Table 1.
CNV identified from exome sequencing
| Sample | Sex | CP subtype | GMFCS | Gestation (weeks + days) | Additional phenotypes | Maternal | Position (Cytoband) Inheritance | Type | Pathogenicity prediction and known phenotypes |
|---|---|---|---|---|---|---|---|---|---|
|
67067P Trio |
F | D | 3 | 27 + 4 | BW: 89th percentile. PVL, NICU stay, central sleep apnoea (moderate/severe), asthma, home oxygen, hypermetropic astigmatism, hypogammaglobulinaemia, lumbar scoliosis (mild), small infraorbital telangiectasia, good cognition | IVF pregnancy, history of stillbirth, preterm labour, difficult extraction, obstetrical bleeding (coagulopathy), foetal distress, emergency caesarean delivery |
1:145112323-149201987 (1q21.1) De novo |
Dup | Pathogenic. ASD, ID, ADHD, developmental coordination disorder, delayed speech, macrocephaly, cardiac problems, scoliosis, hypotonia, abnormal gait and/or agility.27 |
|
181463P Duo |
F | Q | 4 | 37 + 5 | BW: 7th percentile. IUGR, NICU stay. CNV events in this individual result from a de novo unbalanced translocation | Fetal distress, emergency caesarean without onset of labour, decreased fetal movements from 32 weeks, smoked during pregnancy. |
1:241728236-249240000 (1q43-q44) De novo |
Dup | Pathogenic. Macrocephaly, ID, prominent forehead, micrognathia/retrognathia.21 |
|
X:1-50350659 (Xp22.33-p11.22) De novo |
Del | Pathogenic. Turner Syndrome. Xp22 deletion previously reported in CP.10 | |||||||
|
150432P Duo |
F | D | 2 | 41 + 3 | BW: 19th percentile. ASD, toe walker, DD. CNV events in this individual result from a de novo unbalanced translocation | Hypotension, induced vaginal delivery, no complications |
2:1-2550499 (2p25.3) De novo |
Del | Pathogenic. ID, obesity, ASD, ADHD, delayed psychomotor development.19 Previously reported in CP.10 |
|
20:54945507-62960000 (20q13.2-q13.33) De novo |
Dup | Pathogenic. Role in CP uncertain. DD, cardiac malformation, clinodactyly of 5th finger, receding chin, protruding upper lip, large low set ears, upslanting palpebral fissures, epicanthus, microphthalmia, high scalp.37 | |||||||
|
157439P Trio |
M | D | 3 | 29 + 2 | BW: < 1 percentile. Epilepsy, DD, cleft lip and palate, ASD, twin to twin transfusion syndrome (donor), IUGR with NICU stay. Twin brother with the same variant has milder but similar symptoms (GMFCS 1) | Fibromyalgia syndrome, fetal distress, elective caesarean delivery without onset of labour |
3:33759248-34277749 (3p22.3) De novo |
Del | Likely pathogenic. This locus includes PDCD6IP. Support from knockout mouse model28 and zebrafish in this study. |
|
143425P Trio |
M | RH | 38 + 3 | BW: 13th percentile. Epilepsy, stroke in utero | History of miscarriage and stillbirths, giardia infection during pregnancy, spontaneous vaginal delivery, fetal distress |
16:29474649-30200303 (16p11.2-p12.2) De novo |
Del | Pathogenic. ASD, Speech anomalies, hypotonia with hyporeflexia, altered agility, seizures, macrocephaly, Chiari I malformation.26 | |
|
192475P Duo |
M | RH | 3 | 36 + 0 | BW: 77th percentile. DD, bilateral talipes, abnormal arch and branching of the heart, polymicrogyria, T-cell immunodeficiency, mandibular osteomyelitis, laryngomalacia, NICU stay | History of miscarriages, premature labour by spontaneous vaginal delivery |
22:18655870-21480623 (22q11.21) De novo (inferred) |
Del | Pathogenic. 22q11.2 deletion syndrome, congenital heart disease, immunodeficiency, palatal abnormalities, hypocalcaemia and ID.23 Previously reported in CP.9 |
|
183465P Trio |
F | D | 3 | 34 + 0 | BW: 66th percentile. Twin 1 with vanishing twin syndrome for twin 2 (gender not stated), NICU stay | Placental abruption due to clotting disorder causing bleeding in second half of pregnancy, emergency caesarean after onset of labour |
22:18656485-21463730 (22q11) De novo |
Dup | Pathogenic. 22q11.2 duplication syndrome. ID, behavioural disorder, delayed psychomotor development, hearing impairment, seizures and heart abnormalities.25 Previously reported in CP11 |
|
165447P Duo |
M | Dy | 38 + 4 | BW: 63rd percentile. Perinatal stroke, NICU stay | Hypertension, induced vaginal delivery, no complications |
2:54893010-55200400 (2p16.1) Unknown |
Dup | Uncertain. This locus harbours the brain-expressed EML6 gene. | |
|
187469P Duo |
F | Dy | 5 | 37 | BW: 16th percentile. Signs of ASD, not formally diagnosed, DD, anxiety. Previously identified de novo balanced translocation 46,X,t(X;1)(q13.1; q32.1) | Maternal diabetes, maternal hypertension, anemia, emergency caesarean |
2:106498314-107074142 (2q12.2) Maternal |
Dup | Uncertain. Similar duplications in DECIPHER have unrelated phenotypes. No known disease genes in this interval. |
|
105114P Trio |
F | LH | 38 | BW: 59th percentile. MRI at 9 m: Right MCA territory encephalomalacia, consistent with previous infarct, low protein C level | Gastric infection during pregnancy, spontaneous vaginal delivery, tight cord |
2:125668980-127806247 (2q14.3) Maternal |
Del | Uncertain. No similar deletions in DECIPHER. Down regulation of GYPC is associated with hereditary elliptocytosis. | |
|
129411P Trio |
F | Q | 5 | 27 | BW: 5th percentile, IUGR | Smoked during pregnancy, major bleeding, breech, emergency caesarean |
3:9831395-9908996 (3p25.3) Paternal |
Dup | Uncertain. No similar duplications in DECIPHER. No known disease genes in this interval. |
|
108117P Trio |
M | LH | 1 | 39 | BW: 66th percentile. Borderline ID, epilepsy, anxiety, left homonymous hemianopia, MRI 3d, 5 y and 7 y: Right MCA territory infarction and extensive encephalomalacia involving the central regions, frontal, parietal and occipital lobes, NICU stay | Fetal distress, spontaneous vaginal delivery |
5:76989059-77563443 (5q14.1) Maternal |
Dup | Uncertain. No similar duplications in DECIPHER. AP3B1 (Hermansky-Pudlak Syndrome OMIM: 608233). |
|
164446P Duo |
F | D | 2 | 27 + 0 | BW: 30th percentile. Hyperbilirubinemia, hypertonia, respiratory distress syndrome, NICU stay | Preterm infection, history of miscarriages and preterm births incompetent cervix, threatened miscarriage, preterm labour spontaneous vaginal delivery |
6:17282979-17987418 (6p22.3) Maternal |
Dup | Uncertain. This locus has potential for involvement in CP. Six individuals in DECIPHER with similar sized duplications (260928, 270332, 270990, 287970, 295582 and 331142). Global DD, behavioural disorder, microcephaly, short stature and ID. |
|
132414P Trio |
M | H | 1 | 40 + 1 | BW: 92nd percentile. Epilepsy, von Willebrand disease, NICU stay | Urinary condition and threatened miscarriage, depression, fetal distress emergency caesarean after onset of labour |
9:1056659-2923296 (9p24.3-p24.2) De novo |
Dup | Uncertain. This locus has potential for involvement in CP. Homozygous loss of function mutations in VLDLR cause cerebellar ataxia, intellectual disability and disequilibrium syndrome [OMIM: (CAMRQ1) 224050] |
|
101110P Single |
M | SH | 2 | 29 | BW: 98th percentile. Plagiocephaly, ASD, PVL, DD, neonatal seizures, obesity, right convergent squint, previous central apnoea, double hernia (39 w), twin 2 with female twin 1 deceased in utero, NICU stay | History of infertility, polycystic ovarian syndrome, gestational diabetes, hypertension, obstetrical bleeding for entire pregnancy, preterm labour, fetal distress, growth restricted emergency caesarean. |
9:131733020-132481734 (9q34.11) Unknown |
Dup | Uncertain. This locus has potential for involvement in CP. Two individuals in DECIPHER with similar sized overlapping duplications (256548 and 340614); both with ID. One individual (340614) had delayed fine and gross motor development. |
|
89098P Trio |
F | SD | 3 | 28 + 3 | BW: 7th percentile. PVL, IUGR, NICU stay | Chorioamnionitis, funisitis, GBS, preterm labour emergency caesarean delivery |
10:73822516-74987970 (10q22.1-q22.2) De novo |
Del | Uncertain. This locus has potential for involvement in CP. ASCC1 [OMIM: 614215] rare autosomal recessive congenital myopathy with similarity to spinal muscular atrophy.38 MICU1 [OMIM: 605084] recessive myopathy with motor and speech delay, progressive proximal muscle weakness and learning difficulties.39 |
|
49049P Trio |
M | RH | 1 | 35 | BW: 5th percentile. MRI at 3 y: Unilateral periventricular grey matter heterotopia, with two subependymal nodules on the lateral wall of the right lateral ventricle, IUGR, low protein C level, blood clotting issues, NICU stay | Spontaneous vaginal delivery |
14:35593381-35871320 (14q13.2) Paternal |
Dup | Uncertain. A SNP (rs1048990) that results in up regulation of PSMA6 may be associated with increased risk of myocardial infarction.40 |
|
180462P Duo |
F | D | 4 | 40 | BW: 27th percentile. Holoprosencephaly, diabetes insipidus, GERD, bilateral cleft lip and palate, epilepsy, global DD, hearing loss | Milroy’s disease, fever during pregnancy, threatened labour at 32 weeks, spontaneous vaginal delivery |
16:2906033-3071871 (16p13.3) Unknown |
Del | Uncertain. No similar duplications in DECIPHER. Does not overlap CREBBP |
|
104113P Trio |
M | Dy, Q | 4 | 40 + 2 | BW: 31st percentile. NE secondary to intrapartum anaphylaxis, neonatal seizures, hypotonia in all 4 limbs, DD, short stature, gastronomy fed, undescended testes, kyphosis, sialorrhea with drooling, nose bleeds, NICU stay | Threatened miscarriage emergency caesarean after onset of labour. |
19:2076893-2901121 (19p13.3) De novo |
Del | Uncertain. This locus has potential for involvement in CP. Two similar individuals in DECIPHER (269826 and 287279): Macrocephaly, DD, generalized hypotonia, abnormal dentition, bone abnormalities, ectodermal dysplasia, ID, pachygyria |
|
46046P Duo |
F | D,Dy | 2 | 39 | BW: 40th percentile. Ultra sound 2d: Global cerebral oedema. MRI at 8d: bilateral infarction of frontal and parietal lobes, dyspraxia, neonatal seizures, in special class | Maternal hypertension, gastric infection during pregnancy, emergency caesarean, fetal distress |
20:47711417-47989806 (20q13.13) Maternal |
Dup | Uncertain. Two individuals in DECIPHER with similar duplications: 265056 (delayed puberty, growth hormone deficiency, short stature) and 341719 (specific learning disability) |
|
120402P Trio |
M | D | 4 | 26 + 3 | BW: 16th percentile. Epilepsy, twin 2 (gender of twin 1 unknown), NICU stay | Preterm labour, spontaneous vaginal delivery |
X:99663478-100290718 (Xq22.1) X-linked |
Dup | Uncertain. This locus has potential for involvement in CP. Five individuals with X-linked or unknown inheritance in DECIPHER (258232, 278836, 291903, 326486, 337860). ID, ASD, aplasia or hypoplasia of the cerebellar vermis, microcephaly, strabismus, hypermetropia, hypotonia, seizures. |
F female, M male, S spastic, D diplegia, R/L/H right/left/hemiplegia, Q quadriplegia, Dy dyskinesia, ASD autism spectrum disorder, ADHD attention deficit hyperactivity disorder, BW birth weight, d/m/y days/months/ years, DD developmental delay, GBS group B Streptococcus infection, ID intellectual disability, IUGR intrauterine growth restriction, MCA middle cerebral artery, NE neonatal encephalopathy, NICU neonatal intensive care unit, PVL periventricular leukomalacia