Table 3. Overview of all patients giving karyotype, phenotype and De Vries score.
|
Patient |
Karyotypea |
Array platformb |
No. of CNVsc |
Phenotyped |
Adjusted De Vries scoree |
|---|---|---|---|---|---|
| Two-breakpoint aberrations | |||||
| 1 | t(X;3)(p21.3;p25.1) | 32k | 3 | Dolichocephaly, long face, strabism, full tip of the nose, prominent columella, dysmorphic ears, short philtrum, hyperthyroidism, severe DD, speech delay, convulsions, hypotonia | 4 |
| 2 | t(X;10)(p22.32;q22.2) | 244k | 4 | Short stature, microcornea, iris coloboma, cataract, short and broad hand and feet, hirsutism, adipositas, secundary amenorrhoea, severe DD, blindness, hypotonia | 4 |
| 332, pt A | t(X;19)(p11.4;q13.3) | 32k | 6 | Autism, borderline DD (IQ 82), mild hypotonia | 0 |
| 4 | inv(X)(q22.1q28) | 32k | 7 | Down-slant palpebral fissures, open mouth appearance, pes planus, convulsions, speech delay, autism | 2 |
| 5 | t(1;2)(p35;q33) | 105k | 4 | Chondrodysplasia punctata, severe short stature, low-set dysplastic ears, flat nose, hemangioma, PMR, deafness, hypertonia | 5 |
| 6 | t(1;6)(p22.1;q15) | 244k | 7 | Macrocephaly, cerebral atrophy, deep-set eyes, prominent fore head, midface hypoplasia, low nasal bridge, short philtrum, low-set ears, pectus excavatum, small hands with broad short phalanges of the thumbs, pes planus, severe DD | 6 |
| 7 | t(1;8)(p22.1;p23.3) | 244k | 6 | Severe DD, absent tendon reflexes, autism, hypotonia | 2 |
| 8 | t(1;14)(q42.1;q31.1) | 32k | 7 | Dysplastic ears, mild DD, obstipation | 2 |
| 9 | t(1;16)(q21;p11.2) | 250k | 6 | Pre-auricular tag, DD (IQ 50), behavioral and sleep problems | 2 |
| 10 | t(1;17)(p36.1;q11) | 244k | 5 | Mild DD, obstipation, recurrent airway infections | 1 |
| 11 | inv(1)(p22.3p34.1) | 32k | 4 | Macrocephaly (+4.5 SD), dolichocephaly, mild ventriculomegaly, hypertelorism, upward slanted and narrow palpebral fissures, micrognathia, proximally placed thumbs, mild DD | 5 |
| 12 | t(2;9)(q34;p22) | 244k | 2 | Broad tip of the nose, micrognathia, single palmar crease, convulsions, deceased at age 2 months | NA |
| 13 | t(2;10)(p13;p14) | 105k | 3 | Broad tip of the nose, moderate/severe DD, convulsions, hypotonia | 2 |
| 1433 | t(2;10)(p23;q22.1) | 32k | 6 | Birth weight >P98, macrocephaly, sparse hair, hypoplastic alae nasi, dysplastic ears, moderate DD, psychotic disorder, hypotonia, nasal speech, disturbed serine metabolism | 4 |
| 15 | t(2;10)(p25;q26) | 250k | 5 | Epicanthus, club foot, hyperlaxity, mild DD (IQ 64), affective psychotic episodes | 2 |
| 16 | t(2;10)(q22;q22.3) | 244k | 10 | Growth retardation, down-slanting palpebral fissures, small nose, mild/moderate DD, convulsions, hypotonia, obstipation | 4 |
| 17 | t(2;10)(q23;p12) | 244k | 8 | Narrow fore head, high narrow palate, mild retrognathia, mild DD, autism | 3 |
| 1828 | t(2;14)(q37.3;q13) | 105k | 2 | IUGR, microcephaly, iris coloboma, laryngomalacia, umbilical hernia, inguinal hernia, severe PMR | 6 |
| 19 | t(2;15)(p22.2;p11) | 32k | 3 | Left-sided hemiparesis, upturned nose, 3 maxillary incisors, absent lower canine tooth, dilatation of aorta, scoliosis, arachnodactyly, mild DD, pubertas tarda, hyperlaxity | 5 |
| 20 | t(2;17)(p25;q23) | 250k | 3 | No dysmorphisms, eczema, PMR, speech delay, IQ 50–60 | 1 |
| 21 | t(2;18)(q23;q23) | 250k | 6 | Macrosomia at birth, bulbous nose, high narrow palate, pointed chin, tibial bowing, obesity, mild DD | 4 |
| 22 | inv(2)(q11.2q33) | 32k | 5 | High birth weight (>P98), deep-set eyes, short palpebral fissures, high bridge of the nose, micrognathia, high palate, micropenis, large hands, mild DD, aggressive behavior | 4 |
| 23 | t(3;12)(p13;p13.3) | 244k | 4 | Macrocephaly, macro-orchidism, nervus opticus atrophy, kyphosis, DD | 4 |
| 24 | t(4;8)(p16.1;p23.1) | 244k | 3 | Short stature, pre-auricular tags, synophris, prognathia, epicanthus, broad nasal bridge, thin upper lip, wide spaced teeth, mild DD, behavioral problems | 4 |
| 25 | t(4;12)(p12;q13.2∼13.3) | 244k | 3 | Hypertelorism, large ears, broad tip of the nose, short philtrum, thin upper lip, recurrent infections, no DD | 2 |
| 26 | t(4;16)(q33;q12.2) | 244k | 8 | Microcephaly, moderate/severe DD, hypotonia | 3 |
| 27 | t(4;17)(q23;q21) | 244k | 4 | Short stature (<P3), cerebral atrophy, strabism, scoliosis, severe DD, pes plani, autism, hypotonia | 4 |
| 28 | t(5;7)(p15.1;p22) | 32k | 5 | Upturned nose, mild DD, speech delay, autism, obsessive eating disorder | 2 |
| 29 | t(5;10)(q33;q25) | 250k | 4 | High birth weight (P98), blepharophimosis, epicanthus, strabism, long face, prominent nose, aplasia of nails, hip dysplasia, obesity, sensorineural deafness, severe DD, hypotonia | 5 |
| 30 | t(5;17)(p15.3;q25.3) | 32k | 6 | Macrocephaly, dolichocephaly, mild hypertelorism, epicanthus, short philtrum, micrognathia, overriding 2nd and 4th toes, mild conductive hearing loss, severe DD, speech delay, mild hypotonia | 6 |
| 31 | inv(5)(q14q33) | 32k | 2 | Protruding tongue, down-slanting palpebral fissures, strabism, posteriorly rotated ears, hirsutism, moderate DD, speech delay, autistic spectrum disorder | 3 |
| 32 | t(6;9)(q21;p24) | 250k | 3 | Severe DD, no speech, convulsions, mild hypotonia | 2 |
| 33 | t(6;11)(p12.3;p14.2) | 32k | 10 | Macrocephaly, strabism, high palate, hypertrichosis lumbosacralis, cryptorchidism, camptylodactyly dig V, pes plani valgi and metatarsus adductus, moderate DD, speech delay, mild sensorineural deafness, mild hypotonia | 5 |
| 34 | t(6;11)(q16.2;p15.1) | 250k | 5 | Epicanthus, severe DD, no speech, mild hypotonia | 3 |
| 35 | inv(6)(p11.1q21) | 32k | 6 | Eye disorder, mild to moderate DD | 2 |
| 36 | t(7;15)(p14;p11.2) | 244k | 7 | Microcephaly, small nose, dysplastic ears, low-set left ear, clinodactyly, cryptorchidism, severe DD, West syndrome | 5 |
| 37 31, pt 3 | inv(7)(p22q21.3) | 244k | 5 | Ectrodactyly of both hands and feet, atriovenous malformation of right hand, autism, no DD | 1 |
| 38 | t(8;14)(q21.2;q12) | 32k | 5 | Microcephaly, partial agenesis corpus callosum, deep-set eyes, strabism, high palate, open mouth appearance, scoliosis, pectus excavatum, short distal phalanges, severe DD, absent speech, convulsions, obstipation | 7 |
| 39 | t(10;16)(q24.1;p11.2) | 244k | 8 | Epicanthus, hypogonadism, obesity, mild DD, autism | 2 |
| 40 | t(12;14)(q13.1;q32.3) | 244k | 6 | Trigonocephaly (familial), mild dysplastic ears, no DD | 2 |
| 41 | t(12;14)(q24.1;q11.2) | 244k | 5 | Long narrow face, sparse hair, broad nasal bridge, umbilical hernia, scoliosis and asymmetrical thorax, mild DD, hypotonia with hypertonia of extremities | 3 |
| 4222, pt 8 | t(12;15)(q24.1;q21.1) | 244k | 9 | Marfan phenotype, broad nasal bridge, short philtrum, long and small fingers and toes, celiac disease, PMR, hypotonia, no intellectual disability | 3 |
| 43 | t(13;17)(q32;q21) | 32k | 4 | Deceased 1 day after uneventful pregnancy and birth, enlarged liver, steatosis | NA |
| 44 | t(17;22)(q23;q12.2) | 32k | 4 | Long narrow face, down-slanting palpebral fissures, retrognathia, severe scoliosis, pectus excavatum, arachnodactyly, short 4th metatarsals, hallux valgus, mild/moderate DD, cutis marmorata | 5 |
| 4529 | t(18 ;20)(q21.1 ;q11.2) | 32k | 12 | Broad, square face, high narrow palate, bilateral single palmar crease, pes planus, mild DD | 3 |
| 46 | t(19;21)(q13.3;q22.3) | 244k | 5 | Microcephaly, epicanthus, high nasal bridge, overfolded helices, valvular pulmonary stenosis, pectus excavatum, mild webbing of the fingers, delayed speech development | 6 |
| Complex chromosome rearrangements | |||||
| 47 | ins(5;17)(pter;p13.33p13.1) | 32k | 9 | Short stature (<P3), microcephaly, broad nasal bridge, thin upper lip, ASD, mild DD, persistent diarrhea | 6 |
| 48 | ins(1;11)(p22;q23.1q24.3) inv(1)(p13q23) | 32k | 2 | Short stature, mild trigonocephaly, epicanthus, upslant palpebral fissures, short nose, hearing loss, carp mouth, short 4th metatarsal bone left, pes planus, moderate DD, convulsions, obesity | 5 |
| 49 | der(2)ins(8;2)(q2?;p15p21), der(8)ins(8;2)inv(p?;q?) | 32k | 4 | Short stature (<P3), microcephaly, epicanthus, dysplastic ears, carp mouth, severe gastro-oesophageal reflux, kyphoscoliosis, contractures, rocker bottom feet, severe DD, absent speech, mild hypotonia | 8 |
| 50 | der(2),der(10),der(18) | 250k | 4 | Microcephaly, severe PMR, hypotonia | 3 |
| 51 | der(6)t(6;9)(p21.3;q22) ins(6;13)(p21.3;q?21q31), der(9)t(6;9),der(13)ins(6;13) | 32k | 5 | Birth weight <P3, short stature (<P3), microcephaly, enlarged 4th ventricle, ptosis, strabism, broad high nasal bridge, low dysplastic ears, cleft palate, micrognathia, ASD, clinodactyly dig V, severe speech delay, hypotonia, compulsive behaviour, obstipation | 9 |
| 52 | t(10;18;14)(p15.3;q12.2;q32.3) | 244k | 6 | Sotos syndrome (NSD1 mutation), height and head circumference >P99, broad high forehead, hypertelorism, broad nasal bridge, overfolded helices, pectus excavatum, mild DD, autism | NA |
| 5334 | der(2),der(3),der(7),der(11) | 32k | 7 | Hypertelorism, everted large nose, full lips, pectus carinatum, short fingers, convulsions, severe DD, absent speech | 5 |
| 54 | t(2;6;12;3)(q24;q23;q12;p13) | 250k | 5 | PMR, hypotonia | 1 |
a
Based on conventional karyotype and FISH analysis.
b
32k=32k BAC array; 105k=Agilent 105k oligonucleotide array; 244k=Agilent 244k oligonucleotide array; 250k=Affymetrix 250k SNP array.
c
The total number of copy number variations (CNVs) detected, including well-known benign CNVs. See Table 4 for potentially causative copy number alterations.
d
ASD=atrial septal defect; DD=developmental delay; PMR=psychomotor retardation.
e
See Table 2, NA=not applicable.