1. Head, Eyes, Ears, Nose, Throat |
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- Children and Adults: 15% have strabismus in addition to other ocular issues (e.g., cataracts, retinal problems)
- Conductive and/or sensorineural hearing loss (often unilateral) occur in 45% and 10% respectively
- Most have chronic otitis media
- 69% have palatial abnormalities, particularly velopharyngeal insufficiency (VPI) that is often associated with hyper-nasal speech, some of whom have submucosal cleft palate, and a small minority have overt cleft palate, which can lead to nasal regurgitation
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- Refer to an ophthalmologist for assessment at diagnosis and during preschool years
- Refer to an audiologist for evaluation in infancy (or when diagnosed) and every 6 months up to 8 years of age, then annually until adulthood
- Often need regular ear cleaning to remove cerumen
- Examine the palate in infancy and evaluate for feeding problems and/or nasal regurgitation and, if warranted by clinical findings, refer to a cleft palate team
- Refer to a speech and language pathologist for assessment by 1 year of age, sooner if warranted or when diagnosis is made
- Evaluate nasal speech quality
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2. Dental |
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- Children and Adults: Retrognathia (over-bite) is common and may cause dental malocclusion
- Significant dental issues are a recognized part of the syndrome (e.g., enamel hypoplasia and chronic caries)
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- Refer to a dentist in early childhood
- Advocate and ensure for appropriate dental care
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3. Cardiovascular |
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- Children and Adults: Between 40% and 74% have congenital heart defects, most commonly of the conotruncal type (e.g., Tetralogy of Fallot, interrupted aortic arch, ventricular septal defect)
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- At the time of diagnosis, complete a cardiovascular assessment, including EKG and echocardiogram
- Refer to a cardiologist as warranted by clinical findings
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4. Respiratory |
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- Children: Congenital malformations may lead to upper and/or lower airway obstructions
- Most airway concerns resolve spontaneously with time but some require surgical intervention (e.g., Robin sequence)
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- Refer to an ENT surgeon for evaluation as warranted by clinical findings
- Consider a pre-op anesthesia consultation regarding narrow airways prior to the first surgery
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- Adults: In order of prevalence, there is an increased frequency of recurrent pneumonia, atelectasis, asthma, and chronic obstructive pulmonary disease
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- Consider periodic pulmonary function studies and referral to a pulmonologist as warranted by clinical findings
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5. Sleep |
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- Children: Congenital malformations may lead to airway obstructions and obstructive sleep apnea (OSA)
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- Undertake a sleep study in infancy and then as warranted by clinical findings after 3 years of age
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- Adults: Those with uncorrected congenital malformations remain at risk for OSA
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- Undertake a sleep study as warranted by clinical findings
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6. Gastrointestinal |
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- Children and Adults: Feeding difficulties, related to pharyngeal and gastrointestinal tract hypotonia, commonly lead to failure to thrive
- Dysphagia and constipation, with or without gastrointestinal structural anomalies, are common
- Gastroesophageal reflux also is common
- 20% develop gallstones
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- Refer to a gastroenterologist and feeding specialist (e.g., speech-language pathologist)
- Treat constipation
- If difficulty swallowing pills, adapt medication regime (e.g., provide with liquid medication, crush pills)
- If there are unexplained gastro-intestinal findings or changes in behavior or weight, investigate for constipation, GERD, peptic ulcer disease, and pica.
- Screen annually for manifestations of GERD and manage accordingly. If introducing medications that can aggravate GERD, monitor more frequently for related symptoms.
- Consider obtaining an abdominal ultrasound in adults to assess for gallstones
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7. Genitourinary |
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- Children and Adults: Up to 33% may have renal tract anomalies
- 10% may develop renal failure in adulthood
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- Undertake a renal ultrasound at the time of diagnosis
- Maintain surveillance for urinary tract infections (UTIs)
- Determine creatinine levels at diagnosis and annually thereafter
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8. Sexual function |
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- Children and Adults: People with the 22q11.2 deletion syndrome are fertile and have a 50% chance of transmitting the 22q11.2 deletion to children
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- Referral for genetic counseling may be appropriate
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9. Musculoskeletal |
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- Children and Adults: Many have skeletal abnormalities, most commonly vertebral or rib anomalies
- A minority have short stature during childhood that improves by adulthood
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- Undertake cervical spine X-rays after age 4 years to assess for vertebral anomalies and instability on flexion/extension (five views: flexion, extension, AP, lateral, and open mouth)
- Arrange chest X-ray to evaluate for thoracic vertebral anomalies
- Provide clinical evaluation for scoliosis at diagnosis, during preschool, and periodically thereafter
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10. Neurological |
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- Children and Adults: Impairments due to reduced muscle tone and motor delay are common in children
- Seizures are frequently associated with hypocalcemia
- 40% of adults have recurrent (often hypocalcemic) seizures
- Cord compression may occur related to skeletal anomalies
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- Undertake a neuro-developmental assessment of infants with particular attention to reduced muscle tone and motor delay
- Refer to a physical therapist (PT) and/or occupational therapist (OT), as needed
- Ascertain history with attention to seizures
- Consider checking serum ionized calcium following any seizure activity
- Include EEG examination in evaluation if indicated
- Symptoms of cord compression are an indication for an emergent referral to a neurologist or neurosurgeon
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11. Behavioral / mental health |
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- Children and Adults: Conditions such as autism spectrum disorder (ASD), attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD) are common
- Treatable anxiety disorders and depression are common
- Behavioral differences may begin at a young age
- 60% of adults have a psychiatric disorder
- Schizophrenia can become apparent in adolescence and 25% develop schizophrenia or other psychotic disorders in adulthood
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- Ascertain comprehensive behavioral and mental health history
- Refer to a psychiatrist if evidence of ASD, ADD, ADHD, or OCD occurs
- Screening children for psychiatric issues before age 10 years may provide an opportunity for early intervention
- Assess for psychiatric illness with attention to changes in behavior, emotional state and thinking, including hallucinations or delusions and at-risk behaviors (e.g., sexual activity, alcohol/drug use) in teens and adults
- Refer to a psychiatrist as warranted by clinical findings
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12. Endocrine |
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- Children & Adults: 60% have episodic hypocalcemia (often missed when mild or transient)
- Hypocalcemia is due to hypoparathyroidism in children and adults
- Long-term calcium supplementation can lead to renal calculi
- Hypo- and hyperthyroidism have been reported in children and adults
~ 4% have growth hormone deficiency
~ 35% of adults are obese
~ 20% of adults have hypothyroidism
~ 5% of adults have hyperthyroidism
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- Measure serum ionized calcium concentration in neonates, then annually to assess for hypoparathyroidism
- Assess calcium levels in infancy, every 3 to 6 months, every 5 years through childhood, and every 1 to 2 years thereafter
- Be vigilant regarding risk of hypocalcemia with acute illness and childbirth
- All patients should have vitamin D supplementation; those with documented hypocalcemia and/or relative or absolute hypoparathyroidism may require prescribed hormonal forms supervised by endocrinologist
- Refer to an endocrinologist as warranted by clinical and laboratory findings and for initial management of hypocalcemia
- Consider densitometry to assess for osteopenia earlier than in general population
- Undertake T4 and TSH baseline screening2
- Treat with standard thyroid replacement or antithyroid therapy where warranted2
- Monitor growth and growth hormone levels annually and consider endocrinology assessment for poor growth
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13. Hematological |
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- Children and Adults: Autoimmune diseases (e.g., thrombocytopenia, juvenile rheumatoid arthritis, Grave’s disease, vitiligo, neutropenia, hemolytic anemia) may be more common than in the general population
- 10% develop splenomegaly
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- Monitor with CBC; thyroid function annually or if concerns arise
- Investigate arthritis problems for juvenile rheumatoid arthritis and refer to a rheumatologist as warranted
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14. Infectious disease/immunization |
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- Children and Adults: Congenital thymic aplasia is recognizable in infancy3
- 77% have immune deficiency (although thymic aplasia is rare, thymic hypoplasia is common); improvement in T-cell production may occur over time
- 75% have chronic otitis media and frequent respiratory infections
- Irradiated blood products have been used when blood replacement has been necessary
- Recurrent upper and lower respiratory tract infections are common in adults
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- In addition to obtaining a CBC with differential in newborns, consider undertaking flow cytometry.
- For infants, minimize exposure to infectious diseases and withhold live vaccines initially. Refer infants to an infectious disease specialist to assess regarding influenza vaccines, CMV-negative irradiated blood products and RSV prophylaxis
- Measure absolute lymphocyte count following initial diagnosis and refer to an immunologist if count is lowAt age 9 to 12 months (prior to live vaccines), assess flow cytometry, immunoglobulins and T-cell function
- Evaluate immune status before offering any live vaccines
- Treat respiratory and other infections aggressively in children and adults
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15. Dermatological |
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- Children and Adults: 35% have seborrhea or dermatitis
- 25% have severe acne
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- Examine skin as part of routine care
- Treat as per general population, with referral to dermatologist as needed
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16. Other |
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- Incidence: 1/4000, but more likely higher and many without typical features
- Huge variability in level of developmental disability and the number and severity of associated features
- IQ: The majority of affected people with 22q11 deletion fall in the high mild to borderline range; moderate to severe rates and average levels of IQ are less common
- A selection bias in reported studies may result in over-estimating some prevalence rates
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