Skip to main content
. 2018 Oct 8;21(5):1121–1130. doi: 10.1038/s41436-018-0295-y

Table 2.

Summary of clinically relevant CNVs

ID Chromosome Event Pertinent patient phenotypesa
P1b Xq11.2 55 kb de novo loss including first three exons of ZC4H2 Arthrogryposis, limited mobility of the proximal muscles of the shoulders and lower extremities, spastic paraparesis, abnormal myelination on MRI, bilateral ulnar deviation and shortened deformed fingers, reactive airway disease, dysarthria, and global developmental delay
P2b 22q11.21 434 kb de novo gain

History of multiple bone fractures, hypotonia, delayed motor skills, strabismus, hypermobility, flat feet, and joint pain

Note: In addition to the CNV identified, a missense variant in WNT1 was identified providing an explanation for bone fragility and other associated phenotypes

P3bc Xq13.1 9 kb de novo loss encompassing exon 11 of HDAC8 Delayed motor milestones, hypotonia, intrauterine and postnatal growth retardation, and dysmorphic features suggestive of Cornelia de Lange syndrome
P4b 2p11.2 228 kb maternally inherited gain encompassing REEP1

Demyelinating disease observed on MRI, decreased temperature sensation to cold in the distal lower extremities, decreased sensation to vibration in the distal lower extremities, decreased reflexes, mild dysmetria, and bilateral pes cavus

Note: This CNV was inherited from the proband’s mother who was noted to be similarly affected

P5 16p11.2 223 kb tandem duplication on SH2B1

Connective tissue disorder and hypermobile joints, speech delay, speech apraxia, autism, dysmorphic facial features, recent weight loss, short stature, and an abnormal response to traumatic pain

Note: Finding likely explains diagnosis of autism and related clinical findings, but there is no evidence to suggest that this patient’s connective tissue disorder is related to this CNV

P6 2q37.2→2qter, 3q29→3qter Mosaic unbalanced translocation Dysmorphic facial features and congenital anomalies, with scaphocephaly, prominent metopic ridge, hypoplastic supraorbital ridge, high arched eyebrows, epicanthus inversus, short upslanting palpebral fissures, ptosis, blepharophimosis, narrow upper lip, mild micrognathia or retrognathia, midline cleft palate, patent ductus arteriosus, palmar crease abnormalities, tapered fingers, and hypoplastic nails; notable other phenotypic features include failure to thrive, developmental delay, intellectual disability, profuse sweating during feedings, and tachycardia
P7 2pter→2p25.3, 16q23.3→16qter Unbalanced translocation Microcephaly and severe intellectual disability, with no speech and behavioral problems including repetitive, aggressive, and self-abusive behavior; patient described as having sleep difficulties, ataxic walking, and dysmorphic facial features including downslanting palpebral fissures, full lips, frontal upsweep, ptosis, strabismus, and dental crowding
P8 19q13.11-12 1.7 MB de novo deletion Progressive dystonia, prematurity (born at 28 weeks), dysarthria/anarthria, tongue dyskinesia, microcephaly, abnormal ocular movements, intellectual disability, some repetitive obsessive behaviors, and pyramidal tract signs on MRI; nonverbal and does not walk or eat independently; described as thin-appearing
P9 18p Tetrasomy 18p Severe global developmental delay, nonverbal, ataxia, feeding difficulties, strabismus, aggressive behavior, dysmorphic features including occipital plagiocephaly, downslanting short palpebral fissures, low-set posteriorly rotated malformed small ears, smooth philtrum, mild prognathism, bilateral camptodactyly in the 3rd, 4th, and 5th fingers with absent distal interphalangeal creases, hypoplastic thenar eminences, and a right single transverse palmar crease; facial paralysis as an infant and asymmetric crying face
P10 8p23.1 5.1 Mb gain (unknown de novo or inherited) Intermittent rash; telangiectasia; acroparesthesia; numbness, pain, and swelling of extremities; joint pain; facial flushing; and headaches; CT scan revealed hypoperfusion in the left parietal lobe relating to ischemia; he also has hypertrophic cardiomyopathy, bradycardia, expressive speech delay, and a learning disability
P11 6q22.1-31, 6q23.1, 11p15.4-3 Multiple large deletions on 6q, inserted duplication of 11p into chr17 Growth deficiency, microcephaly, intellectual disability with no speech, hyperactivity, large bulbous nose, epicanthal folds, short philtrum, small mandible, seizures; family history is pertinent for two maternal uncles who have little or no speech
P12 14q32.2 23 kb de novo mosaic deletion to the promoter of MEG3 Developmental delay, speech delay, behavioral difficulties, neonatal respiratory and feeding difficulties, hyperextensible and buckling phalanges, bilateral hallux valgus, and dysmorphic features including full cheeks, myopathic facies, prognathism, thick pinnas, strabismus, short forehead, bifrontal narrowing, midface hypoplasia, and anteverted nares
P13 15q11.2 604 kb maternally inherited deletion of BP1–BP2 in the Burnside–Butler susceptibility locus Episodes of ataxia, cyanosis, memory disturbance, speech difficulty, emesis, and severe pain in arms and legs, easy fatigue, constipation alternating with diarrhea, possibly due to intestinal dysmotility, as well as general abdominal distension and possible intussusception; ventricular tachycardia, frequent respiratory infections and rashes, and possible small fiber neuropathy were also noted; differential diagnoses include dysautonomias, mitochondrial disorders, energy depletion syndromes, and mast cell abnormalities
P14 16p13.11 1.6 Mb gain, unknown inheritance

Congenital inflammatory myopathy, hypotonia, muscle pain, absent reflexes, and motor delay; a muscle biopsy showed necrosis and paleness of sarcoplasma with eosinophilia, multiple vacuoles, and inflammatory infiltrate

Note: This CNV was reported as a pathogenic incidental finding for 16p13.11 microduplication syndrome

P15 7p22.1 749 kb deletion in PSM2 Phenotype not applicable as CNV was discovered upon Secondary Findings analysis
P16 chr21 Trisomy 21

Clinical diagnosis of Down syndrome (confirmed by karyotype). Additionally, patient is reported to have phenotypic features that are not consistent with a diagnosis of trisomy 21, including hypotonia that is more marked than expected, dermal ridge patterns with more arches than are typical, a small phallus, infantile spasms that are controlled on medication, a skeletal and long myopathic face,

lumbar lordosis, scapular winging, tapered calves, absent reflexes, ptosis, and a lurching pelvis when walking. The patient is unable to walk without a walker. Family history is notable for nemaline myopathy. The patient’s mother’s phenotype includes weakness in childhood and a muscle biopsy revealing nemaline rods, consistent with a diagnosis of nemaline myopathy. She could not run or jump as a child, although her clinical presentation improved over time. Currently, she is reported to have few residual features although she cannot run.

Note: CNV analysis revealed trisomy 21; in addition, a maternally inherited variant classified as likely pathogenic in ACTA1 was identified in both the proband and mother

P17c chr14 Mosaic trisomy 14 Developmental delay, ocular colobomas, low-set posteriorly rotated ears, hypomelanosis of Ito, solitary kidney, atrial and ventricular septal defects
P18c chr15 UPD15, paternal Global developmental delay with language delay, strabismus, coxa vulga, genu valgum, pes planus, low-set cupped ears with attached lobe, broad palate with alveolar ridge, short neck, inverted nipples, truncal obesity, broad-based ataxic gait, hypotonia, and lumbar lordosis
P19b,c chr16 UPD 16, paternal

Hypotonia, developmental delay, diffuse pachygyria with leukoencephalomalacia

Note: Paternally inherited UPD 16 was considered an incidental finding for this patient as there is no evidence linking paternal UPD 16 in association with disease

Note that these variants are not used in the aggregate statistics reported here.

CNV copy-number variant, MRI magnetic resonance image, UPD uniparental disomy.

aPatient phenotypic data were provided to Illumina Clinical Services Laboratory by the ordering physician via the completed test requisition form and accompanying medical notes.

bSample sequenced in prevalidation test development cohort. Note that these samples are not used in any reported aggregate statistics.

cVariant is outside of the clinical test definition but was observed in a development pipeline or as an incidental finding.