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
