Syndromes and Conditions

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Syndromes and Conditions

• Terry Broda,
• RN, BScN, PHCNP, CDDN

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Presentation plan

• Genetics 101
• Overview of syndromes
• Fragile X
• Williams
• Prader-Willi
• Angelman
• Smith-Magenis
• Velocardiofacial
• Cornelia de Lange

• Rett
• Tuberous Sclerosis
• Neurofibromatosis type 1
• Cri-du-Chat
• PKU
• Smith-Lemli-Opitz

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GENETICS 101

• BEWARE OF HASTY GENERALISATIONS !
• important variations - medically, physically,
  cognitively behaviorally- are observed in
  individuals with the SAME genetic syndrome.

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Why should you test?

• Medical psychiatric issues
• Behavioral strategies
• Educational strategies
• Psychosocial considerations
• Parental closure

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GENOTYPE PHENOTYPE

• Phenotype The observable manifestations of a
  persons genotype (which includes physical
  characteristics such as height facial features,
  as well as predisposition to certain health
  problems heart disease, strabismus).
  
  
• Genotype A person s genetic makeup (the
  combination of genes of an organism or an
  individual).
  Dykens, Hodapp
  Finucane, 2000

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GENOTYPE PHENOTYPE

• 1972 William Nyhan proposed for the first time
  the notion of a behavioral phenotype
• Definition (Dykens, 1995)
• The heightened probability or likelihood that
  people with a given syndrome will exhibit certain
  behavioral developmental sequelae relative to
  those without the syndrome.

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Chromosomes

• 46 chromosomes organized in 23 pairs.
• These chromosomes contain condensed coils of DNA
  code in the form of genes.
• One member of each chromosome pair is inherited
  from your father the other from your mother,
  at conception.

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Chromosomes

• 22 of the 23 pairs of chromosomes are similar in
  both sexes are called autosomes.
• The chromosomes making up the 23rd pair are
  called the sex chromosomes because they determine
  a persons gender.
• In females, both sex chromosomes are alike are
  called chromosome X .

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Chromosomes
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Chromosomes

• Whereas, males have one chromosome X one
  chromosome Y.
• Therefore, it is the males spermatozoa that
  ultimately determines the sex of the fetus.

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Chromosomes
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Chromosome

• Each chromosome has a centromere
• Shorter section above the centromere is called
  the  p  arm
• ( p  for petite)
• Longer section below centromere is known as the
   q  arm
• ( q  for queue)
• A numeric system identifies all regions along
  both arms of each chromosome

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What exactly is a genetic mutation?

• When one or both copies of a specific gene
  presents an alteration in the DNA, which alters
  the designated function of that gene.
• For example,
• Deletion or microdeletion of part of a
  chromosome.

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DELETION
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Chromosomal Abnormalities

• Most common type ANEUPLOIDY an abnormal number
  of chromosomes ( or -).
• Monosomy (rare ex. Turner syndrome(45X0).
• Trisomy (ex. Down (21), 13, 18, Klinefelter
  (XXY))

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Mosaic?

• Normally, genetic anomalies occur during
  fertilization.
• Occasionally, the  genetic accident occurs
  later on during cell division.
• These individuals will have a mosaic version of
  the genetic syndrome will usually have less
  severe symptoms of the syndrome

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Genetic tests Karyotype

• The karyotype can identify cytogenetic
  abnormalities.
• Since 1960, we have been able to use karyotyping
  to diagnose several genetic syndromes (Down,
  Klinefelter, )

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The Karyotype
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FISHFluorescent In Situ Hybridization

• A specific molecular probe, labelled with a
  bright fluorescent chemical marker, is added to a
  chromosome preparation to find its
  sequence-specific match, at the molecular level.
• Useful in the diagnosis of deletion syndromes.

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Fragile X syndrome
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Fragile X Syndrome

• section q27.3 of the ? chromosome
• Prevalence
• 1 / 1500 males (but 1/4000 more likely
  (Fombonne, 1997)
• 1 / 2500 females ( 1/8000)
• 1 / 256 females are carriers of the premutation
  (Rousseau et al., 1995)
• 1/800 males are carriers
• Present in all ethnic groups

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Fragile X Syndrome

• Most common inherited cause of DD
• Females usually have milder symptoms
  (compensation by other X chromosome)
• Often initial dx of autism or PDD-NOS
• 39 of males with fragile ? had dx of autism or
  PDD in childhood
• 16-17 of adults with fragile ? meet DSM
  criteria for autism
• 0-16 males with dx of autism test for fragile
  ?

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Fragile X Syndrome

• Fragile X syndrome is associated with an expanded
  repetition of the trinucleotide CGG which, in
   normal  persons, is repeated between 6 and 50
  times.
• 1) normal 6 - 50 CGG repeats
• 2) premutation 50-200 CGG repeats (FXTAS)
• 3) full mutation 200 CGG repeats
  (Fragile X)
• An FMR1 gene with a full mutation becomes
  inactive (methylated) cannot produce the FMR1
  protein (which plays a key role in brain
  development!).

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FXTAS Fragile X-associated Tremor/Ataxia Syndrome

• Progressive neurological disorder
• tremor ataxia
• Onset 50-60yrs (granddads of Fragile X kids)
• ONLY 20-30 of male carriers gt50 affected
• Often misdxed as atypical Parkinsons, multiple
  system atrophy, etc
• May provide insight into FMR1 gene deactivation

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Fragile X Checklist

• Hagerman, Amiri, and Cronister found that 45
  percent of males with a score of 16 or higher and
  60 percent of those with a score of 19 or higher
  had fragile X syndrome.
• Randi Hagerman, M.D., 2003

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Give 2 points if the feature is present, 1 point
if the feature was present in past or to a
borderline degree, and 0 points if the feature is
absent

•  Mental retardation Hyperactivity Short
  attention span Tactilely defensive Hand-flappin
  g Hand-biting Poor eye contact Perseverative
  speech Hyperextensible MP joints Large or
  prominent ears Large testicles Simian crease
  or Sydney line Family history of mental
  retardation

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Characteristic features

• Long face
• Prominent chin
• Prominent ears
• Larger head circumference
• Joint hypermobility/hyperextension
• Macro-orchidism

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Characteristic features

• Associated problems
• Strabismus (30-56)
• Recurrent serous otitis in childhood
• Dislocated hips, Scoliosis, hernias
• ADHD
• Mental retardation
• Autistic features (poor eye contact,
  hand-flapping, hand-biting)

• Tactile sensitivity
• Hyperextensible joints, flat feet
• Epilepsy (13 -50)
• Mitral valve prolapse (55), cardiac murmurs,
  hypertension
• Hypotonia, poor muscle tone in childhood

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FXS monitoring

• GERD
• Connective tissue pes planus, hyperflexibility
• Echocardiogam
• Vision hearing assessments
• (ophthalmology ENT)
• Speech language, OT, PT

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Shyness, social anxiety hypersensitivity

• Shy, timid personality
• Difficulties w/ peer interactions compared to
  interactions w/ adults.
• Excessive anxiety in new situations/environments.
• Hypersensitivity Tendancy to overreact to
  minor frustrations .

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Sensory Issues

• hyper arousal (sound of fluorescent lights, sight
  of too many decorations on wall)
• hypo arousal (sound of the teacher's voice,
  rather than the sound of the humming computer,
  fluorescent lights, and aquarium bubbler)
• sensory motor integration problems (including
  motor planning issues and fine motor weaknesses)
• tactile defensiveness (hypersensitivity to touch)
• difficulty in many new, confusing, or loud
  situations (because of a combination of sensory
  integration problems, anxiety, and attention
  deficit disorders)

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Tactile Defensiveness

• Affects 60-90 of FXS boys some FXS girls
• Overreaction to touch may avoid it
• Increased or decreased reactions to textures
• Clothing tags
• Need soft fabrics, no elastic cuffs or hems
• May prefer deep pressure of heavy clothing for
  increased feedback
• Have difficulty identifying objects or feeling
  receiving info by touch

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Tactile Defensiveness

• Firm, sure touches (handshakes bearhugs) may be
  tolerated better than light touch (tickling, soft
  touch of face)
• May prefer to be at end of the line, separate
  from crowd
• Infants may/may not be comforted by cuddling
• May not enjoy finger painting or other tactile
  art activities

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Tactile Defensiveness

• Difficulties with hygiene
• Bathing, face hair washing, shaving, nail
  cutting
• Dental visits may be difficult anxiety provoking
• Difficulties with eating
• Difficulty nursing from breast or bottle
• Strong food preferences related to textures of
  food
• Mouth stuffing of mouth, due to high cathedral
  palate, before realizing they may gag

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Remember

• A specific problem in the environment that can be
  modified will often effect a much larger
  improvement in behavior than medication!
• Maximize environment FIRST to get a reasonable
  baseline!

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Tactile Defensiveness strategies for
intervention

• Sensory diet individualized by an OT
• Uses neurodevelopmental therapy working with
  muscle tone sensory integration therapy (SI),
  involving all senses plus proprioreception (body
  position in space) vestibular (sense of gravity
  motion) input
• To find best combination timing of various
  sensory inputs decreases sensory overload

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Tactile Defensiveness strategies for
intervention

• Calming activities
• Rocking, swinging child
• Applying deep pressure
• Brushing childs skin with therapeutic brush
• Breaktime quieter area, playing computer game or
  listening to music or a story on headphones

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Tactile Defensiveness strategies for
intervention

• Environmental changes
• Increase natural light
• Limit/avoid exposure to loud situations
• Gradual desensitization to be able to tolerate
  more noise
• Adapted seating to help maintain upright posture
  with enough feedback
• Donut-shaped cushions, foam wedges

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Fine Gross Motor skills

• Movement therapy to improve balance, muscle tone
  proprioception
• dance, martial arts, sports, physical play
• Practice to improve use of
• pens/pencils for writing drawing
• utensils, scissors tools
• Keyboard (computer use)

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Oral-motor activities

• Activities to
• increase tolerance to touch around face mouth
• improve chewing, swallowing speaking
• Use of foods toys
• Blow toys, whistles, straws
• Crunchy or chewy food fruit snacks, celery,
  bagels, gum
• may decrease chewing on clothing, straps or
  skin!

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FXS ADL stuff

• Sleep
• PJs bedding
• Dark room/shades
• Soothing sounds, music
• Bedtime routine
• Eating
• Try various nipples/positions
• OT interventions for improved oral motor
  functioning

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FXS ADL stuff

• Dressing
• Remove tags, soft fabrics
• Buttons, snaps easier or T-shirts
• Shoes w/ velcro, curly laces
• Hygiene
• Desensitization to water on skin, calming
  strategies
• Pictures of sequence of activities
• Firm pressure with facecloth vs light strokes
• Dental
• Egg timer
• Desensitization books, visits w/ mom, sibling

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Fragile X Syndrome - attention
deficits/hyperactivity

• ? distractions study cubicles, desk at front of
  classroom or in calmer area facing a wall,
  periods of quiet time, decreased flow of traffic
  in room, adequate lighting heat
• ? use of visual cues (photos, etc)
• simple phrases concrete communication
• structure/routine/predictability

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FXS - Medication Options

• Medication vs. ADHD may be effective
• Children folic acid, stimulants (Ritalin,
  Dexedrine, Concerta), Clonidine
• Adults SSRI s, Buspar, mood-stabilizers,
  atypical antipsychotics (LAST CHOICE!)
• or combination Rx

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Fragile X Syndrome - more teaching approaches..

• Using pictograms, photos, objects of special
  interest or hands-on approach
• Using clocks, license plates cooking to help
  with number concepts
• Indirect explanation teach task to neighbour
• Apply persons strengths long-term memory,
  imitation skills, sense of humor
• Teach complete tasks present whole process (not
  step-by-step) use cover up method to follow
  sequence (Ø lose his place)

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Fragile X Syndrome - general approaches

• Do not force eye contact! (gaze aversion)
• Be careful invading personal space touching the
  person! (tactile sensitivity)
• Consistency important! (staffing, schedules,
  environment)
• Provide a book to carry with them containing
  info that may be difficult to remember

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Fragile X Syndrome - strategies vs. aggression

• Functional analysis
• A-B-C data collection
• Aggression may be preceded by giggling,
  non-compliance or avoidance
• May be d/t sensory processing problems sensory
  stimulation adds up during the day sensory
  activities may be more challenging later in the
  day ( ? demands are more difficult)
• higher incidence in adolescents hormones!

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Fragile X Syndrome - strategies vs. aggression

• Consider differentials
• Panic episodes fight or flight
• Mood disorders Depression or Bipolar disorder
• Seizure disorder
• Pain due to underlying medical problem

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Fragile X Syndrome - strategies vs. aggression

• Catch them being good! w/ reinforcement of
  behavior
• Specific interventional approaches ABA, Lovaas,
  token economy, time-outs
• Psychotherapy counselling (self-esteem,
  depression, anxiety/frustration, anger
  management, coping skills, social skills)
• Family Therapy

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Fragile X Syndrome - strategies vs. aggression

• Relaxation training, sensory stimulation/ sensory
  integration (OT), music
• Deep pressure massage
• Use of imagery
• Group Therapy Social Skills training (role
  playing)
• MedicationSSRIs vs anxiety, anti-psychotics (NOT
  first choice), Buspar

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Fragile X Syndrome - issues around sexuality

• Social Sexual skills
• Sex Ed. throughout beyond puberty
• Sexual abuse prevention information
• Psychotherapy counselling (self-esteem,
  depression, anxiety/frustration) (especially
  helpful for transition from parents home to
  independent living)

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Williams Syndrome
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Williams

• Strabismus
• Hyperacusis
• Cardiac malformations supravalvular aortic (75)
  or pulmonic stenosis, HTN, renal artery stenosis
• Renal anomalies w/ frequent UTI
• GI colic, reflux, constipation, ulcers,
  diverticuli
• Hernias (umbilical inguinal)
• Hyperlaxity in youth, contractures w/ age
• (risk of scoliosis, kyphosis, lordosis)
• Anxiety

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Williams monitoring

• At time of Dx
• PE Neuro exam
• Growth chart monitoring
• Consult cardio (echo Doppler)
• Consult Urology (U/S bladder kidneys)
• BUN, creatinine U/A
• Serum calcium Ca/creat in urine
• TFTs
• Opthalmology consult
• Developmental exam speech, cognition

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Williams monitoring

• Lifelong
• Cardiac BP X 2 arms annually (HTN risk) monitor
  for mitral valve prolapse, aortic insufficiency,
  arterial stenosis
• Ca in serum urine q. 2 yrs
• NO PEDIATRIC VITAMINS for WS kids (vit D)
• Monitor Tx constipation aggressively!
• Screen adults for sensorineural hearing loss,
  diabetes hypothyroidism

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WS - Intervention Strategies...

• Limit distractions study cubicles, desk at front
  of classroom or in calmer area facing a wall,
  periods of quiet time, decreased flow of traffic
  in room
• Encourage talking-through-it during
  problem-solving use of concrete
  objects/situations
  (real real-life situations)
• Encourage use of computers, calculators

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WS - Intervention Strategies...

• Tape recorded homework instead of written
  assignments
• Schedule with photos for daily activities
• Digital watches for telling time
• Music therapy/lessons
• Work people-oriented jobs vs. assembly-line type
  of work

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WS- Intervention Strategies...

• Hyperacusis
• ear plugs
• quieter environments, limited distractions
• provide warning prior to loud noises (alarms,
  sharpener, bells)
• comfort the person during their distress
• if room is too loud, leave the area
• hyperacusis vs. paranoia!

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WS - Intervention Strategies...

• Anxiety/Fear
• provide reassurance (but with set limits to
  ? attention-seeking behavior)
• Use distraction by changing topics after initial
  reassurances
• CBT-cognitive behavioral therapy
• Pharmacotherapy (with caution!) start with low
  doses since WS persons are Rx-sensitive (Ex.
  Ritalin, tricyclics ?)

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WS - Intervention Strategies

• Social skills
• Use buddy system to practice social skills,
  role-plays, social stories
• Topics to cover how to make keep friends,
  approaching others, taking turns, conversational
  skills, dealing with romantic issues sexuality,
  how why to be wary of strangers
• Group therapy can increase self esteem (but may
  not be appropriate for some d/t anxiety or ADHD)

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WS - characteristics

• Social skills
• theory of mind the ability to take on the
  perspective infer the mental state of another
  person
• Supports anecdotal impression of a sensitive,
  empathic, caring personality type
• Research to compare to autism (ToM, facial
  emotional recognition language)

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WS Chronic Constipation

• Monitoring
• Bristol stool form
• Positioning legs bent at the knee, with thighs
  elevated to h pressure on the abdomen
  (crouching) (rocking on the seat)
• Interventions
• Stool softeners to maintain regularity prevent
  rectal prolapse

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Bristol stool form

• From Understanding your Bowels
• by Dr. Heaton
• Website www.familydoctor.co.uk
• Check out the preview of the book youll find
  the form there

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Prader-Willi Syndrome
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Physical characteristics

• In infancy
• Hypotonia
• (floppy baby)
• Feeding difficulties w/ FTT
• Then btwn 1-6yrs old
• Rapid wt gain w/ central obesity
• Hyperphagia w/ Food-seeking, hoarding foraging
  behaviors

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Hypothalamic involvement

• Hypothalamus, responsible for various functions
  including satiety and thermoregulation
• Precise mechanism involved in PWS still uncertain

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Common characteristics

• Obesity
• Short stature w/ decreased levels of growth
  hormone
• Small hands feet
• Almond-shaped eyes
• Hypogonadism

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Prader-Willi

• Obesity-related illness
• Diabetes
• HTN
• Hyperlipidemia
• Sleep apnea (ST memory impairment)
• Pica
• Cellulitis (skin-picking)

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Prader-Willi

• Elevated tolerance to pain
• (may have injury or but may not c/o pain)
• Decreased or absent vomit/gag reflex
• Thick viscous saliva increased caries
• Thermoregulatory instability (masked fever)
• Osteoporosis( increased risk of ), scoliosis,
  kyphosis

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Prader Willi monitoring

• Developmental educational assessment along with
  speech therapy assessment
• Assess males for cryptorchidism
• Strabismus in infants children
• X-rays to r/o scoliosis
• Bone density to r/o osteoporosis, most likely
  will need calcium supplementation
• Annual BMI
• HgbA1C for those with significant obesity
• Sleep study to r/o sleep apnea
• Psych assessment to r/o OCD psychosis

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PWS - Intervention Strategies...

• Food issues
• DO NOT USE FOOD AS A REWARD OR PUNISHMENT
• Caloric intake 800-1200cal/day
• Calcium vitamin supplements
• Limit access (locks on cupboards, fridge)
• Environmental changes (PWS residences)

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PWS - Intervention Strategies...

• Tantrums (verify if due to food issues!!)
• DO NOT ARGUE
• BE CONSISTENT (provide structure routine)
• set firm limits
• written rules/contracts (with them)
• allow time to settle
• change the environment (quiet area)
• diversion, humor (but not sarcasm)

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PWS - Intervention Strategies...

• Skin-picking
• Reinforce behavior
• cut nails short
• encourage alternative activities/distractions
  collages, scrapbooks, Play-Doh, playing cards,
  hand cream, puzzles (scheduling)
• bandaids may be helpful as an initial layer to be
  removed before skin-picking can occur (liquid
  bandaid, long term drsg-duoderm/allevyn)
• HANDWASHING!!!!!

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PWS - Intervention Strategies...

• Educational strategies
• a.m. classes when person is more alert
• consistency with breaks, lunchtime
• demos, pictures, models to teach
• specific choices (ex. red or blue crayon not
  which one)
• encourage helping others
• using puzzles (jigsaw word search)
• extra physical activities

75
Prader-Willi Syndrome- Intervention Strategies...

• Psychiatric considerations
• OCD (food rituals - but may also make poor food
  choices, hoarding, ordering, repeating)
• depression
• psychosis
• anxiety

76
PWS - Intervention Strategies...

• Pharmacotherapy
• Rx to decrease appetite are not effective!
• estrogen/progesterone testosterone may be
  helpful for sexual development
• calcium supplements (osteoporosis)
• growth hormone (increases height energy)
• SSRIs
• atypical antipsychotics (S/E!)

77
Angelman Syndrome
78
Angelman

• Epilepsy (86-96)
• Ataxia (100)
• Scoliosis
• Strabismus (42-75)

79
Angelman monitoring

• Baseline MRI EEG r/t Epilepsy
• MSK exam to assess ataxia scoliosis
• Ophthalmology consult to r/o strabismus assess
  visual acuity
• Assess for reflux
• Consults for communication educational
  strategies, PT OT
• Assess monitor for constipation

80
Angelman Syndrome-Intervention Strategies...

• Communication strategies
• Offer choices (2) provide item ASAP
• Yes/No cards
• Sign language
• PECS (communication book)
• Laminated wooden blocks with words

81
Angelman Syndrome-Intervention Strategies...

• Increase physical activities
• Hippotherapy
• Hydrotherapy/swimming (SUPERVISION)
• action-reaction/remote control toys
• ROM exercises
• Therapy ball, floor exercises

82
AS-Intervention Strategies...

• Vs Drooling
• Flavoured extract applied to oral mucosa under
  tongue
• 1 Atropine ophthalmic gtts 1 gtt orally qd
• Robinol (glycopyrolate) orally, scopolamine
  patch
• Botox injections orally q.3 months
• bandana, bib with design (for salivation)
• oral stimulation using a straw, bagels, peanut
  butter, gum
• Surgery removal of salivary glands, redirection
  of salivary ducts

83
AS Intervention Strategies...

• For sleep problems
• Active day with exercise!
• Establish a routine HS pm (naps)
• Snack before bed
• Very dark bedroom, dark blinds/curtains
• Weighted quilt/blanket
• Waterbed
• Split-style door
• White noise machine/ fan/ soft music

84
AS Intervention Strategies...

• For sleep problems
• Egg crate mattress, soft blankets
• Warm bath before bed
• Warm milk hs
• Warm H2O bottle on abdomen
• Warm socks!
• Medication Strategies
• anti-epileptic medication (for sz mood )
• melatonin (to regulate sleep)

85
Smith-Magenis Syndrome
86
Smith Magenis

• Vision problems myopia, strabismus (30-100)
• Infections onychotillomania (30)
• SIB Polyemboikolomania (25)
• ENT problems otitis hearing loss, anomalies of
  the palate (63-81)
• CV abnormalities ASD, VSD, valvular stenosis
  (27-29)
• Scoliosis (42-65)
• Renal abnormalities (28-35)
• Pain/heat tolerance Peripheral neuropathy (75)

87
Smith Magenis monitoring

• At Dx
• ROS PE Neuro exams
• Renal U/S, Echocardiogram, Spinal x-rays
• Ophthalmology consult, ENT consult, PT, OT
• Speech evaluation, audiology
• Bldwk immunoglobulins, lipids, TFTs
• Sleep diary sleep apnea studies PRN

88
Smith Magenis monitoring

• Annually
• PT, OT, Speech evaluation
• TFTs
• Fasting lipid profile
• U/A
• Monitor for scoliosis
• Ophthalmology
• ENT otitis sinus problems
• Audiology sensorineural hearing loss

89
Smith Magenis monitoring

• PRN assessments
• EEG (CT, MRI may also be needed)
• Urology W/U if frequent UTIs
• If microdeletion extends into 17p12 then adrenal
  function must be assessed (SMS 17p11.2)

90
Strengths Weaknesses

• Strengths
• LT memory for places, people
• Letter-word recognition
• Weaknesses
• Sequential processing
• Visual ST memory

91
Smith Magenis Syndrome- Intervention
Strategies...

• Educational strategies
• sign language, speech therapy
• structured activities, routines
• small classes, individual attention (designate
  them as the teacher s helper)
• computers
• well-matched with teacher ( Ø power struggles)
•  use creativity, humor

92
SMS Intervention Strategies...

• For sleep problems
• (see AS slides for other interventions)
• very dark bedroom, dark blinds/curtains
• weighted quilt/blanket (massaging hands feet
  may also help)
• split-style door, enclosed bed (Vail bed)
• SAD lights (pineal gland) (inverted circadian
  rhythm)
• Rx melotonin (2.5-5mg), ß1-blockers, GH
• in one study, tantrums nap attacks often
  occurred midday evening when melatonin levels
  were elevated (De Leersnyder, et al, 2001)

93
SMS Intervention Strategies...

• For aggression SIB
• CAREFUL W/ PHYSICAL INTERVENTION
• try to redirect to another activity
• try to determine triggering factors eliminate
  them
• applying nail polish may decrease
  onychotillomania
• Rx oral contraceptives, SSRIs, mood-stabilizers
  (AEDs)
• There has been a relative calming noted in
  adulthood

94
SMS other concerns...

• Tactile defensiveness may present as stripping
  of clothes!
• Hugging can be aggressive rib-crushing
• Polyembolokoilamania (orifice-stuffing) can
  include vagina/rectum (vs ? abuse)
• Cavities large pulp chambers low levels of
  enamel
• Peripheral neuropathy (numbness/tingling in
  fingers toes) (SIBhand-biting?)

95
Velocardiofacial Syndrome
96
VCFS/22q-

• ENT Cleft palate, otitis, deafness
• Visual problems cataracts, tortuousity of
  retinal vessels (30)
• Cardiovascular abnormalities (85) R aortic arch
  (52), Tetralogy of Fallot (21), ASD, VSD (62)
• Immune system problems (vaccines not effective)
  (r/t thymus)
• Hyper/hypothyroidism
• Scoliosis, arthritis
• Renal abnormalities absent/dysplastic/multicystic
  kidneys, hypospadius, reflux, obstructive
  uropathy
• Mental health Bipolar disorder (68),
  schizophrenia (29)

97
Strengths weaknesses

• Strengths
• Verbal IQ processing
• Rote verbal learning verbal memory
• Auditory perception memory
• Word-reading decoding
• Weaknesses
• Non-verbal processing, facialprocessing recall
• Visual-spatial skills
• Phonological processing
• Math reading comprehension

98
Velocardiofacial Syndrome- Intervention
Strategies...

• speech therapy (ARTICULATION!)
• provide structure
• use ? reinforcement
• encourage self-talk/thinking aloud to decrease
  impulsivity
• computers to help with reading spelling, also
  with math abstract problem-solving

99
VCFS - Intervention Strategies

• Medication strategies
• mood-stabilizers (AED s)
• avoid SSRI s/tricyclics - may induce mania
• Ritalin may also induce hypomania
• may require antipsychotics (more studies needed)

100
VCFS

• New resource book
• MISSING GENETIC PIECES Strategies for Living
  with VCFS, The Chromosome 22q11 Deletion
• available at
• http//www.winmarkcom.com/vcfs.htm
• Cost 30.00

101
Cornelia de Lange Syndrome
102
CdLS

• DISCOVERED MAY 2004 , PHILADELPHIA
• Gene discovered for Cornelia de Lange Syndrome
• Dr. Ian Krantz (Childrens Hosp) Dr. Laird
  Jackson (Drexel University College of Medicine)
• Large gene, NIPBL, on chromosome 5
• NIPBL Nipped-B like because human gene
  produced similar proteins to the fruit fly gene
  which produced flies with an abnormal wing
  (looked as if a bite was taken out of it).

103
Cornelia de Lange

• Eye problems myopia/ptosis/nystagmus (57),
  conjunctivitis (67)
• GI problems (75) GERD (30)
• Ear problems (73) hearing loss (60)
• Peripheral neuropathy
• Seizures (23)
• Hernias (hiatal, diaphragmatic, inguinal)

104
CdLS monitoring

• GERD evaluation, monitor for FTT
• ENT, audiology ophthalmology
• X-rays of upper extremities
• radioulnar synostosis
• Monitor for cardiac renal abnormalities
• Echocardiogram, renal U/S, vesicoureterogram
  (VSUG), urologic exam to look for cryptorchidism
  hypospadius
• Neurology evaluation EEG
• CBC PRN (bruising, bleeding, anemia suspected)

105
CdLS - Intervention Strategies

• Structure routine
• Schedule (with photos or words)
• Communication strategies
• Pointing
• Yes/No cards
• Sign language
• PECS
• Speech therapy

106
CdLS - Intervention Strategies

• Teach relaxation
• Music
• Hammock
• Special doll/toy
• Teach ways to decrease agitation
• Squeezeball
• Deep breathing exercises
• Time out chair/area that can be requested

107
Gastro-esophageal Reflux

• Interventions (without an Rx)
• Fill in food diary
• Avoid alcohol, chocolate, coffee, spicy foods,
  fatty foods, tomatoes, onions, citrus other
  acidic fruits
• Smaller meals, more frequently
• Avoid eating 2 hours before going to sleep
• Decrease weight stop/cut down on smoking
• Raise HOB 6-8 to sleep (2-3 pillows)
• Observe for vomiting with blood, coffee grains

108
CdLS - Intervention Strategies

• Tantrums or sleep problems may be d/t
• GERD
• pain/neuropathy (otitis, conjunctivitis, bunions)
  
• cold feet (anti-slip socks!)
• Rx  Ritalin vs ADHD, Elavil Neurontin vs pain
  affect, analgesics (Tylenol)

109
CdLS

• Excellent resource book,
• Self-injurious behaviour in Cornelia de Lange
  Syndrome A Guide for Parents and Carers,
• available FREE on line at
• www.cdlsworld.org/books/behaviour/index.php

110
Rett Syndrome
111
Rett

• Skin breakdown hand-mouthing, immobility
• Seizures
• Hyperventilation/breath-holding spells
• Scoliosis (Tx braces, Sx)
• Constipation
• Poor circulation cold hands feet

112
Rett syndrome monitoring

• Monitor Tx constipation
• (Microlax better than MOM)
• Monitor Tx GERD
• Consult OT (sensory integration
  proprioreception, music therapy)
• Consult PT (ROM, hydroTx, orthotics)
• Consult speech therapist for assistive
  augmentative communication (AAC) vs dysphagia
  chewing problems
• EEG for sz investigation

113
Rett syndrome Rx

• Vs feeding growth retardation
• caloric supplements
• Gastrostomy button placement
• Vs seizures AEDs
  (but sensitive, avoid polypharmacy)
• AVOID tricyclic antidepressants (TCAs),
  thioridazine (Mellaril) as they can provoke
  prolonged QT interval

114
Rett syndrome Rx

• Vs skin breakdown d/t hand-mouthing
• Hand-holding, distraction/stimulation (favorite
  toy, keys), massage, gloves/socks
• Arm/hand/elbow splints PRN
  (LEAST restrictive!)
• Vs bruxism
• jaw massage, orthodontics, soft towel, teething
  object
• INDIVIDUALIZED APPROACH!

115
Rett syndrome Rx

• Vs hyperventilation, air swallowing, GERD
  constipation
• No Tx for breath-holding air swallowing
• Positioning after meals vs GERD
• Avoid trigger foods for GERD
• Monitor stools (frequency consistency)

116
Rett syndrome Rx

• Vs sleep problems
• Melatonin
• Vs screaming spells
• ID causes!
• Assess for pain (PMS, GERD, etc)
• Gradual transitions, with parent
• Music
• Massage
• Warm baths

117
Rett Syndrome Communication

• speak to you through the eyes
• Eye-pointing behavior
• Comprehension gt expression!
• Often prefer male caregivers visitors!
• Some have autistic features
• Allow time to express wants
• Parents are excellent resources!
• Immobilization of hands may improve focus on
  conversation
• Speech Tx AAC

118
Tuberous Sclerosis
119
Tuberous Sclerosis

• Tubers, subungal fibromatas (PAIN!)
• Epilepsy (90)
• Rhabdomyomata, angiomata (47-67)
• Renal deterioration failure (45-81)
• Ocular issues hamartoma, astrocytoma (up to
  75 )
• Hamartoma that may lead to liver failure
• (up to 75)

120
Tuberous Sclerosis

• Teeth, skin nail findings
• Dental pits (48-100)
• Gingival fibromas (33)
• Facial angiofibromas/forehead plaques (77-86)
• Hypomelanotic macules (ash-leaf spots) (3 )
  (95)
• Shagreen patches (48-54)
• Confetti spots
• Ungual fibromas (nails) (11-23 ado 88 adults)

121
Tuberous Sclerosis

• Developmental disability
• Autism
• PDD
• OCD
• Anxiety
• Mood disorders
• Chronic sleep disorders

122
TS monitoring

• Abdominal (renal) U/S q.1-3 yrs
• if abN, CT or MRI
• BUN, creatinine q. 6 months
• Cranial CT/MRI for kids ados
• EEG for sz F/U
• Chest CT PRN
• ECG initially echocardiogram PRN
• Ophthalmology consult
• Perform initial exam with Woods lamp to assess
  dermatological findings

123
Tuberous Sclerosis Rx?

• Vs seizures
• Vigabatrin vs infantile spasm have proven more
  effective than ACTH
• Other AEDs valproate, lamotrigine topiramate,
  carbamazepine, clobazam
• Surgery to remove tubors, VNS
• Vs sleep problems melatonin
• Rx vs ADHD ? interactions with AEDs
• Vs facial angiofibromas laser Tx

124
Neurofibromatosis type 1
125
Neurofibromatosis-type 1 (NF1)

• 1/3000 - 1/4000
• Café au lait spots (almost 100)
• Axillary inguinal freckling (90)
• Multiple palpable dermal fibromas
• Lisch nodules (small tumors of the iris)
• Bony lesions (scoliosis, vertebral dysplasia,
  pseudoarthrosis overgrowth)

126
NF1

• Plexiform neurofibromas
• Optic CNS gliomas
• Peripheral nerve sheath tumors
• Vasculopathy
• risk increases with age

127
NF1

• Short stature (1/3)
• Macrocephaly
• Learning disabilities (subtle to severe in
  40-60), IQlt70 in 4-8 only
• Cardiac complications (pulmonary valvular
  stenosis, HTN)
• Increased risk of ADHD

128
NF1 monitoring

• At Dx
• ROS PE (derm, ophthalmo, skeletal neuro
  systems)
• Developmental assessment of children
• Then
• Annual PE
• Annual ophthalmology as child
• Regular BP monitoring
• PT, OT, Speech evaluation PRN

129
NF1 monitoring

• Then
• Surgical consultation PRN for fibroma resection
• Ortho consult PRN (pseudoarthrosis, scoliosis)
• HTN should be thoroughly investigated (abdominal
  MRI, 24-hr urine collection)
• PRN nephrology, neurology, vascular surgery

130
Cri-du-Chat syndrome
131
Syndrome Cri du Chat (5p-)

• 1/20,00-1/50,000
• High-pitched cat-like cry (d/t abnormal laryngeal
  development)
• Hypotonia
• Neonates Low birth weight, FTT (47), reflux
  vomit (42)
• Microcephaly with round (moon) face
• Hypertelorism (widely spread eyes), strabismus
• Epicanthal folds
• Flattened, widened nasal bridge
• Micrognathia
• Low-set often malformed ears
• (increased sensitivity to noise in 70-80)

132
Syndrome Cri du Chat (5p-)

• Dribbling (d/t weak muscles) constipation
  (70!)
• Increased risk of URTI dental problems
• Congenital heart disease, renal anomalies
  scoliosis may occur
• Severe to profound developmental delay
• Delayed, limited speech
• ADHD
• Sleep problems (50)
• SIB (92), aggression, stereotypies
• with age, clinical picture becomes less obvious
  (may resemble AS)

133
SCDC monitoring/intervention

• Speech language, OT, PT
• Early intervention programs
• Psychology
• PRN
• Cardiology
• GI
• Ophthalmology
• Orthopedics
• Urology

134
Phenylketonuria (PKU)
135
Phenylketonuria (PKU)

• Inborn error of metabolism
• Phenylalanine hydroxylase (PAH) deficiency
  results in intolerance to the dietary intake of
  the essential amino acid phenylalanine (Phe) and
  produces a spectrum of disorders including
  phenylketonuria (PKU), non-PKU hyperphenylalaninem
  ia (non-PKU HPA), and variant PKU
• Autosomal recessive

136
PKU

• Blond/light hair (increased phenylalanine
  inhibits melanogenesis)
• Sclerodermoid changes
• Generalized hypopigmentation
• Blue eyes
• Eczematous dermatitis
• Developmental disability
• Hyperreflexia, spasticity
• Seizures
• SIB, aggression, ADHD, pica

137
Living with PKU

• In the hours after a protein-rich meal, persons
  with PKU will often experience
• Nervousness
• Fatigue
• Difficulty concentrating
• Problems memorizing
• Difficulty completing complex tasks

138
Phenylalanine

• Essential amino acid the body cannot produce it
  so it comes from food
• Source of Phe in foods containing proteins that
  break down into amino acids
• Meat substitutes (fish, eggs, nuts grains,
  legumes)
• Milk products
• Cereals
• Fruits vegetables
• Aspartame

139
Nutritional approach

• In children (GOALS)
• - Normal brain development
• Prevent or minimize brain damage and achieve
  their intellectual potential
• Normal growth and maintenance of appropriate
  blood levels (Phe) with adequate tyrosine,
  protein calories
• Phe blood level btwn 120 and 360 µmol/L

140
Nutritional approach

• Goals in persons with DD (of any age)
• Maintain adequate level of phenylalanine
• Very good control 120-360 µmol/L
• Good control lt 600 µmol/L
• Decreases challenging behavior

141
Dietary principles

• Monitor Phe levels
• Assure adequate protein caloric intake to keep
  Phe levels within safe range
• Consistency (no cheating!)
• Dietician dietary intervention for life needs
  to start ASAP!

142
Recommandations

• Phenylalanine
• A restricted intake of Phe is necessary but a
  minimim amount is required by the body.
• Low Phe levels can lead to other problems
  lethargy, anorexia, anemia, dermatological issues
  and diarrhea.
• Females gt 19yrs 220-700mg/day
• Males gt 19yrs 290-1200mg/day

143
Diet

• Special beverages
• An essential part of the diet, provide adequate
  requirements for energy, protein, vits minerals
  
• Milk substitutes, special formulas, amino acid
  bars
• Special products
• Low-protein formulation products cereals, egg
  substitutes, chocolate which allow for variety
  provide adequate caloric intake
• Cereals
• regular or low protein (low in phenylalanine)

144
Diet

• Fruits vegetables
• No meat or substitutes
• No milk products or limited amounts
• No restriction (other than for weight concerns!)
•  Tang , regular colas, tea, coffee, iced tea,
  vegetable oil, Jello, clear candies, honey,
  regular popsicles
• ?ALL foods can contain some Phe so it NEEDS to
  be calculated
• Can be used as a limited intake treat.
• ? 15mg 1 treat

145
Diet

• Frequent bldwk to monitor Phe levels in early yrs
  
• (q. week eventually q. month)
• Abnormal bloodwork
• wait for 2 elevated Phe results before adjusting
  the diet then suggested Phe dietary decrease by
  10
• Regular monitoring of weight adjust diet
  accordingly

146
PKU monitoring

• Maternal PKU
• monitor bldwk for Phe 2X/ week during pregnancy
• dietary interventions during pregnancy (mom w/
  PKU) to prevent complications (miscarriage,
  congenital heart defects microcephaly DD)
• PT, OT
• Neurology
• Dermatology

147
Smith-Lemli-Opitz
148
Smith-Lemli-Opitz (SLO)

• 1/40,000-1/60,000
• Autosomal recessive disorder of cholesterol
  metabolism
• Prenatal growth deficiency, feeding problems as
  babies
• Epicanthal folds, ptosis, cataracts (12-18)
• Microcephaly
• Micrognathia (small jaw), retrognathia
• Small upturned nose, depressed nasal bridge

149
SLO

• 2nd 3rd toe syndactyly (95), short thumbs,
  postaxial polydactyly
• Cleft palate (37-52)
• Hypotonia
• Renal (13) uro-genital malformations
  (hypospadias, female genitalia in boys) (urinary
  tract abnormalities in up to 60)
• Low blood cholesterol levels
• Hearing loss

150
SLO

• Behavioral difficulties, SIB aggression
• Sleep problems
• Autistic features
• Cardiac defects (36-38)
• Dermatological problems (rashes, eczema (10)
  photosensitivity)
• GI issues (25-29) Hirschsprungs disease ( Ø
  nerves in colon), GERD (may improve w/ age),
  constipation

151
Smith Lemli-Opitz

• Particular behavior (50)
• Opisthokinesis arching and contorsions of the
  trunk
• ? head-banging
• SIB (71)
• Self-biting (54)
• Head-banging on objects (36)

152
SLO-strategies

• Dietary therapy/supplementation vs cholesterol
  deficiency (seems to help w/ photosensitivity
  rashes)
• Hearing tests/audiology
• OT speech Tx for feeding problems
• Neuro consult PRN
• Ophthalmology PRN
• Cardiology W/U (echo) at dx PRN

153
Smith Lemli-Opitz

• Intervention
• Cholesterol supplements, biliary acid
  (ursodesoxycholic acid)
• Questions doses, duration, sources
• Effects
• Decrease irritability, hyperactivity, SIB,
  tactile defensiveness
• Increases attention, social behavior, sleep
  quality

154
SLO-strategies

• GI W/U (LFTs bili) at dx, Ba enema /or bowel
  bx (r/o Hirschsprungs) if chronic constipation
• U/S of urinary tract at dx F/U w/ urology PRN,
  surgical interventions may be necessary