de_la_hoz_15_ID_discovery_cases-case1

  de la Hoz AB , et al. 2015

 11 yrs.

 F

 Intellectual disability and autistic features

 Birth/neonatal history: unremarkable pregnancy; born at term (39 weeks gestation) by normal delivery; birth weight of 2400 g (<3rd %ile), head circumference of 33.5 cm (<25th %ile); Apgar scores of 7 and 10 at 1 and 5 minutes; no remarkable observations in perinatal period. Developmental milestones: first evaluated at age of 6 months due to poor response to stimuli and lack of social smile, clinical examination at this time revealed significant motor developmental delay; able to walk despite motor clumsiness without support at 20 months; speech difficulties with marked expressive language disorder and global learning problems. Language and communication evaluation: speech difficulties at age of 11 years. Motor and musculoskeletal evaluation: significantly improved motor skills at age of 11 years. Behavioral/psychiatric evaluation: autistic features including stereotypic movements and difficulties with eye contact; social interaction difficulties at 11 years. Brain imaging: no abnormalities on brain MRI at age of 9 years. Dysmorphic features: long face, prominent chin, broad forehead, broad large mouth with widely spaced upper front teeth, slightly large and detached ears. Growth parameters: growing proportionately with age. Family history: first-born child of healthy non-consanguineous parents with no family history of congenital abnormalities or intellectual disability.

 Severe intellectual disability. Received cognitive stimulation therapy from the age of 12 months; psychometric assessment revealed an IQ of 40 at 7 years of age; learning disability at age of 11 years.

 60475583

 68466302

  7990720

 GRCh38

 Deletion

 Yes

  girirajan_13a_ASD_discovery_cases-13830.p1

  Girirajan S , et al. 2013

 N/A

 N/A

 ASD

 Diagnosis of ASD based on meeting criteria on the Autism Diagnostic Observation Schedule (ADOS) and on the Autism Diagnostic Interview, Revised (ADI-R)

 N/A

 60807942

 66269322

  5461381

 GRCh38

 Deletion

 Yes

  kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000795

  Kaminsky EB , et al. 2011

 NA

 NA

 Developmental delay/intellectual disability/ASD

 Clinical profile NA

 Cognitive profile NA

 61970847

 68465832

  6494986

 GRCh38

 Deletion

 Yes

  krumm_15_ASD_discovery_cases-case13830.p1

  Krumm N , et al. 2015

 N/A

 Male

 ASD

 Proband from the Simons Simplex Collection (SSC). Family type: Quad

 

 61562287

 66263379

  4701093

 GRCh38

 Deletion

 Yes

  larson_17_ASD_discovery_cases-case6

  NA NA

 N/A

 F

 ASD and psychosis

 Female, learning disabilities, psychosis onset mid teens, diagnosis of psychosis NOS, FDR history of depression. CNV not reported in DGV.

 Learning disabilities

 63346147

 64453601

  1107455

 GRCh38

 Deletion

 No

  okumura_14_DD/ID_discovery_cases-case1

  Okumura A , et al. 2014

 4 yrs. 1 mo.

 M

 Developmental delay/intellectual disability and autistic features

 Referred to outpatient neurology clinic at 7 months of age due to developmental delay. Birth/neonatal history: fetal growth retardation; born at 35 weeks gestation by emergency C-section due to premature rupture of membranes; birth weight of 2096 g (10th %ile), length of 43.0 cm (10th %ile), and head circumference of 34.0 cm (90th %ile); Apgar scores of 8 and 10 at 1 and 5 minutes; mild respiratory distress requiring oxygen supplementation at 7 days; otherwise unremarkable postnatal course. Developmental milestones: sitting at 12 months, walking without support at 43 months; expressive language at 49 months of age. Langauge and communication evaluation: speech delay (no expressive language until 49 months of age). Motor and musculoskeletal evaluation: mild hypotonia. Behavioral/psychiatric evaluation: autistic features (poor eye contact, no social smile, stereotyped behaviors (including staring at a simple object, head-banging, shuddering-like movement, rubbing head on the floor, and repeating simple movements such as hand flapping), and preference for solitary play beyond 4 years of age. Brain imaging: unremarkable cranial MRI at 12 months of age. Dysmorphic features: upswept frontal hair, low-set posterior rotated ears, arched downslanting eyebrow, prominent forehead, epicanthic folds, micrognathia, hypertelorism, broad nasal bridge, short philtrum, camptodactyly of the bilateral 5th fingers. Growth parameters: short stature; height of 91.5 cm (-2.3 SD) and weight of 11.5 kg (-2.1 SD) at age of 49 months. Family history: monozygotic twin with similar phenotype; born to healthy non-consanguineous parents with no family history of congenital anomalies or intellectual deficits.

 Severe developmental delay/intellectual disability; development quotient of 33 (as measured by Kyoto Scale of Psychological Development 2001 at the age of 23 months)

 60472496

 67385119

  6880000

 Unknown

 Deletion

 No

  okumura_14_DD/ID_discovery_cases-case2

  Okumura A , et al. 2014

 4 yrs. 1 mo.

 M

 Developmental delay/intellectual disability and autistic features

 Referred to outpatient neurology clinic at 7 months of age due to developmental delay. Birth/neonatal history: fetal growth retardation; born at 35 weeks gestation by emergency C-section due to premature rupture of membranes; birth weight of 1530 g (<3rd %ile), length of 39.0 cm (<3rd %ile), and head circumference of 28.7 cm (3rd %ile); Apgar score of 8 and 9 at 1 and 5 minutes; mild respiratory insufficiency requiring oxygen supplementation and IV aminophylline; feeding difficulty that gradually worsened with bilous vomiting; diangosed with intestinal malrotation and transferred to NICU of surgical treatment at 5 days of age (repaired using Ladd procedure, no surgical complications noted); discharged from hospital at age of 34 days. Developmental milestones: sitting at 14 months, walking without support at 49 months; expressive language at 49 months of age. Langauge and communication evaluation: speech delay (no expressive language until 49 months of age). Motor and musculoskeletal evaluation: mild hypotonia. Behavioral/psychiatric evaluation: autistic features (poor eye contact, no social smile, stereotyped behaviors (including staring at a simple object, head-banging, shuddering-like movement, rubbing head on the floor, and repeating simple movements such as hand flapping), and preference for solitary play beyond 4 years of age. Brain imaging: cranial ultrasound revealed dilation of lateral ventricles and flat anterior fontanelle; serial MRI scans revealed nonprogressive mild ventricular dilation throughout clinical course. Additional medical history: slowly progressive ventriculomegaly observed, endoscopic third ventriculostomy performed at 12 months of age. Dysmorphic features: upswept frontal hair, low-set posterior rotated ears, arched downslanting eyebrow, prominent forehead, epicanthic folds, micrognathia, hypertelorism, broad nasal bridge, short philtrum, camptodactyly of the bilateral 5th fingers. Growth parameters: short stature; height of 84.3 cm (-4.2 SD) and weight of 10.4 kg (-2.6 SD) at age of 49 months. Family history: monozygotic twin with similar phenotype; born to healthy non-consanguineous parents with no family history of congenital anomalies or intellectual deficits.

 Severe developmental delay/intellectual disability; development quotient of 34 (as measured by Kyoto Scale of Psychological Development 2001 at the age of 23 months)

 60472496

 67385119

  6880000

 Unknown

 Deletion

 No

  schwaibold_13_ID/DD/ASD_discovery_cases-case3

  Schwaibold EM , et al. 2013

 18 yrs.

 M

 Intellectual disability and autistic features

 Birth/neonatal history: pregnancy complicated by renal colic of mother at 16th gestational week and several violent assaults by father; spontaneous birth in 43rd gestational week (20 days after due date); birth weight 10th-25th %ile, birth length 10th-25th %ile, OFC 3rd %ile; very agitated and easily frightened as an infant. Developmental milestones: sitting at 15 months, walking at 3 years (gait on tiptoes). Language and communication evaluation: expressive language never developed; uttered sounds or made gestures to express himself; understanfding was better than active speech and could follow simple orders at age of 12 years; received speech therapy (in part due to severe hypersalivation and dismissive sensitivity to orofacial contact). Motor and musculoskeletal evaluation: gait on tiptoes; physiotherapy due to high muscle tone in lower limbs. Behavioral/psychiatric evaluation: demonstrated prolonged stages of screaming up to early adolescence; displayed autistic features, but started to develop eye contact and had friendly behavior in adolescence. EEG: abnormal beta activity assessed as unspecific sign at age of 7 years 9 months. Other features: severe hypersalivation, dismissive sensitivity to orofacial contact in adolescence; sleep disturbances which improved under medication and with further development; still needed diapers at night at age of 18 (seldom wet himself during day). Dysmorphic features: broad & mostly opened mouth with prominent chin and widely spaced teeth (partly with broken ends as case liked chewing hard things), long and slender face with deep-set eyes and flat occiput, fair skin and hair. Brain imaging: brain MRIs at ages of 4 years and 10 years revealed defect in temporal lobe (anamnestically). Family history: second child of non-consanguineous parents; healthy half-sister; history of father unknown (father not available for evaluation).

 Intellectual disability; attended therapeutic school from age of 7 years, received occupational and speech therapy

 59457445

 64176436

  4718992

 GRCh38

 Deletion

 Yes

  streata_22_ASD/DD/ID_discovery_cases-case214

  NA NA

 NA

 F

 Developmental delay and intellectual disability

 Global developmental delay, speech and/or language delay or impairment, congenital anomalies, facial dysmorphism.

 Severe intellectual disability

 62160193

 66319115

  4158923

 GRCh38

 Deletion

 No