TABLE 2.

Clinical features of six dual diagnosis patients

Patient case number	Organ system involved	Clinical features outside of 22q11.2 deletion syndrome and consistent with secondary diagnosis	Clinical features consistent with 22q11.2 deletion syndrome
1	Neurology/development	Cavum septum pellucidum; DEVELOPMENT Delayed milestones: sat 12 mo; walked 24 mo; speech 24 mo; Asperger’s syndrome; anxiety; 19 yo at 8th grade academic level; IEP; repeated one grade during schooling	Cavum septum pellucidum; sagittal synostosis; DEVELOPMENT Delayed milestones: sat 12 mo; walked 24 mo; speech 24 mo; Asperger’s syndrome; anxiety; 19 yo at 8th grade academic level; IEP; repeated one grade during schooling
	Otolaryngology	Anosmia (MRI: olfactory sulci hypoplastic; no visualization of well-formed olfactory bulbs); bilateral sensorineural hearing loss	Three otitis media infections in 12 mo, recurrent, monthly sinus infections; small mandible, narrow nasal valves bilaterally; bilateral sensorineural hearing loss
	Cardiology	Peripheral pulmonic stenosis	NR
	Ophthalmology	Coloboma involving optic nerve	Coloboma involving optic nerve
	Orthopedics	NR	Scoliosis
	Endocrinology	Amenorrhea, low follicle stimulating hormone (FSH)	Bone age at 19 yo was 13 yo (beyond 2SD)
	Gastrointestinal	Esophageal atresia; colonic interposition with surgical repair and gastrostomy tube placement; hospitalized multiple times for GI concerns	Esophageal atresia
	Genitourinary	Slight shortening of labia (underdeveloped) in neonatal period; diminutive uterus	NR
2	Neurology/development	NR	Deep sacral dimple, normal spine MRI; DEVELOPMENT: delayed crawling; walked at typical age; speech delay; Bayley Scale of Infant Development: general cognitive abilities avg to low avg; Vineland Adaptive Behavior Scales: avg to low avg adaptive behavioral skills; No concerns on Child Behavior Checklist. 23 mo old: development quotient 92 (avg range); receptive language skills at 18 mo level and emerging to the 19 to 24 mo level; Expressive language skills 13 to 18 mo level. At 5.5 yo attended regular school for kindergarten but in a special classroom with IEP. Received PT briefly
	Otolaryngology	NR	Chronic otitis media infections and persistent nasal regurgitation with emesis; possible subglottic cyst on laryngoscopy and a bifid uvula; mild low-frequency conductive hearing loss in the right ear and abnormal results in the left ear due to excessive cerumen; right tympanic membrane perforation and left myringotomy; hypernasal speech with glottal stops
	Cardiology	NR	Ventricular septal defect (VSD) (with concern for aortic arch hypoplasia)
	Ophthalmology	NR	Bilateral esotropia without his glasses
	Orthopedics	NR	Toes: two overlapping three bilaterally, long, slender fingers with bilateral transitional palmar creases; extra rib and hyperextensibility
	Immunology	NR	Significant immune deficiency: inadequate responses to vaccines; 3 yo with normal B and T-cell subsets, normal immunoglobulin levels, and normal lymphocyte stimulation assay, except for low-normal candida response: cleared to receive live vaccines
	Pulmonology	MRSA pneumonia; bronchomalacia, minimal membranous subglottic stenosis; increased airway secretions; chest CT with diffuse mosaicism of the lung without obvious bronchiectasis, recurrent pneumonia	NR
	Endocrinology	Vitamin D deficiency	Hypocalcemia following VSD repair
	Gastrointestinal	Failure to thrive requiring overnight G-tube feeds; constipation without distal intestinal obstruction syndrome; elevated liver function studies at 5yo	Failure to thrive requiring overnight G-tube feeds; constipation; gastroesophageal reflux disease
	Nephrology	NR	Renal calculi seen on ultrasound at 5yo
3	Neurology/development	DEVELOPMENT significant delays: sat 12 mo; walked 22–25 mo, severe mixed receptive and expressive language disorder (at 28 mo had 20 words; at 3 yo 4 mo total language score of 11 mo equivalent (expressive 1 yo 1 mo and comprehension 11 mo); Autism spectrum disorder; not toilet trained at 3 yo. At 4 yo 3 mo: fine motor 9–12 mo for pincer grasp, other skills at 6 mo level; OT noted impaired strength, muscle tone, coordination, cognition and acquisition of milestones; developmental pediatrician was concerned for ID at his 4 yo visit based on skills assessed at <1 yo	Sacral dimple, pilonidal cyst and a tethered cord (slightly low position of the conus terminating at upper L3 level); two regions of fatty infiltration in the filum terminale noted
	Otolaryngology	NR	Sensitivity to noise; normal audiogram at 25 mo old; one ear infection between 12 and 24 mo old
	Ophthalmology	NR	Esophoria and moderate hyperopia with no need for corrective lenses
	Immunology	NR	NR; T cells unaffected
	Pulmonology	NR	Mild intermittent asthma well controlled on albuterol
	Endocrinology	HbA1C normal; short stature; growth hormone response to stimulation: borderline deficient	Short stature; growth hormone response to stimulation: borderline deficient
	Gastrointestinal	NR	Constipation; poor weight gain; frequent reflux leading to cough, treated with ranitidine
	Nephrology	Multicystic dysplastic kidney (prenatal onset), and no obstruction on the left but with compensatory hypertrophy in the left kidney and normal kidney function; elevated spot urine oxalate:creatinine ratios, but urine hyperoxaluria panel was normal; normal creatinine and PTH levels	Multicystic dysplastic kidney; 2 mo old: small nonobstructing stones in left kidney
	Urology	Cryptorchidism; 3 yo: moderate atrophy of the right testis and a normal left testis with compensatory hypertrophy	NR
	Hematology	NR	Thrombocytopenia in newborn period; anemia at 2 mo
4	Neurology/development	NR	At 9 yo, taking risperidone; difficulty expressing emotions and opening up to discuss his worries; intermittent headaches with vomiting; benign developmental venous anomaly in the left cerebellum with associated signal abnormality; no associated cavernoma. Benign developmental venous anomaly in the left frontal lobe. Probable synovial cyst with hemorrhage fluid level between the dens and left lateral mass of C1; DEVELOPMENT: rolled over 6 mo; sat/crawled 9 mo; pulled to stand 12 mo; ran/hopped/walked 2 yo; climbed stairs 3 yo; first words 12 mo; sentences 2 yo; toilet trained 2 yo; Autism spectrum disorder; mixed receptive-expressive language disorder; 13 yo attends 7th grade at a public school in full time autism support placement, with no aide in school; reads at a 4th–5th grade level and does well with basic math; previously received PT/OT/speech
	Otolaryngology	NR	Normal hearing assessment
	Cardiology	NR	Normal echocardiogram with some question of an additional vessel; unlikely vascular ring
	Ophthalmology	NR	Corrective lenses
	Orthopedics	NR	Scoliosis; pectus excavatum; pes planus bilaterally with tight heel cords and hamstrings; head tilt; very long slender fingers, sandal gap of his toes
	Immunology	NR	Normal immunology testing
	Pulmonology	NR	Past history of asthma now resolved
	Endocrinology	NR	Slightly high T4 levels with normal thyroid stimulating hormone
	Gastrointestinal	NR	Weight low for height percentile at 13 yo; sporadic and intermittent emesis since age 10 yo thought to be abdominal migraines
	Hematology	Glucose-6-phosphate dehydrogenase deficiency	NR
5	Neurology/development	NR	Seizures from 18 mo to 5 yo 6 mo; anxiety, bipolar disorder, social anxiety, delusional thinking and psychosis. He had symptoms of hyperactivity and aggressive behaviors; headaches; insomnia, past history of night terrors; hospitalized once for an episode of mania with psychotic features; DEVELOPMENT: walked 18 mo; first words 2 yo 6 mo; hypernasal speech, IEP, PT/OT/speech therapies in childhood, ADHD, social anxiety; full scale IQ 78; 17 yo: completing high school and obtaining GED
	Otolaryngology	NR	Frequent otitis media and myringotomies, tympanostomy and adenoidectomy; velopharyngeal insufficiency
	Cardiology	NR	VSD and interrupted aortic arch; developed a subaortic web; patching of the supravalvular region to relieve supravalvular aortic stenosis at the site of the aortotomy from the original surgery; cardiac MRI showed mild residual subaortic obstruction as well as mild stenosis of the left subclavian artery
	Orthopedics	NR	Normal C spine films
	Immunology	NR	Low T-cell count at around 4 yo; history of chronic rhinitis and chronic sinus infections
	Pulmonology	NR	Obstructive sleep apnea due to narrow palate; asthma
	Endocrinology	NR	Hypocalcemia and hypothyroidism
	Gastrointestinal	NR	Constipation; chronic, recurrent, crampy abdominal pain since age 3 yo; feeding difficulties and failure to thrive in infancy
	Urology	NR	Inguinal hernia; hydrocele and phimosis
	Nephrology	NR	Cystic right kidney on renal ultrasound (small simple cyst)
	Hematology	Excessive bruising and a prolonged partial thromboplastin time of 42 s; low level of ristocetin cofactor activity 40% (normal 46% to 150%): consistent with the diagnosis of mild type 1 von Willebrand disease	NR
6	Neurology/development	Microcephaly; DEVELOPMENT: rolled over 7mo, sat 9 mo, walked 20 mo, single words 2.5 yo, short sentences 3 yo, difficulty toilet training	Low muscle tone; microcephaly, DEVELOPMENT: rolled over 7 mo, sat 9 mo, walked 20 mo, single words 2.5 yo, short sentences 3 yo, difficulty toilet training
	Otolaryngology	NR	Otitis media, aspiration, laryngeal cleft type I, nasopharyngeal reflux, velopharyngeal insufficiency and hypernasal speech
	Orthopedics	Congenital scoliosis and mild kyphosis; anterior arch C1 hypoplasia, increased atlantodental interval with flexion, lumbar butterfly vertebra, and vertebral fusion anomalies	Congenital scoliosis and mild kyphosis; anterior arch C1 hypoplasia, increased atlantodental interval with flexion, lumbar butterfly vertebra, and vertebral fusion anomalies
	Immunology	NR	Frequent upper respiratory infections, low IgM, and nonprotective pneumococcal titers, moderate CD8 T-cell lymphopenia
	Endocrinology	NR	Short stature
	Gastrointestinal	NR	Dysphagia, feeding difficulties, reflux, vomiting, constipation, failure to thrive, gastrostomy tube dependent

Abbreviations (mo = months old; yo = years old; IEP = individualized education plan; NR = none reported; avg = average; PT = physical therapy; ID = intellectual disability; OT = occupational therapy; ADHD = attention deficit and hyperactivity disorder; italics = overlapping features.