Title: Genetics
1Genetics
- Genie Dorman, PhD, APRN, FNP-BC
- Summer, 2010
2Genetics 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)
3Definitions - 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.
4Definitions - 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
5Definitions - 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.
6Genetic 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.
7Genetic 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
8Genetic 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
9Genetic Disorders Classifiactions (cont.)
10Genetic 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
11Genetic 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
12Genetic 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)
13Genetic 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
14Overview 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)
16Trisomy 18 Definition
- Autosomal chromosomal disorder, trisomy of
chromosome 18 associated with severe mental
retardation and other congenital defects lt10
survive until 1st birthday
17Trisomy 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
18Trisomy 18 Signs and Symptoms
- Small for gestational age
- Hypertonia
- Feeding problems/ growth failure
- Severe global developmental delays
19Trisomy 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)
20Trisomy 18
21Trisomy 18
22Trisomy 18 Diagnostic Tests/ Findings
- Karyotype
- Fluorescent in-situ hybridization (FISH) analysis
- Results usually available within 48 hours
- Echocardiogram to detect congenital cardiac
defects
23Trisomy 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
24Trisomy 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
25Trisomy 18 Differential Diagnosis
- Trisomy 13 (Patau Syndrome)
- Cri-du-Chat (Cat-Cry Syndrome)
26Trisomy 21 Down Syndrome (DS)
27Down 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
28DS 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
29DS 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
30DS 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)
31DS Signs and Symptoms (cont.)
- - Penis appears small
- - Flattened occiputic
- - History of seizures- up to 13
32Down Syndrome
33Down Syndrome
34DS Differential Diagnosis
- Other genetic or chromosomal syndromes
35DS 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
36DS Physical Findings
- Signs of esophageal or duodenal atresia - 12
- Ligamentous laxity - 100
- Vision or hearing impairments - up to 90
- Obesity - 50 by early childhood
37DS 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
38DS Diagnostic Tests/ Findings
39DS 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
40DS Management/ Treatment (cont.)
- Nutritional Support
- Prophylactic antibiotics to prevent SBE, if
cardiac effects - Prompt consultation and referral for specialist
treatment of associated conditions
41Fragile X Syndrome
42Fragile 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
43Fragile 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
44Fragile 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
45Fragile X Syndrome Signs and Symptoms
- Developmental Delay
- Hyperactivity
- Speech delay perservative speech echolalia
- Poor gross motor coordination
46Fragile X Syndrome Signs and Symptoms (cont.)
- Stereotypes, e.g. talking to self, spinning, hand
flappping - Gaze aversion
- History of seizures - 17 to 50
47Fragile X Syndrome Differential Diagnosis
- Autism, Asperger syndrome, or pervasive
developmental disorder - Mental retardation with nonspecific etiology
- Klienfelter syndrome, Sotos syndrome
- Attention deficit hyperactivity disorder
48Fragile 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
49Fragile 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
50Fragile X Syndrome
51Fragile X Syndrome Diagnostic Tests/ Findings
- DNA analysis from whole blood in approved
labrotory to confirm diagnosis - Prenatal testing from chorionic villus or
amniocentesis sample
52Fragile 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
53Fragile 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
54Fragile X Syndrome Management/Treatment (cont.)
- Ophthalmologic evaluation - strabismus (40),
myopia - Developmental evaluation - mild to severe delays,
(usually moderate) - Anticipatory guidance
55Fragile 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
56Turner Syndrome
57Turner Syndrome Definition
- Chromosomal anomaly resulting in 45,X0 (female)
karyotype, with predictable associated signs and
symptoms
58Turner 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
59Turner Syndrome Signs and Symptoms
- Short stature with "square" appearance
- Low hairline
- Chronic ear infection
- Learning disabilities
- Lack of development of secondary sexual
characteristics
60Turner Syndrome Differential Diagnosis
- Congenital lymphedema without Turner's karyotype
- Coarctation of aorta without Turner's karyotype
61Turner 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
62Turner Syndrome Physical Findings (cont.)
- Scoliosis (10)
- Nail dysplasia
- Defective dentition
- High blood pressure
- Strabismus, amblyopia, ptosis
63Turner Syndrome
64Turner 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
-
65Turner 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
66Turner 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
67Turner Syndrome Management/Treatment (cont.)
- Genetic counseling
- Psychosocial support
- Assistance in school for learning disabilities
- Referral to cardiology for cardiac anomaly
diagnosis and treatment
68Turner Syndrome Management/Treatment (cont.)
- Referral to ENT, orthopedic, urology,
ophthalmology, pediatric dentist as needed - Prophylactic antibiotics for SBE if cardiac
effects present
69Klinefelter Syndrome
70Klinefelter Syndrome Definition
- Nonrandom association of physical
characteristics and learning and behavioral
disorders seen in males with the 47,XXY karyotype
71Klinefelter 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
72Klinefelter Syndrome Etiology/ Incidence (cont.)
- 11000 live births
- Most common cause of hypogonadism and infertility
in men
73Klinefelter Syndrome Signs and Symptoms
- Tall male, especially at adolescence and beyond
- Slow, incomplete pubertal development
- Behavioral and psychiatric disorders (shy,
immature, anxious, aggressive, antisocial)
74Klinefelter Syndrome Signs and Symptoms (cont.)
- Thin child
- Language impairment
75Klinefelter Syndrome Differential Diagnosis
- Marfan syndrome
- Sotos syndrome
- Trisomy 8p
76Klinefelter Syndrome Physical Findings
- Tall for age, with disproportionate lower limb
length - Gynecomastia
- Small, firm testes
- Cryptorchidism
- Small phallus
- Hypospadias
77Klinefelter Syndrome
78Klinefelter Syndrome Diagnostic Tests/ Findings
- Chromosome analysis yields 47, XXY karyotype
- High FSH, LH and low testosterone levels
79Klinefelter Syndrome Management/Treatment
- Early intervention for learning disorders
- Counseling/ therapy for behavioral disorders
- Psychosocial support for family
- Genetic counseling
80Klinefelter 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
81Tay-Sachs Disease
82Tay-Sachs Disease Definition
- Inborn error of metabolism resulting in
neurologic degenerative disease and death,
usually by 3 years of age
83Tay-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
84Tay-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
85Tay-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
86Tay-Sachs Disease Signs and Symptoms (cont.)
- Frequent upper respiratory infections
- Apathy, irritability
- Seizures
- Deafness/ Blindness
- Feeding problems
87Tay-Sachs Disease Physical Findings
- Other inborn errors of metabolism
- Leukodystrophies
- Muscular dystrophy
88Tay-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
89Tay-Sachs Disease
90Tay-Sachs Disease
91Tay-Sachs Disease Diagnostic Tests/ Findings
(cont.)
- Decerebrate posturing
- Dysphasia
- Eventual vegetative state
- Serum enzymatic assay yields deficiency of
hexosaminidase A
92Tay-Sachs Disease Management/ Treatment
- Genetic counseling
- Primary prevention via carrier screening
- Secondary prevention via prenatal diagnosis and
elective termination of pregnancy
93Tay-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
94Marfan Syndrome
95Marfan Syndrome Definition
- Inherited disorder of connective tissue affects
the skeletal, cardiovascular and ocular systems
96Marfan Syndrome Etiology/ Incidence
- Autosomal dominant inheritance of defective
fibrillin gene mapped to chromosome 15 15
sporadic mutation - Incidence is 120,000
97Marfan 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
98Marfan Syndrome Signs and Symptoms (cont.)
- Vision impairment
- Normal intelligence with learning disorders,
attention deficit hyperactivity disorder (40)
99Marfan Syndrome
100Marfan Syndrome
101Marfan Syndrome Differential Diagnosis
- Beals syndrome (congenital contracultural
arachnodactyly) - Homocystinuria
102Marfan Syndrome Physical Findings
- Skeletel
- - Loose joints
- - Scoliosis (60)
- - Pectus excavatum or carinatum
- - Narrow Palate
-
103Marfan Syndrome
104Marfan 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
105Marfan Syndrome Physical Findings (cont.)
- Murmur indicative of mitral valve prolapse
- Ocular - upwardly dislocated lens, retinal
detachment - Myopia
106Marfan 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
107Marfan 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
108Marfan 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
109Marfan 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
110Marfan 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
111Hurler Syndrome (MPS IH)
112Hurler 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
113Hurler Syndrome Etiology/ Incidence
- Deficiency of enzyme a-L-iduronidase autosomal
recessive inheritance - 1100,000
114Hurler 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
115Hurler Syndrome
116Hurler Syndrome
117Hurler Syndrome Signs and Symptoms (cont.)
- Vision and hearing impairments
- Joint limitations and contractures
- Short stature
118Hurler Syndrome Differential Diagnosis
- Other progressive neuropathies and inborn errors
of metabolism, particularly other
mucopolysaccharidoses and thyroid deficiency
119Hurler Syndrome Physical Findings
- Skeletal abnormalities, including spinal
anomalies/ gibbus formation - Macrocephaly, scaphocephaly
- Hepatosplenomegaly
120Hurlers Syndrome
121Hurler Syndrome Physical Findings (cont.)
- Clouded corneas
- Inguinal/ umbilical hernia
- Valvular heart disease coronary artery disease
122Hurler Syndrome Diagnostic Tests/ Findings
- Prenatal diagnosis with amniocentesis or
chorionic villus sampling and enzyme analysis - Postnatal via serum and urine enzyme analysis
123Hurler Syndrome Management/ Treatment
- Genetic counseling
- Psychosocial counseling
- Anticipatory guidance
- Early intervention appropriate school placement
with supports as needed
124Hurler 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
125Hurler Syndrome Management/ Treatment (cont.)
- To date, enzyme replacement therapy not effective
126Prader-Willi Syndrome
127Prader-Willi Syndrome - Definition
- Congenital disorder characterized by voracious,
uncontrollable apetite and obesity
128Prader-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
129Prader-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
130Prader-Willi Syndrome Differential Diagnosis
- Other neurological and musculoskeletal disorders
with early hypotonia (including cerebral palsy)
and developmental delay
131Prader-Willi Syndrome Physical Findings
- Obesity
- Small hands and feet
- Small genitalia
- Cryptorchidism
- Short stature
- Scoliosis
132Prader-Willi Syndrome
133Prader-Willi Syndrome
134Prader-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
135Prader-Willi Syndrome Diagnostic Tests/ Findings
(cont.)
- Growth Hormone deficiency frequent, but not
universal
136Prader-Willi Syndrome Management/ Treatment
- Behavioral therapy for control of eating and
other problem behaviors - Genetic counseling
- Early intervention and appropriate school
placement with supports
137Prader-Willi Syndrome Management/ Treatment
(cont.)
- Psychosocial support for family and child
- Refer to endocrinology for evaluation and
management of Growth Hormone deficiency
138Cerebral Palsy (CP)
139Cerebral 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
140Cerebral 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
141Cerebral 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
142Cerebral Palsy Signs and Symptoms
- Movement or posture abnormality that evolves with
growth, but is not itself progressive - Delays in reaching developmental milestones,
especially motor
143Cerebral 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
144Cerebral 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
145Cerebral Palsy
- Vision impairment (50)
- Hearing impairment (10)
- Seizures (35 to 50)
- Mental retardation (50 to 75) more common with
greater physical disability
146Cerebral Palsy Differential Diagnosis
- Neurodegenerative disorders such as Duchenne
muscular dystrophy - Inborn errors of metabolism
- Brain tumor
- Hydrocephalus
- Subdural hematoma
- Dystonias
147Cerebral 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
148Cerebral Palsy Physical Findings (cont.)
- Hip click or clunk on Barlow maneuver or Ortolani
test - Movement related muscle spasms
- Low weight for height
- Neuromuscular scoliosis
149Cerebral 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
150Cerebral Palsy Management/Treatment
- Coordinate interdisciplinary management to
promote optimum health and function - Enroll in early intervention services
151Cerebral 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)
152Cerebral Palsy Management/Treatment
- Functional therapies to build on strengths and
promote compensation for physical impairments - Parent/ family support for positive coping and
stress relief
153Cerebral Palsy Management/Treatment
- Spasticity relief
- Enternal medication - lioresal, diazepam,
dantrium, sodium, tizanidine hydrochloride - Selective dorsal root rhizotomy
154Cerebral Palsy Management/Treatment
- Nutritional support
- Ensure appropriate education with supportive
services and therapies
155Spina Bifida
156Spina Bifida Definition
- Congenital multisystem defect resulting from
failure of neural tube closure during early
embryonic development one of several "neural
tube defects"
157Spina Bifida
158Spina 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)
159Spina 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
160Spina Bifida Signs and Symptoms
- Urinary "dribbling", unable to achieve urinary
continence - Frequent urinary tract infections
- Chronic constipation, difficulty with bowel
continence
161Spina 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
162Spina Bifida Differential Diagnosis
- Syndromes of which spina bifida is associated,
e.g., Meckel-Gruber syndrome
163Spina 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
164Spina 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)
165Spina 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
166Spina Bifida Physical Findings (cont.)
- Abnormal neonatal reflexes in lower extremities
- Decreased or absent anal wink
- Atrophied lower extremity/ hip muscles
167Spina Bifida Physical Findings (cont.)
- Scoliosis, kyphosis
- Obesity in older children and adolescents (gt50)
- Neurogenic bowel and bladder
- Latex sensitivity (gt40)
168Spina 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
169Spina Bifida Diagnostic Tests/Findings (cont.)
- Postnatal diagnosis made on clinical basis
- Hydrocephalus after birth, increasing head
circumference out of proportion to other growth
parameters
170Spina 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
171Spina 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
172Spina Bifida Management/ Treatment (cont.)
- Enroll infant in early intervention program as
soon as medically stable - Monitor for urinary tract infections expect less
common organisms
173Spina Bifida Management/ Treatment (cont.)
- Monitor development of orthopedic problems,
especially scoliosis and unilateral hip
subluxation or dislocation baseline and
follow-up radiographic studies
174Spina 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
175Spina Bifida Management/ Treatment (cont.)
- Monitor for skin breakdown
- Nutritional and behavioral intervention to
prevent obesity - Test for latex sensitivity (skin or RAST) latex
precautions
176Spina 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
177Spina 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
178Sudden Infant Death Syndrome (SIDS)
179Sudden 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)
180Sudden 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
181Sudden Infant Death Syndrome Signs and Symptoms
- Infant unexpectedly found lifeless after a period
of sleep
182Sudden Infant Death Syndrome Differential
Diagnosis
- Meningitis
- Intracranial hemorrhage
- Myocarditis
- Accidental trauma
- Child abuse
183Sudden 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
184Sudden Infant Death Syndrome Physical Findings
- Full cardiorespiratory arrest
- Unresponsive to resuscitation
185Sudden Infant Death Syndrome Diagnostic Tests/
Findings
- Diagnosis of exclusion, with autopsy and
investigation failure to find adequate cause of
death
186SIDS 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
187SIDS 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
188February 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
189Genetic 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
190The End