PTRS 833 - Genetic Syndromes, Motor, and Intellectual Disabilities

What to look at when identifying a potential genetic disorder?

- family hx

- dysmorphic features

- anatomic / physiologic abnormalities (e.g. brain formations)

- neuromotor assessment (weakness, tone abnormalities, motor control / dyscoordination problems, motor development delay, sensory integration problems)

Global developmental delay

significant delay across developmental domains

- gross motor, vision, fine motor, communication, hearing, social skills, behavior / coping skills

Pervasive Developmental Delay (PDD)

group of disorders characterized by delays in development of socialization and communication skills

Dysmorphic Characteristics

- Microcephaly

- Macrocephaly

- Misshapen skull

- Abnormal hairline

- Wide- or close-set eyes

- Cataracts

- Cleft palate

- Low, broad nasal bridge

- Small or large mouth

- Small or large tongue

- Epicanthal folds (skin fold of upper eyelid)

- Low-set ears

- Pectus excavatum ('hollowed chest')

- Pectus carinatum (protrusion of the sternum and ribs)

- Short limbs (brachymelia)

- Short digits (brachydactyly)

- Syndactyly (webbed hands/feet)

- Triphalangeal thumb

- Polydactyly (extra digits)

Down Syndrome

extra copy of chromosome 21

- extra chromosome 21 is contributed by the mother in 90% to 95% of children with this

What is a strong risk factor for down syndrome

maternal age

Trisomy or Nondisjunction Down Syndrome

extra 21st chromosome is replicated in every cell in the body

- cause of 95% of all DS cases

Translocation Down Syndrome

part of the 21st chromosome breaks off during cell division and attaches itself to another chromosome

- happens during or immediately after conception

- accounts for only 3-4% of DS cases

- in about one-third of translocation cases, one parent is a translocated chromosome carrier

Mosaicism Down Syndrome

rare form of DS, accounting for only 1-2% of all cases

- nondisjunction of the 21st chromosome takes place in one of the initial cell divisions after fertilization

- creates a mixture of 2 types of cells, some with 46 chromosomes and some with 47

Phenotypic Features in Down Syndrome

• Mild microcephaly

• Flat facial profile

• Low nasal ridge

• Upward slanted eyes

• Epicanthal folds

• Single mid palmer crease and short fingers

• Wide space between the big toe and second toe

• Flat foot

• Short stature

• Hypotonia

• Mouth may stay open with tongue sticking out

• Shortened palate

• Joint hypermobility

• Intellectual disability

• Developmental delay

• Delayed motor milestones

• Myopia

What does down syndrome cause a higher incidence of?

hearing, endocrine, developmental, dental, musculoskeletal, and neurological conditions

Compared to children without down syndrome, children with down syndrome are at higher risk for:

• Hearing loss (up to 75% may be affected)

• Obstructive sleep apnea (between 50-75%)

• Ear infections (between 50 -70% may be affected)

• Eye diseases, like cataracts (up to 60%)

• Eye issues requiring glasses (50%)

• Heart defects present at birth (50%)

• Intestinal blockage at birth requiring surgery (12%)

• Hip dislocation (6%)

• Thyroid disease (a problem with metabolism) (4-18%)

• Anemia (3%)

• Iron deficiency anemia (10%)

• Leukemia (1%) in infancy or early childhood

• Hirschsprung disease (<1%)

Atlantoaxial Instability

enlarged space between the first and second cervical vertebra (atlas and axis)

- identified by imaging between ages 3-5

- 1-2% will develop complication (risk of subluxation and spinal cord compression)

Precautions for Atlantoaxial Instability

• Avoid exercises that place excessive pressure on neck e.g. tumbling and excessive neck flexion or extension

• Parent education

• Avoid activities and sports with higher risk for neck compression e.g. boxing, diving, horseback riding, gymnastics and jumping on the trampoline should be avoided

• No activity restrictions if normal neck x-rays

Body Function and Structure Impairments with Down Syndrome

• Generalized low muscle tone

• Muscle weakness

• Slow postural reactions

• Joint laxity

• Intellectual impairments - varies among individuals with DS

• Flat feet features

• Pelvic hypoplasia with shallow acetabulum

• Cardiac anomalies

• Early onset of dementia is common

Potential Activity Limitations and Participation Restrictions with Down Syndrome

• Delay in achieving most gross and fine motor skills and language

• May need adaptations to participate in organized sports and active recreation activities

• May have difficulty maintaining sustained play with peers or family

PT Interventions for down syndrome

• Focus on attainment of developmental milestones

• Family education

• Gross motor skills

• ADLs

• Balance

• Mobility (ambulatory)

• Special education

• Lifelong focus on fitness

• Orthotics e.g. Supramalleolar Orthoses (SMO) to improve foot stability and gross motor skills (ages 3- 8)

Trisomy 18 - Edwards Syndrome

trisomy of 18th chromosome

- second most common trisomy

- over 100 associated malformations

- initial hypotonia, hypertonicity develops

Lifespan with Trisomy 18

90% born alive, die within the 1st year - medial age of survival is 2 weeks

- death due to aspiration pneumonia, congenital heart defects, increases susceptibility to infections and apnea

Cri Du Chat

deletion on chromosome 5

S&S of Cri Du Chat

• High pitched "cat-like" cry, due to abnormal laryngeal dev

• IQ in moderate to severe learning disability range

• Webbing between the fingers/toes

• Downward slant to the eyes

• Low birth weight and slow growth

• Low set ears, little

• Microcephaly

• Micrognathia (small jaw)

• Wide-set, downward slanted eyes

• Hypotonia

• Clumsy

• Hyperactivity

• Repetitive body movements

• Single crease (Simian crease) on palm

• Limitation in speech

• Limitation in most ADLs

18p Syndrome

deletion of the short arm of chromosome 18

- Subtle phenotypic features Min-mod growth deficits

- Hypotonia

- Mild microcephaly

- Epicanthal folds

- Motor performance is better than language function

- Variable degrees of cognitive impairment

Prader Willi Syndrome

disorder of chromosome 15

S&S of Prader Willi Syndrome

• Distinctive facial features: narrow face, almond shape eyes, small mouth with thin upper lip and down-turned corners

• Hypotonia

• Feeding problems and poor weight gain in infancy

• Excessive hunger and eating/obesity after infancy

• Big weight gain between one and six years of age, leading to morbid obesity

• Short stature

• Small hands and feet

• Thick saliva

• Mild to moderate cognitive impairment and learning disabilities

• Speech articulation problems

• Global developmental delay

• Hypogonadism

• Behavior problems like temper tantrums, violent

outbursts, OCD

• Sleep disorders, osteoporosis, scoliosis

Angelman Syndrome

• Inherited from mother

• Children may appear normal at birth

• Developmental delays by year 1

• Feeding problems

• "Happy puppet syndrome"

• Flat head

• Wide, smiling mouth, tongue may protrude

• Frequent bouts of laughter, not associated with happiness

• Seizures may develop

• Sleeping disorders

• Severe limitations in speech

• Characteristic arm position - arms held with flexed wrists and elbows

• Movement and balance disorders

• Ataxic gait

• Severe mobility limitations

• Severe limitations with ADLs

Fragile X Syndrome

Inherited from mother - mutation of a gene on the X Chromosome (dominant)

S&S of Fragile X Syndrome

• Decreased production of protein needed for brain dev

• Boys affected more severely than girls

• High palate

• Prominent ears

• Large head with prominent forehead

• Delayed motor milestones

• Hyptonia

• Flexible finger joints

• Flat feet

• During puberty boys usually develop large testicles and a long

face

• Moderate to borderline cognitive impairment/mental retardation

• ADHD common

• Autistic-like behaviors - hand biting or flapping

• Generally few restrictions in activities and participation related to motor skills (depends on level of cognitive impairment)

• Tactile defensiveness

Rhett syndrome

Sex linked disorder - Mutation of MECP2 gene located on the X chromosome (Dominant)

• Rarely inherited

• Occurs almost exclusively in girls

• Hypotonia

• Ataxia

• Characteristic trunk rocking, hand wringing, tapping or mouthing

• Severe cognitive impairment

• Significant limitations in all activities and participation

Triple X Syndrome / Trisomy X

Extra X chromosome

• 1 in 1,000 newborn girls

• Random mutation

• Often no unusual physical features or medical problems

• May be taller than average

• Increased risk of learning disabilities

• Delayed speech

• Developmental delays

• Behavioral problems- shyness, emotional immaturity

• Normal reproductive development

• Difficulty with gross motor skills - may be clumsy

Smith-Magenis Syndrome

Deletion mutation on chromosome 17

S&S Smith-Magenis Syndrome

• Facial features - brachycephaly (short wide head), prominent forehead, broad nasal bridge, prognathism (protruding jaw), and ear anomalies

• Infant feeding problems

• Variable levels of mental retardation

• Early speech/language delay

• Hoarse deep voice

• Middle ear problems

• Skeletal anomalies

• Decreased sensitivity to pain

• Chronic sleep disturbances

• Arm hugging/hand squeezing

• Hyperactivity and attention problems

• Prolonged tantrums, sudden mood changes

• and/or explosive outbursts and self-injurious behaviors

• Short stature

• Brachydactyly (short fingers and toes)

• Low muscle tone

• Developmental delay

William's Syndrome

Random genetic mutation - deletion of part of Chromosome 7

S&S of Williams Syndrome

• Individuals who have WS have a 50 percent chance of passing to children

• Unique personality that combines overfriendliness and high levels of empathy with anxiety

• Associated with elevated blood calcium levels in infancy

• Cardiovascular disease

• Developmental delay

• Mild to moderate intellectual disability, learning disabilities

• Associated with ADHD

• Puffiness around the eyes

• Some have star-like pattern in the iris of their eyes

• Short nose with a broad nasal tip

• Wide mouth, full cheeks, full lips, and a small chin.

• Elongated neck

• Depressed shoulder position/posture

• Short stature

• Advanced verbal skills

• Poor visual-spatial skills

• Limited mobility in joints

• Scoliosis

• By age 30, most have diabetes or pre-diabetes

• Mild to moderate hearing loss by age 30 due to disturbed function of the auditory nerve

• About 50% have anxiety and specific phobias