Genetics- AAP Health Surveillance Flashcards
Trisomy 21 - Physical Features (list as many as you can!)
- hypotonia
- small brachycephalic head
- epicanthal folds
- flat nasal bridge
- upward-slanting palpebral fissures
- Brushfield spots
- small mouth
- small ears
- excessive skin at the nape of the neck
- single transverse palmar crease
- short fifth finger with clinodactyly
- wide spacing between the first and second toes, often with a deep plantar groove
Trisomy 21- Associated Medical Issues?
- Hearing problems (75 %)
- Vision problems (60–80%)
Nystagmus (3–33)
Glaucoma (<1–7)
Nasolacrimal duct occlusion 3–36
Strabismus (36)
Cataracts (3)
Refractive errors (36–80) - Obstructive sleep apnea (50–79)
- Otitis media (50–70)
- Congenital heart disease (40–50)
AVSD - Feeding difficulty 31–80
- Respiratory infection 20–36
- Dermatologic problems 56
- Hypodontia 23
- Congenital hypothyroidism 2–7
- Duodenal atresias 12
- Transient abnormal myelopoiesis 10
Leukemia 1 - Autoimmune conditions
Hashimoto thyroiditis 13–39
Graves’ disease 1
Celiac disease 1–5
Type 1 diabetes 1
Juvenile idiopathic arthritis <1
Alopecia 5 - Symptomatic atlantoaxial instability (1–2)
- Autism (7–19)
- Hirschsprung disease (1)
What is the risk that parents with a first child who has T21 will have another baby with T21?
∼96% of the time the condition is sporadic because of nonfamilial trisomy 21, in which there are 47 chromosomes with the presence of a free extra chromosome 21. Recurrence risk = 1% under 40yrs
In ∼3% to 4% of cases, the extra chromosomal material is the result of an unbalanced translocation between chromosome 21 and another chromosome, usually chromosome 14 or 21. Approximately 3/4 of these unbalanced translocations are de novo, and 1/4 result from translocation inherited from a parent. If the child has a translocation, the parents should be offered a karyotype to determine whether the translocation is familial or de novo. If inherited from Mom, 10-15% recurrence risk. If inherited from Dad 2-5% recurrence risk.
IF either parent has a 21/21 translocation -> 100% recurrence risk
Diagnostic test for T21?
Karyotype (FISH can be done for more rapid results but should be confirmed by Karyotype)
T21- Evaluation at birth?
- Echo
- Feeding safety (poor tone can impair feeding)
- Red reflex (for cataracts)
- Hearing screen
- Passage of mec (Hirschprungs)
- CBC in first 3 days of life to assess for transient abnormal myelopoiesis and polycythemia
- TSH (should be on newborn screen)
Health Surveillance for T21:
TSH at 6mo, 1yr and then q1yrly
CBC 0,6mo, 1yr then q1yrly (+iron studies)
Hearing 0, 6mo, then q1yrly
Screen vision at each appointment
Discuss symptoms of atlantoaxial instability (change in gait, change in bowel or bladder function, neck pain, stiff neck, head tilt, torticollis, weakness) cervical spine XR only if symptoms
Screen for symptoms of OSA, obtain PSG between 3-7yrs
Screen for symptoms of celiac - TTG if symptoms present
Turners Syndrome- Diagnostic Test?
Karyotype 45 X
Turners Syndrome - Physical features?
- High-arched palate
- Low posterior hairline
- Broad short-appearing neck
- Pterygium colli (webbed neck)
- Broad chest (shield chest)
- Lymphedema of hands and feet
- Cubitus valgus
- Short fourth metacarpal
- Madelung deformity
- Neurocognitive and psychosocial issues
Turners Syndrome - Associated Medical Issues?
- Growth failure
- FTT 50
- Endocrinopathies
Glucose intolerance 15–50
Type 2 diabetes 10
Thyroid 15–30
Hypertension 50 - Gastrointestinal and hepatic disorders
Elevated hepatic enzymes 50–80
Celiac disease 8
Inflammatory bowel disease 2–3
-Eyes
Nearsightedness 20
Strabismus 15
-Ears
Infection of middle ear 60
Hearing defects 30
Deformity of external ear 15 - Bone age delay 85
- Scoliosis 10
- Bicuspid aortic valve 14–34
- Coarctation of the aorta 7–14
- Horseshoe kidney 10
- Abnormal positioning or duplication of renal pelvis, ureters or vessels 15
Turners Syndrome - Health Surveillance:
TSH - at diagnosis then q1yrly
Renal US- at diagnosis
Echo- at diagnosis
Hearing - q5yrs starting at diagnosis
Vision- at 12-18mo or at time of diagnosis
Celiac screen q2-3yrs until age 10
GH treatment early (around 4–6 years of age)
Puberty: estrogen replacement should start between 11 and 12 years of age increasing to adult dosing over 2–3 years
HbA1c- annually starting at age 10
LFTs- annually starting at age 10
NF Diagnostic Criteria
Diagnostic Criteria: at least 2/7:
6 or more Café-au-lait macules (> 5mm pre-pubertal, > 15mm post-pubertal)
> 2 neurofibromas (nerve sheath tumours) OR 1 plexiform neurofibroma (arise from 1 or multiple nerve trunks/branches)
Axillary or inguinal freckling (usually starts around 3 to 5 yo)
Optic glioma
> 2 or more Lisch nodules
A distinctive osseous lesion (sphenoid dysplasia or tibial pseudoarthrosis or severe kyphoscoliosis)
Affected 1st degree relative
Indications for considering neuroimaging in NF-1?
- Focal sensory or motor symptoms
- New onset of seizures
- Headaches that are increasing in frequency or severity
- Signs of increased intracranial pressure (headaches, visual disturbance, increased lethargy)
- Transient ischemic attack or stroke-like symptoms
- Decline in visual acuity or visual fields
- Precocious puberty or accelerated growth
- Head and neck plexiform neurofibromas increasing in size or with new development of pain
- Encephalopathy or cognitive deterioration
- Extremity asymmetry (ie, leg-length discrepancy)
NF1- Health Surveillance
Yearly optho
Yearly BP
Yearly scoliosis screening
Yearly skin exam
Noonan Syndrome - Physical Features?
- Low-set, posteriorly rotated ears
- Widely spaced and downslanted palpebral fissures
- Epicanthal folds
- Ptosis
- Short stature
- Broad or webbed neck
- Shield chest
- Widely spaced nipples
- Cryptorchidism in boys
- Lymphedema of the hands and feet
Noonan Syndrome - Associated Medical Issues
Eye anomalies 95%
- strabismus and refractive errors
Short stature 50%-70%
Hypotonia Majority
Pectus anomaly Majority
Cryptorchidism in males 60%-80%
Congenital heart disease 50%-80% - most commonly pulmonary valve stenosis, hypertrophic cardiomyopathy
Hearing loss 40%
Learning disability 25%
Renal anomalies 11%
- Most commonly dilatation of the renal pelvis
Abnormal bleeding or bruising
Juvenile myelomonocytic leukemia (JMML)
Increased risk of AML, ALL, Neuroblastoma
Chiari malformation
Noonans - Health Surveillance:
Echo at diagnosis, then q1yr until 5, then q5yrs
Optho annually
Hearing annually
Renal US at diagnosis
CBC at 1yr + prior to surgical procedure (bc of risk of bleeding diathesis)
Consider XR for scoliosis
Noonans- Inheritance?
AD (though most are de novo)
Williams - Physical Features?
- broad forehead
- bitemporal narrowness
- periorbital fullness
- a stellate and/or lacy iris pattern
- a short nose with a bulbous nasal tip
- a wide mouth
- full lips
- mild micrognathia
- Young children typically have small, widely spaced teeth; dental malocclusion
Williams - Associated Medical Issues?
Ocular and visual
Esotropia 50
Auditory
Recurrent otitis media
Hypersensitivity to sound
Progressive SNHL 65
Dental
Malocclusion 85
Microdontia 95
Cardiovascular
SVAS 75
SVPS 25
PPS 50
VSD 10
Hypertension 50
Prolonged QTc 13
Genitourinary
Structural anomaly 5
Enuresis 50
Nephrocalcinosis <5
Gastrointestinal
Feeding difficulties 70
Constipation 50
Rectal prolapse
Integument
Soft, lax skin 90
Inguinal hernia 40
Umbilical hernia 50
Musculoskeletal
Joint hypermobility
Joint contractures 50
Radioulnar synostosis 20
Calcium
Hypercalcemia 15–40
Hypercalciuria 30
Endocrine
Hypothyroidism 5–10
Early puberty 20
Neurologic
Chiari I malformation 10
Hypotonia (central) 80
Developmental delay 95
Behavioral
ADHD 65
Anxiety 70
Williams - Health Surveillance
Serum calcium every 4 to 6 months until 2 years of age, then q2yrs
Urine calcium/creatinine ratio at the time of diagnosis and if hypercalcemia is present on screening
Urinalysis yearly
Echo at diagnosis, yearly until age 5 then q2yrly
ECG yearly
Renal US at diagnosis
BP at every visit
Optho at diagnosis, then vision screening yearly
Hearing between 6 and 12 months of age and then q1yrly
TSH at diagnosis, annually for the first 3 years, and then q2yrly
Prader Willi - Physical Features:
- Severe neonatal hypotonia
- Short stature
- Failure to thrive in infancy
- Central obesity in childhood w/hyperphagia
- Almond-shaped eyes
- Strabismus
- Nystagmus
- Up-slanting palpebral fissures
- Thin upper lip
- Vision issues (Hyperopia or Myopia)
- Small penis
- Cryptorchidism
- Hypoplastic labia minora
- Small hands and feet
- Poor motor skills
- GDD
Prader Willi- Associated Medical Issues?
Hypoventilation
Obstructive sleep apnea
Central sleep apnea
Gastrointestinal
Feeding problems in infancy
Gastroesophageal reflux
Osteoporosis
Endocrine
- Hyperinsulinemia
- GH deficiency
- Hypogonadotropic hypogonadism
- Diabetes mellitus (type 2)
Psych issues
Prader WIlli - Health Surveillance:
- Annual hearing/vision screen < 3y
- Optho assessment at age 2-3
- May need more frequent dental visits (caries)
- Thyroid screen Q2-3 yrs starting at age 5, or if symptomatic
- Screen for OSA qvisit
- Consider GH treatment (need PSG before starting treatment)
Beckwith-Wiedemann Syndrome - Features?
- macroglossia
- hemihyperplasia
- omphalocele
- neonatal hypoglycemia (hyperinsulinemic)
- macrosomia
- HSM
- Cardiomegaly
- Kidney abnormalities (e.g., medullary dysplasia, nephrocalcinosis, and medullary sponge kidney)
- embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma)
- ear creases / posterior helical ear pits
BWS - Health Surveillance?
Screen for embryonal tumours:
AFP (for hepatoblastoma) & abdo US q3mo until 4yo
Then renal US including adrenal glands q3mo until 8yo (then less frequently)
Periodic CXR and urine HVA/VMA (for neuroblastoma) have been suggested but low yield so not in most screening protocols
Consider measuring urinary Ca/Cr ratio annually
ECG & echo prior to surgical procedure
Russell-Silver Syndrome - Features?
- Small for gestational age (asymmetric SGA)
- FTT
- Relative macrocephaly
- triangular face
- fifth finger clinodactyly
- Feeding difficulties
- Micrognathia with narrow chin
- Hypoglycemia
- Cafe au lait macules
Russell-Silver Syndrome - Health Surveillance?
Monitoring of ketones and BG for ketotic hypoglycemia when ill, when decreasing frequency of feeds, or with increased physical activity
Assess for limb length discrepancy at all visits
Examine for scoliosis
Monitor for early puberty, adrenarche
DiGeorge Facial Features?
- hooded eyelids
- ear anomalies (small and low set)
- prominent nasal bridge
- bulbous nose
- micrognathia
- asymmetric crying facies
- craniosynostosis
- short and flat philtrum
DiGeorge Syndrome - Associated Medical Issues?
CHD: conotruncal defects (e.g., ventricular septal defect, tetralogy of Fallot, interrupted aortic arch, truncus arteriosus)
Palatal abnormalities: bifid uvula, cleft palate, and hypernasal speech, dysphagia
Laryngotracheoesophageal abnormalities: laryngotracheomalacia, and subglottic stenosis
Gastrointestinal anomalies: prone to hernias
Immune deficiency: thymic hypoplasia
Autoimmune disorders (e.g., juvenile rheumatoid arthritis, Grave’s disease, vitiligo)
Ophtho: coloboma, cataract, anophthalmia, and strabismus
SNHL
Hypocalcemia
Developmental delay
Psych
Skeletal anomalies: occipital-cervical anomaly, scoliosis, rib and vertebral anomalies, clubfoot, and polydactyly
Renal/GU: hydronephrosis, renal agenesis, multicystic/dysplastic kidney, cryptorchidism, and hypospadias
DiGeorge Syndrome - Health Surveillance?
Clinical tests @ diagnosis:
CBC
Serum calcium
PTH
TSH
T/B cell subsets
Ig’s (+ Post vaccine titres if older)
ECG + Echo
Renal US
Optho
Hearing
Calcium: Should be monitored Q3-6 months in first year, then every 5 years through childhood
TSH: Annually
CBC/Diff: Annually
Immunologic work-up: Flow cytometry at birth, then flow cytometry/immunoglobulins/T-cell function at age 9 to 12 months prior to live vaccines
C spine x ray once >4yrs old
VACTERL
Diagnostic: > 3 anomalies
Vertebral defects (hemivertebrae, butterfly, rib anomalies, sacral agenesis, scoliosis, tethered cord)
Anal atresia (others: imperforate anus, fistula)
Cardiac anomalies (VSD, ASD, TOF)
TEF
Esophageal atresia
Renal anomalies (renal agenesis/dysplasia, horseshoe kidney, ureteral anomalies)
Limb (radial defects): underdevelopment/agenesis of thumb, radial bone
VACTERL workup?
XR spine, pelvis and chest
Attempt to pass NG tube (TEF)
ECG and Echo
Renal US
Marfan Syndrome - Health Surveillence?
Echo at diagnosis then annually
Optho at diagnosis then annually
Monitor for scoliosis/joint deformities/pectus deformities annually (1-5yrs) then Q6months (6-18yrs)
Bone age once between 6-12yrs
Sports:
Avoid isometric or burst exertion activities (weight lifting, press-ups, sprinting) because strain on heart
Highest risk sports include: basketball, lifting/body building, hockey, running, skiing, racquet ball, surfing, scuba diving, rock climbing
Contact sports contraindicated for risk retinal detachment (ex. Boxing, karate)
Fragile X - Clinical Features?
- prominent forehead
- a long, narrow face
- a prominent jaw
- protuberant ears
- high arched palate
- large testes
Fragile X- Health Surveillence:
Audiology: yearly (60-80% have recurrent OAM causing hearing loss)
Optho at 1yr (for strabismus and refractive errors)
Supportive: SLP if needed, behavioural interventions, medications for ADHD, anxiety, etc.
Dental: can have dental crowding
Screen for joint laxity at each visit
Features of Achondroplasia
Short stature
Limb shortening
Trident hand
Frontal bossing
Midface hypoplasia
Macrocephaly
Normal cognition
Achondroplasia- Associated Medical issues?
- lower extremity long bone bowing
- middle-ear dysfunction
- obstructive sleep apnea
- cervicomedullary compression
- hydrocephalus
- thoracolumbar kyphosis
- central sleep apnea
Achondroplasia- Health Surveillance:
Birth - 1 mo:
- PSG & neuroimaging BEFORE DISCHARGE HOME
- Radiographs looking for classic features (skull, cervical spine, chest, abdomen with pelvis and upper female, lower extremity long bones, hands/feet), +/- molecular gene testing
Hearing yearly
Tuberous Sclerosis- Health Surveillance?
- Brain MRI every 1-3 yr
- Renal imaging using ultrasound, CT or MRI every 1-3 yr
- Echocardiogram every 1-3 yr in patients with cardiac rhabdomyomas, electrocardiogram every 3-5 yr in all.
- Optho yearly
- Dental examination twice a year
- Skin examinations once a year
Duchenne Muscular Dystrophy - Health Surveillance?
Neurology
Steroid treatment—monitor for complications of steroids
Bone density scan
Muscle strength testing
Orthopedics
Monitor for scoliosis, Achilles tightening
Manage fractures from falls
Cardiology: monitor for DCM – Echo q2y under age 10, yearly when >10y; ECG
Physiotherapy: passive stretching, night splints, chest PT
Respirology: PFTs, PCO2; monitor for nocturnal hypoventilation and provide ventilator assistance (BiPAP, CPAP) when needed
