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Table 1 Clinical and cytogenetic characteristics of patients

From: Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder

Patient Initial karyotype Sex Age at last evaluation ASD Cognitive level Language Birth and early development Body measures Dysmorphic features Other Brain MRI
1a 46,XY,der(4)t(4;acro p)(p16.3;acro p)dn M 4 y Autism (DISCO) VIQ 67, PIQ 78, FSIQ 69 (WPPSI-R, 34 mo) Functional language Born at 42 wk, W +4.3 SD (gestational diabetes), neonatal hypoglycemia. Normal motor milestones 4 y: W and H +2-3 SD No dysmorphic features, mild strabismus Inguinal hernia Not done
2a 46,XY,t(5;18)(q12;p11.2)dn M 5 y Autism (ADI-R) DQ 52 (PEP-R, 40 mo) 1st words 36 mo, no sentences Born at 38 wk, W –0.6 SD, H –1 SD, OFC mean. Walked at 17 mo 5 y: W –1 SD, H +1 SD, OFC –0.4 SD No dysmorphic features, slender habitus, long fingers and toes, numerous secondary palmar creases Frequent otitis, eczema Small bilateral insular hypersignal suggesting myelinization delay (at 4 y)
3b 46,XY,inv(11)(p14q23.2)dn M 4 y Autism (ADI-R, ADOS) DQ 13 mo (Brunet Lezine-R, 4 y) Non-verbal Intrauterine growth retardation, born at 37 wk, W –3.5 SD, H –3.5 SD, OFC –2.5 SD. Delayed motor development, unable to walk at 4 y 42 mo: W, H and OFC –3 SD Mild dysmorphic features, high forehead, horizontal eyebrows, upslanting palpebral fissures, bulbous nose, smooth philtrum, thin upper lip, posteriorly rotated ears, single palmar crease, bilateral clinodactyly 5th finger Aggressiveness, anxiety, stereotypies, head banging, bilateral cryptorchidism, axial hypotonia, hyperlaxity Supratentorial ventricular enlargement, increased subarachnoid spaces (at 18 mo)
4a 46,XY,inv(2)(q14.2q37.3)mat (reported previously [15]) M 14 y Autism (ADI-R) VIQ 46, PIQ 50, FSIQ 46 (WISC-III, 14 y) 1st words 30 mo, 1st sentences 60 mo Born at 39 wk, W mean, H –0.5 SD, OFC –1.1 SD. Sat at 9 mo, walked at 14 mo 12 y: W +0.5 SD, H –0.5 SD, OFC mean Mild dysmorphic features, frontal bossing, flattened nasal bridge, deep-set eyes, downslanting palpebral fissures, thin upper lip Hyperactivity, head banging, anxiety, asthma, insulin-dependent diabetes, growth hormone deficit Normal (at 3 y)
5a 46,XX,inv(2)(p12q14.1)dn (benign cytogenetic variant) F 13 y Autism (ADI-R) DQ 30 (PEP-R, 6 y) Non-verbal Born at 39 wk, W +0.5 SD, H mean, OFC +1.9 SD. Sat at normal age, walked at 22 mo 13 y: W +3.5 SD, H +2 SD, macrocephaly (+4.2 SD) Mild dysmorphic features, narrow palpebral fissures, short philtrum, large hands and feet, one café-au-lait spot Stereotypies, self-injurious behavior, sleep disturbance, one episode of febrile seizure at 31 mo, normal EEG Chiari type I malformation, mild white matter hyperintensities (at 9 y)
6a 46,XX,inv(9)(p11q13)dn (benign cytogenetic variant) F 7 y Autism (ADI-R) Intellectual disability Isolated words Born at term, W +0.5 SD, H +0.9 SD. Walked at 12 mo 7 y 2 mo: W +3.8 SD, H +4.1 SD, OFC +1.7 SD No dysmorphic features Precocious puberty at 7 y, bone age 8 y, normal hormone levels, pulmonar stenosis, moderate systolic murmur Normal (at 7 y)
7a 46,XY,inv(5)(q13q34)dn M 18 y Autism (ADI-R) VIQ 93, PIQ 80, FSIQ 86 (WISC-III, 18 y) No delay, functional language Born at 40 wk, mean W, H and OFC. Sat at 9 mo, walked at 20 mo 18 y: W –1.4 SD, H mean, OFC +1.6 SD No dysmorphic features, mild clubbing Refraction error Myelinization delay (at 18 y)
8b 46,XY,t(9;19)(p12;q13.4)dn M 7 y Autism (ADI-R, ADOS) VIQ 83, PIQ 80, FSIQ 79 (WPPSI, 5 y 5 mo) 1st words 24 mo, 1st sentences 36 mo, functional language Born at term, W +1 SD, OFC +0.3 SD. Sat at 7 mo, walked at 11 mo NA No dysmorphic features ADHD Normal
9b 46,XX,t(X;5)(p11.2;q35.2)dn (reported previously [59]) F 8 y ASDc PIQ 58 (WISC-R at 8 y) Non-verbal, uses sign language Born at term, W +1 SD. Sat at 9 mo, walked at 21 mo 4 y: W and H mean, OFC +1 SD Mild dysmorphic features, prominent forehead, saddle nose, midface hypoplasia, high arched palate, generalized alopecia with scattered thin hair, umbilical hernia, pectus excavatum Hypomelanosis of Ito, pigmented lesions on the legs, achromic lesion on the back, hypotonia, hyperlaxity, flat feet, hypermetropia, febrile seizures, absence seizures, abnormal EEG. Skewed X inactivation of the normal chromosome (92%) Normal (at 6 y)
10a 46,XY,t(20;21)(q11.2;q21)dn M 12 y Autism (ADI-R) DQ 20 (PEP-R, 12 y) Non-verbal Born at 41 wk, W –1.7 SD, H –0.5 SD, OFC –1.1 SD. Sat at 9 mo, walked at 18 mo 12 y: W –1.8 SD, H mean, microcephaly (–3.6 SD) Dysmorphic features, low forehead, thick eyebrows, long nose, short philtrum, right single transverse palmar crease Strabismus, epilepsy (onset at 9 mo) Not done
11a 46,XY,t(9;16)(q3.2;p1.2)mat M 18 y Autism (ADI-R) VIQ 46, PIQ 46, FSIQ 40 (WISC-III, 14 y) Language delay, 1st phrases 5 y, functional language Born at term, W +1.3 SD, H +1 SD, OFC +2.1 SD. Sat at 8 mo, walked at 14 mo 18 y: W +3 SD, H mean, OFC +2.3 SD No dysmorphic features, short neck, brachymetatarsia of 4th and 5th rays Hyperactivity in childhood, strabismus, hypermetropia Not done
12a 46,XY,t(3;8)(q13.2;p23)mat M 5 y Autism (DSM-IV, CARS) VIQ 79, PIQ 74, FSIQ 77 (Stanford-Binet IV, 3 y 9 mo) 1st words 26 mo, 1st sentences 36 mo, few sentences at 5 y, dysarthric speech Normal pregnancy, delivery and early development; walked at 13 mo 4 y: W, H and OFC within normal limits No dysmorphic facial features, long ring finger, brachymesophalangia V, sandal gap Severe ADHD, pica, self-injurious behavior, partial complex epilepsy (onset at 4 y, currently seizure free on medication), chronic ear infections, chronic diarrhea, food allergies Not done
13b 46,XY,t(2;20)(q13;q13.33)mat M 22 y ASDc Intellectual disability Language delay, uses only a few words, answers with signs Born at term, W –0.8 SD, H –1 SD, OFC –1.1 SD. Sat at 11 mo, walked at 2 y 22 y: W +1.4 SD, H mean, OFC –1 SD No dysmorphic facial features, bilateral clinodactyly 5th finger, several café au lait spots Hyperactivity, aggressiveness, inappropriate laughter, hand stereotypies, unilateral strabismus, seizures at 7 mo, no recurrence after stopping treatment Normal (at 1 y)
14a 46,XX,inv(5)(p13.3q13.3)pat (benign cytogenetic variant) F 8 y Autism (ADI-R) DQ 55 (PEP-R, 5 y) 1st words 18 mo, 1st sentences before 3 y; echolalic language Dizygotic twin pregnancy, born at 27 wk, W 880 g. Walked at 18 mo 8 y: W mean, H and OFC +1 SD No dysmorphic features, long face, flat feet, tuberous angioma scar on scapula Insensitivity to pain Non specific white matter hypersignal (at 5 y)
15a 46,X,inv(Y)(p11q11)pat (benign cytogenetic variant) M 14 y Autism (ADI-R) DQ 15 (PEP-R, 14 y) Non-verbal Born at 38 wk, W –2.1 SD, H –1.5 SD, OFC –2 SD. Sat at 9 mo, walked at 13 mo 14 y: W +2 SD, H +1 SD, OFC mean Synophris, abnormal dental implantation (delayed tooth loss)   Normal (at 14 y)
16b 46,XY,t(2;13)(p23;q14)pat M 7 y Autism (ADI-R, ADOS) PIQ <1st %ile (Raven, 7 y 5 mo) 1st words 36 mo, 1st sentences 48 mo, functional language Born at term, W –1.2 SD, H +0.5 SD, OFC +0.7 SD. Sat at 20 mo, walked at 36 mo NA No dysmorphic features ADHD Normal
17a 46,XY,t(4;9)(p13;p23) (not maternal, father not tested) M 30 y Autism (ADI-R, ADOS) DQ <20 (PEP-R, 16 y) Non-verbal Born at term, W +0.7 SD, H +1 SD. Feeding difficulties, hypotonia, growth delay (–3 SD). Walked at 4 y 30 y: W –1 SD, H +1.1 SD, OFC –0.5 SD No dysmorphic features except for enophtalmia, low-set eyebrows, large ears, narrow hands Hyperactivity, severe sleep disturbance, insensitivity to pain, gastric and esophageal ulcers, abnormal EEG at 1 y (temporal lobe focus), no epilepsy Not done (encephalography at 6 mo: global ventricular dilatation)
18b 46,XY,t(2;13)(q22;q31) (not maternal, father not tested) M 4 y Autism (ADI-R, ADOS) IQ <1st %ile (Raven, 4 y 8 mo) Non-verbal Born post-term at 47 wk, W –0.8 SD, H –0.8 SD, OFC –0.6 SD. Sat at 20 mo, walked at 36 mo 4 y: W and H –0.5 SD, OFC –2 SD No dysmorphic features, brachyplagiocephaly ADHD, aggressiveness, anxiety Normal
  1. aPatients from the PARIS cohort; bpatients referred by the network of French cytogeneticists; cASD was not formally evaluated in these two patients. ADHD, attention deficit-hyperactivity disorder; ADI-R, Autism Diagnostic Interview-Revised; ADOS, Autism Diagnostic Observation Schedule; ASD, autism spectrum disorder; CARS, Childhood Autism Rating Scale; DISCO, Diagnostic Interview for Social and Communication Disorders; dn, de novo; DQ, developmental quotient; FSIQ, full scale IQ; H, height; IQ, intellectual quotient; mat, maternal; mo, months; MRI, magnetic resonance imaging; NA, not available; OFC, occipitofrontal circumference; pat, paternal; PEP-R, Psychoeducational Profile Revised; PIQ, performance IQ; SD, standard deviation; VIQ, verbal IQ; W, weight; WISC-III, Wechsler Intelligence Scale for Children, third edition; WISC-R, Wechsler Intelligence Scale for Children-Revised; wk, weeks; WPPSI-R, Wechsler Preschool and Primary Scale of Intelligence Revised; y, years.