndrome Management/ Treatment
  • Behavioral therapy for control of eating and
    other problem behaviors
  • Genetic counseling
  • Early intervention and appropriate school
    placement with supports

137
Prader-Willi Syndrome Management/ Treatment
(cont.)
  • Psychosocial support for family and child
  • Refer to endocrinology for evaluation and
    management of Growth Hormone deficiency

138
Cerebral Palsy (CP)
139
Cerebral Palsy Definition
  • Disorders of motion and posture related to static
    injury to the developing brain
  • Types
  • Spastic(diplegia, tetraplegia, hemiplegia) most
    frequent
  • Dyskinetic
  • Ataxic
  • Mixed

140
Cerebral Palsy Etiology/ Incidence
  • CNS insult may be congenital, hypoxic, traumatic
    or ischemic may occur prenatally, perinatally,
    postnatally
  • Birth asphyxia associated with prematurity and
    very low birth weight
  • Apgar score of 3 or less at 20 minutes associated
    with 250 times increased risk

141
Cerebral Palsy
  • Prevalence 2.7 1000 at school entry most common
    pediatric physical disability
  • Tetraplegia associated with serious intrauterine
    infections, fetal encephalopathies and perinatal
    hypoxia
  • Hereditary spastic type CP - rare

142
Cerebral Palsy Signs and Symptoms
  • Movement or posture abnormality that evolves with
    growth, but is not itself progressive
  • Delays in reaching developmental milestones,
    especially motor

143
Cerebral Palsy
  • Infancy
  • Abnormal or retained primitive reflexes
  • Poor muscle tone in first few weeks
  • Some irritability, lethargy
  • Weak suck, difficulty swallowing
  • Oral hypersensitivity
  • Fisted hands, even at rest

144
Cerebral Palsy
  • Later infancy/ toddler
  • Scissoring
  • Toe to toe gait if ambulatory
  • "W" sitting
  • "Bottom Scoot" in place of crawl
  • Resistance to spoon feeding/ table foods
  • Tonic bite, tongue thrust
  • Early hand preference

145
Cerebral Palsy
  • Vision impairment (50)
  • Hearing impairment (10)
  • Seizures (35 to 50)
  • Mental retardation (50 to 75) more common with
    greater physical disability

146
Cerebral Palsy Differential Diagnosis
  • Neurodegenerative disorders such as Duchenne
    muscular dystrophy
  • Inborn errors of metabolism
  • Brain tumor
  • Hydrocephalus
  • Subdural hematoma
  • Dystonias

147
Cerebral Palsy Physical Findings
  • Abnormal muscle tone (hypo or hypertonia)
  • Infancy - retained primitive reflexes
  • Hyperactive tendon and heightened stretch
    reflexes positive Babinski
  • Restricted joint range of motion

148
Cerebral Palsy Physical Findings (cont.)
  • Hip click or clunk on Barlow maneuver or Ortolani
    test
  • Movement related muscle spasms
  • Low weight for height
  • Neuromuscular scoliosis

149
Cerebral Palsy Diagnostic Tests/ Findings
  • Developmental evaluation - delays in gross motor,
    fine motor, speech, according to type of CP and
    presence of mental retardation
  • Brain MRI - periventricular leukomalacia

150
Cerebral Palsy Management/Treatment
  • Coordinate interdisciplinary management to
    promote optimum health and function
  • Enroll in early intervention services

151
Cerebral Palsy Management/Treatment
  • Identify and treat associated conditions (e.g.,
    seizures, visual impairment, hearing impairment,
    gastroesophageal reflux)
  • Prevent secondary conditions (e.g., failure to
    thrive, skin breakdown, dental caries)

152
Cerebral Palsy Management/Treatment
  • Functional therapies to build on strengths and
    promote compensation for physical impairments
  • Parent/ family support for positive coping and
    stress relief

153
Cerebral Palsy Management/Treatment
  • Spasticity relief
  • Enternal medication - lioresal, diazepam,
    dantrium, sodium, tizanidine hydrochloride
  • Selective dorsal root rhizotomy

154
Cerebral Palsy Management/Treatment
  • Nutritional support
  • Ensure appropriate education with supportive
    services and therapies

155
Spina Bifida
156
Spina Bifida Definition
  • Congenital multisystem defect resulting from
    failure of neural tube closure during early
    embryonic development one of several "neural
    tube defects"

157
Spina Bifida
158
Spina Bifida Etiology/ Incidence
  • Multifactorial inheritance pattern environmental
    contribution not well understood, although
    addition of folic acid intake reduces occurrence
    probability by one-half
  • Myelomeningocele - 11000 decreasing, probably
    due to folic acid supplementation and prenatal
    diagnosis with selective termination (not proven)

159
Spina Bifida
  • 2007 CDC reports 3,000 babies in the US born
  • Spina bifida occulta - incidence up to 10 of
    population
  • 2007 CDC reports 18 of women 18-24 aware of
    folic acid

160
Spina Bifida Signs and Symptoms
  • Urinary "dribbling", unable to achieve urinary
    continence
  • Frequent urinary tract infections
  • Chronic constipation, difficulty with bowel
    continence

161
Spina Bifida Signs and Symptoms
  • Intelligence in normal range, but with learning
    disorders, often with attention deficit
    hyperactivity disorder
  • Motor developmental delays, especially lower
    extremity related gross motor delays

162
Spina Bifida Differential Diagnosis
  • Syndromes of which spina bifida is associated,
    e.g., Meckel-Gruber syndrome

163
Spina Bifida Physical Findings
  • Spina bifida occulta - usually benign may have
    sacral dimple, hairy patch at base of spine,
    uneven gluteal folds
  • Arnold-Chiari Type II CNS malformation (nearly
    100) - associated with progressive
    hydrocephalus, difficulty swallowing,
    hypoventilation, apnea

164
Spina Bifida Physical Findings (cont.)
  • Meningocele or Myelomeningocele - signs at birth
    include lesion at some point along
    thoraco-lumbar-sacral spine, often with cyst-like
    structure protruding neural elements may be
    apparently abscent or may be easily visualized
    within the sac
  • Widely spaced cranial strucures, bulging
    fontanel, macrocephaly (with hydrocephalus)

165
Spina Bifida Physical Findings (cont.)
  • Lack of typical lower extremity function,
    sometimes with orthopedic deformity (club foot,
    dislocated or sublaxed hip, tibial torsion)
  • Abnormal deep tendon reflexes in lower
    extremities

166
Spina Bifida Physical Findings (cont.)
  • Abnormal neonatal reflexes in lower extremities
  • Decreased or absent anal wink
  • Atrophied lower extremity/ hip muscles

167
Spina Bifida Physical Findings (cont.)
  • Scoliosis, kyphosis
  • Obesity in older children and adolescents (gt50)
  • Neurogenic bowel and bladder
  • Latex sensitivity (gt40)

168
Spina Bifida Diagnostic Tests/Findings
  • Prenatal diagnosis possible by maternal serum
    screening for elevated alpha-fetoprotien,
    followed by ultrasound diagnostics for spinal
    anomaly and heard "lemon sign
  • The lemon sign refers to the shape of the fetal
    skull at ultrasonography
  • (US) when the frontal bones lose their normal
  • convex contour and appear flattened or inwardly
    scalloped.
  • This gives the skull a shape similar to that of a
    lemon (Figs 1,
  • 2). The sign is seen on transverse sonograms of
    the fetal cranium
  • obtained at the level of the ventricles (1,2).
  • EXPLANATION
  • The lemon sign has a strong association with
    spina bifida. Although
  • the exact pathogenesis is unknown, it has been
    postulated
  • that the decrease in the intraspinal pressure in
    neonates with spina
  • bifida causes the brain to shift downward. This
    shift decreases the
  • intracranial pressure, which is reflected onto
    the fetal cranium

169
Spina Bifida Diagnostic Tests/Findings (cont.)
  • Postnatal diagnosis made on clinical basis
  • Hydrocephalus after birth, increasing head
    circumference out of proportion to other growth
    parameters

170
Spina Bifida Management/ Treatment
  • Infants diagnosed parentally should be referred
    to tertiary center with appropriate supports for
    birth (possible planned C-section) and immediate
    neonatal intensive care

171
Spina Bifida Management/ Treatment (cont.)
  • Refer to multidisciplinary treatment center for
    specialty management - assistance from
    orthopedists, urologists, neurosurgeon,
    developmental pediatrician, orthotist, physical
    and occupational therapists, nutritionist,
    advanced practice nurse and social worker

172
Spina Bifida Management/ Treatment (cont.)
  • Enroll infant in early intervention program as
    soon as medically stable
  • Monitor for urinary tract infections expect less
    common organisms

173
Spina Bifida Management/ Treatment (cont.)
  • Monitor development of orthopedic problems,
    especially scoliosis and unilateral hip
    subluxation or dislocation baseline and
    follow-up radiographic studies

174
Spina Bifida Management/ Treatment (cont.)
  • Monitor for shunt malfunction if presence of
    shunted hydrocephalus baseline head CT scan
    follow-up if increased intracranial pressure
    suspected refer to neurosurgeon for evaluation
    of suspected shunt malfunction or tethered card

175
Spina Bifida Management/ Treatment (cont.)
  • Monitor for skin breakdown
  • Nutritional and behavioral intervention to
    prevent obesity
  • Test for latex sensitivity (skin or RAST) latex
    precautions

176
Spina Bifida Management/ Treatment (cont.)
  • Anticipatory guidance for development, safety
  • Psychosocial support to family and child
  • Assistance finding least restrictive school
    placement and other community supports - restrict
    from heavy contact sports only otherwise full
    inclusion should be encouraged

177
Spina Bifida Management/ Treatment (cont.)
  • Genetic counseling
  • All women of child bearing age should consume 0.4
    mg folic acid daily to help prevent neural tube
    defects women at high risk should consult
    obstetrician for higher dose, 4.0 mg/day
    recommended

178
Sudden Infant Death Syndrome (SIDS)
179
Sudden Infant Death Syndrome Definition
  • "The sudden death of an infant under 1 year of
    age that remains unexplained after a thorough
    case investigation, including performance of a
    complete autopsy, examination of the death scene,
    and review of the clinical history" (Brooks,
    1997, p. 1622)

180
Sudden Infant Death Syndrome Etiology/ Incidence
  • Unknown cause to date
  • In 1996 was 76.5 per 100,000 in the US
  • In 2004 was 56 per 100,000 which was 8.1 of all
    infant death in the US
  • Peak incidence 2 to 4 months uncommon before 2
    weeks and after 6 months

181
Sudden Infant Death Syndrome Signs and Symptoms
  • Infant unexpectedly found lifeless after a period
    of sleep

182
Sudden Infant Death Syndrome Differential
Diagnosis
  • Meningitis
  • Intracranial hemorrhage
  • Myocarditis
  • Accidental trauma
  • Child abuse

183
Sudden Infant Death (cont.)
  • Avoid heavy blankets, over bundling
  • Apnea monitoring for high risk infants
  • Premature with persistent apnea
  • Infant born after one previous siblings with SIDS
  • Post-apparent life threatening event (ALTE)
    requiring stimulation
  • Infants with central hypoventilation syndrome

184
Sudden Infant Death Syndrome Physical Findings
  • Full cardiorespiratory arrest
  • Unresponsive to resuscitation

185
Sudden Infant Death Syndrome Diagnostic Tests/
Findings
  • Diagnosis of exclusion, with autopsy and
    investigation failure to find adequate cause of
    death

186
SIDS Management/Tx
  • Risk reduction
  • Promote excellent prenatal care
  • Supine or side sleeping position for normal
    healthy infants
  • Avoid maternal and passive smoking
  • Separate sleeping place for infants
  • Avoid soft bedding
  • Maintain comfortable room temperature

187
SIDS Management/Tx
  • After infants death
  • Maximum support for family, others
  • Provide factual information
  • Assist with necessary tasks
  • Assist nursing mother with abrupt cessation of
    breast feeding

188
February 4, 2010 A new study confirms that
infants who die of sudden infant death syndrome
(SIDS) have a serotonin (5-hydroxytryptamine
5-HT) abnormality in the brainstem that affects
responses to breathing and carbon dioxide, as
well as to temperature, blood pressure, and heart
rate. "These functions may be compromised during
sleep if a baby is lying face down and
rebreathing carbon dioxide," said lead study
author Hannah C. Kinney, MD, from Harvard Medical
School and Children's Hospital Boston in
Massachusetts. The findings appear to confirm the
hypothesis that SIDS the unexplained death of
an infant within a year of birth results from
lower levels, rather than an excess, of medullary
5-HT. This fits into the triple-risk model of
SIDS, suggesting it occurs when 3 elements come
together an infant with an underlying
vulnerability, in this case, a low serotonin
level a critical period of development during
the first year of life and an external stressor,
sleeping face down. "We call this a perfect
storm," said Dr. Kinney "You have a baby with
the underlying vulnerability but that becomes
unmasked when the baby is asleep and when the
baby undergoes stress." The study is published in
the February 3 issue of the Journal of the
American Medical Association
189
Genetic Disorders Web Sites
  • www.genetests.org - sources for
  • genetic testing
  • http//ghr.nlm.nih.gov information for
  • professionals and laypersons
  • www.ncbi.nlm.nih.gov/entrez/ -
  • information on 6000 genetically-
  • influenced diseases

190
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