ciaccio_23_DD_discovery_cases-case5

  Ciaccio C et al. 2023

 3 yrs. 8 mos.

 F

 Developmental delay

 Developmental milestones: delayed ability to walk (2 years). Motor and musculoskeletal evaluation: mild oculomotor dyspraxia, mild gait ataxia, axial hypotonia with hypertonia of the lower limbs in infancy. Behavioral/psychiatric evaluation: impulsivity, aggressive behavior, emotional dysregulation, low frustration tolerance, constant seeking of attention, repetitive conducts. EEG: slow background activity, poorly organized sleep pattern. Brain imaging: abnormal brain MRI (blurred and wavy folia boundaries, facing cerebellar hemispheres, flattened course of folia white matter stem). Additional medical history: esotropia. Dysmorphic features: deep-set eyes, epicanthus, tented upper lip.

 

 125968430

 133620905

  7652476

 GRCh38

 Deletion

 No

  ciaccio_23_DD_discovery_cases-case6

  Ciaccio C et al. 2023

 6 yrs. 10 mos.

 M

 Developmental delay

 Developmental milestones: mildly delayed ability to walk (1 year 4 months). Language and communication evaluation: dysarthria. Motor and musculoskeletal evaluation: oculomotor dyspraxia, orobuccal dyspraxia, slight terminal tremor, dysmetria, mild gait ataxia, valgus feet, flat feet, 5th toe clinodactyly, infantile hypotonia, joint hypermobility. Behavioral/psychiatric evaluation: attention deficit, low frustration tolerance, food selectivity, mild signs of anxiety. EEG: spikes on vertex and centroparietal regions during drowsiness and sleep. Brian imaging: abnormal brain MRI (vermis hypoplasia, facing cerebellar hemispheres, flattened course of folia white matter stem). Additional medical history: esotropia, gastroesophageal reflux. Dysmorphic features: triangular face, thin and mildly upslanting palpebral fissures, narrow nasal ridge, thin lips, tented upper lip, large ears. Growth parameters: short stature (height <3rd %ile, -2.8 SD), decreased body weight (<3rd %ile, -2.6 SD), microcephaly (HC 3rd %ile, -2.2 SD).

 IQ 93 (WISC)

 127141197

 133769456

  6628260

 GRCh38

 Deletion

 No

  engchuan_15_ASD_discovery_cases-case4386_1

  Engchuan W , et al. 2015

 N/A

 N/A

 ASD

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

 

 127849708

 129780525

  1930818

 GRCh38

 Duplication

 No

  girirajan_13a_ASD_discovery_cases-14091.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

 126452054

 133565398

  7113345

 GRCh38

 Deletion

 Yes

  han_22_ASD/DD/ID_discovery_cases-case15D3272

  NA NA

 2 yrs. 4 mos.

 M

 Developmental delay and intellectual disability

 Speech delay

 Intellectual disability

 127989125

 133613639

  5624515

 GRCh38

 Deletion

 No

  iourov_12_ASD/ID/EP_discovery_cases-case20

  Iourov IY , et al. 2013

 2 yrs. 4 mos.

 M

 Developmental delay

 Syndactyly, facial dysmorphisms

 Mild developmental delay and cognitive delay

 126504191

 132256595

  5752405

 GRCh38

 Deletion

 No

  jiao_19_EP/DD/ID_discovery_cases-caseDD18006638

  Jiao Q , et al. 2019

 1 yr.

 Female

 Developmental delay

 Developmental milestones: global developmental delay. Motor and musculoskeletal evaluation: abnormal posturing. Additional medical history: esotropia.

 

 127602806

 130292806

  2690001

 GRCh38

 Deletion

 No

  kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001975

  Kaminsky EB , et al. 2011

 NA

 NA

 Developmental delay/intellectual disability/ASD

 Clinical profile NA

 Cognitive profile NA

 127852284

 129780378

  1928095

 GRCh38

 Duplication

 Yes

  kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00003770

  Kaminsky EB , et al. 2011

 NA

 NA

 Developmental delay/intellectual disability/ASD

 Clinical profile NA

 Cognitive profile NA

 127500483

 133620674

  6120192

 GRCh38

 Deletion

 Yes

  kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004372

  Kaminsky EB , et al. 2011

 NA

 NA

 Developmental delay/intellectual disability/ASD

 Clinical profile NA

 Cognitive profile NA

 126256585

 133613938

  7357354

 GRCh38

 Deletion

 Yes

  kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005379

  Kaminsky EB , et al. 2011

 NA

 NA

 Developmental delay/intellectual disability/ASD

 Clinical profile NA

 Cognitive profile NA

 127640489

 132776585

  5136097

 GRCh38

 Deletion

 Yes

  maini_18_ASD/DD/ID_discovery_cases-case_unknown8

  NA NA

 N/A

 N/A

 NDD/MCA/dysmorphic features

 CNV was identified in an individual with one or more neurodevelopmental disorders (NDD), multiple congenital anomalies (MCA), and/or dysmorphic features (detailed clinical information was not available). CNV classified as pathogenic

 

 127338746

 133590615

  6251870

 GRCh38

 Deletion

 No

  maini_18_ASD/DD/ID_discovery_cases-case_unknown9

  NA NA

 N/A

 N/A

 NDD/MCA/dysmorphic features

 CNV was identified in an individual with one or more neurodevelopmental disorders (NDD), multiple congenital anomalies (MCA), and/or dysmorphic features (detailed clinical information was not available). CNV classified as pathogenic

 

 127338746

 133590615

  6251870

 GRCh38

 Duplication

 No

  mazzonetto_24_ASD/DD/ID_discovery_cases-caseDECIPHER530533

  NA NA

 

 F

 Intellectual disability

 

 Intellectual disability (HP:0001249).

 126970685

 133797422

  6826738

 GRCh38

 Deletion

 No

  minhas_13_ASD_discovery_cases-case1

  Minhas HM , et al. 2013

 7 yrs.

 M

 ASD

 Diagnosis of ASD based on evaluation with ADOS-Module 3 and ADI-R. Birth/neonatal history: born healthy after normal pregnancy (birth weight of 7 lb.); noted to have feeding difficulties and difficulty fixing and tracking visually (eventually diagnosed with alternating esotropia for which he had corrective surgery with partial vision improvement). Developmental milestones: motor skills showed considerable delay secondary to generalized hypotonia; unable to sit without support until 18 months, unable to walk indepdently until 3 years; noted to have fine motor delays; delayed language development; characteristics of verbal apraxia noted at 14 months; at 23 months case had age-appropriate receptive language skills, but expressive language skills fell 2 SDs below mean; first clear words at 3 years of age, after which language development advanced rapidly. Language and communication evaluation: assessment using Differential Ability Scales-II (DAS-II) suggested that expressive vocabulary stronger than receptive language skills); PPVT-4 evaluation showed single-word receptive language within average range (score of 101, 53rd %ile); ADOS showed usage of complex language primarily involving short sentences with occasional use of unusual language and some repetitive questioning. Behavioral/psychiatric evaluation: limited eye contact, spontaneous gesturing and range of facial expression; engaged in some atypical social interactions; limited ability to describe emotions; exhibited some sensory-seeking behaviors; noted to be very sensitive to certain textures; developed fixations and obsessional behavior; intermittent motor tics, including blinking. Epilepsy/seizures: no history of seizures. Dysmorphic features: none reported. Growth parameters: head circumference in 24th %ile at 28 months of age (no other parameters reported). Family history: younger brother with possible diagnoses of PDD-NOS and Tourette syndrome (minhas_13_ASD_discovery_cases-case2); born to healthy non-consanguienous parents with no family history of ASD or intellectual disability (parents had previous pregnancy that ended in miscarriage); father found by FISH analysis to be carrier of balanced translocation involving chromosomes 10 & 11.

 Assessment with Differential Ability Scales-II (DAS-II) indicated overall cognitive abilities in low-average range (GCA score of 89, 23rd %ile); assessment of adaptive behavior using Vineland-II showed adaptive behavior composite in moderately low range (communication, receptive communication, and expressive communication in adequate range; daily living skills and socialization in moderately low range; motor skills in low range).

 126442244

 133472578

  7030335

 GRCh38

 Deletion

 Yes

  minhas_13_ASD_discovery_cases-case2

  Minhas HM , et al. 2013

 5 yrs.

 M

 PDD-NOS and Tourette syndrome

 Primary diagnosis of PDD-NOS and Tourette syndrome among diagnoses considered by case's child psychiatrist (case not available for standardized testing). Medical history: case exhibited strabismus and GERD at age 3-4 months along with intermittent episodes of tonic stiffening; also noted to have decreased fine motor skills, apraxia, difficulty with motor planning, and mild axial and appendicular hypotonia; some concern regarding torticollis (given tentative diagnosis of Sandifer syndrome); MRI at age of 3 years 7 months revelaed left cerebellar juvenile pilocytic astrocytoma, which was removed shortly thereafter and led to significant improvement (case now able to run downhill, demonstrated improved fine motor skill, and reduced episodes of intermittent eye fluttering and unresponsiveness). Behavioral/psychiatric evaluation: subsequent to surgery to remove left cerebellar juvenile pilocytic astrocytoma, patient exhibited OCD symptoms and tics similar to brother; these symptoms continued up to time of report. Dysmorphic features: none reported. Growth parameters: head circumference at 25th %ile at age of 12 months (no other parameters given). Additional genetic information: carried unbalanced translocation involving chromosomes 10 & 11. Family history: older brother with ASD diagnosis (minhas_13_ASD_discovery_cases-case1); born to healthy non-consanguienous parents with no family history of ASD or intellectual disability (parents had previous pregnancy that ended in miscarriage); father found by FISH analysis to be carrier of balanced translocation involving chromosomes 10 & 11.

 

 126442244

 133472578

  7030335

 GRCh38

 Deletion

 Yes

  miyake_23_ASD_discovery_cases-case26864

  Miyake N et al. 2023

 NA

 F

 ASD

 Case clinically diagnosed with ASD based on DSM-V criteria.

 

 128040889

 133568459

  5527571

 GRCh38

 Deletion

 Yes

  nguyen_13_DD/ID/MCA/ASD_discovery_cases-249233

  Nguyen LS , et al. 2013

 N/A

 F

 Developmental delay/intellectual disability

 Database: DECIPHER. Indication for study: Depressed/flat nasal bridge, ear lobule, hypohidrotic or dry skin, large ears, intellectual disability/developmental delay, microcephaly, patchy skin defects, prominent heels, scoliosis

 Developmental delay/intellectual disability

 128780229

 133661283

  4881055

 GRCh38

 Duplication

 N/A

  nguyen_13_DD/ID/MCA/ASD_discovery_cases-256335

  Nguyen LS , et al. 2013

 N/A

 F

 DD/ID/MCA

 Database: DECIPHER. Indication for study: NF (nothing found/no phenotypic information available)

 

 126778471

 133590967

  6812497

 GRCh38

 Deletion

 N/A

  nguyen_13_DD/ID/MCA/ASD_discovery_cases-256897

  Nguyen LS , et al. 2013

 N/A

 M

 DD/ID/MCA

 Database: DECIPHER. Indication for study: NF (nothing found/no phenotypic information available)

 

 128114950

 133620645

  5505696

 GRCh38

 Deletion

 N/A

  pfundt_16_NDD_discovery_cases-case107

  Pfundt R , et al. 2016

 N/A

 N/A

 NDD

 Disease cohort: neurodevelopmental disorder. Description: 10qter deletion de novo

 

 125816176

 133220113

  7403938

 GRCh38

 Deletion

 Yes

  plaisancie_14_ADHD/ID_discovery_cases-case1

  Plaisanci J , et al. 2013

 9 yrs.

 F

 ADHD and ID

 Birth/neonatal history: born prematurely at 36 weeks of amenorrhea after uneventful pregnancy (mother was 26 and father 29 at time of birth); birth weight of 2630 g (50th %ile), length of 47 cm (50th %ile), and OFC of 36 cm (97th %ile); neonatal period complicated by hypotonia and feeding difficulties requiring enteral nutrition for one month. Developmental milestones: sat alone at age of 12 months, walked at age of 23 months; first words at 17 months of age, first sentences at age of 3 years; found to have good fine motor skills at age of 3.5 years; understood simple and blended verbal orders but had more difficulty in understanding complex verbal orders; able to perform symbolic activities. Motor and musculoskeletal evaluation: limb abnormalities (brachydactyly, clinodactyly of 2nd and 5th fingers, planovalgus foot deformity with short metatarsals of 4th and 5th toes. Behavioral/psychiatric evaluation: initially quite sociable; sleeping disorder noticed in first year of life in form of repeated awakenings during the night; hyperactivity, impulsivity, aggressivity, self-injurious behavior, verbal stereotypies, bruxism, trichotillomania, and decreased social interactions from age of 5 years (led to treatment with antipsychotic medication); developed anxiety, perseverations, and disinhibitions at age of 8 years in parallel to persistent sleep disturbance with early awakening (antipsychotic medication stopped due to poor response and anxiolytic recently initiated). Brain imaging: cerebral MRI showed moderate cerebellar hypoplasia with ventricular asymmetry. Dysmorphic features: tall forehead, thick eyebrows, deep set eyes, broad nasal tip, long philtrum, thin upper lip, bifid uvula, broad chin, macrotia, widely spaced nipples. Other anomalies: significant history of ENT infections; astigmatism. Growth parameters: weight of 16.5 kg (+1 SD), height of 99.5 cm (+0.5 SD) and OFC of 50.5 cm (+1 SD) at age of 3.5 years. Family history: first child of healthy related parents (both of Caucasian origin) with no personal or family history of intellectual disability, behavioral difficulties, or malformations; mother had no history of miscarriages; healthy brother.

 Mild intellectual disability; general cognitive ability within below-average range of intellectual functioning, as measured by verbal IQ (score of 82) and performance IQ (score of 79), using WPPSI at age of 5.5 years; WISC-IV at ge of 9 years revealed mild ID (Full-scale IQ of 53), decreased score primarily due to significant regression of non-verbal abilites from borderline to mild, while verbal abilities were relatively preserved (dissociation between verbal and non-verbal IQ evocative of manual dyspraixa with visuo-spatial defect).

 128628266

 133586004

  4957739

 GRCh38

 Deletion

 Yes

  plaisancie_14_ADHD/ID_discovery_cases-case2

  Plaisanci J , et al. 2013

 6 yrs.

 F

 ADHD and ID

 Birth/neonatal history: born at 37 weeks gestation after pregnancy marked by intra-uterine growth retardation and single umbilical artery with excessive amniotic fluid, in the context of gestational diabetes; presented with post-natal growth retardation in first year of life requiring enteral nutrition for three years. Developmental milestones: sat alone at age of 12 months, walked at 26 months, said first words at age of 30 months. Behavioral/psychiatric evaluation: concentration deficit, limited attention span. Brain imaging: normal. Other anomalies: significant history of ENT infections; severe astigmatism; posterior cleft palate. Dysmorphic features: microcephaly, tall forehead, hypertelorism, broad nasal ridge, long philtrum, thin vermillion of the lips, broad chin, macrotia. Growth parameters: growth retardation; weight of 12 kg (-2 SD), height of 98 cm (-0.5 SD) and OFC of 45 cm (-3.5 SD). Family history: second child of unrelated patients, both of Caucasian origin; maternal half-sister (case4) and mother (case3) both present with similar neurobehavioral phenotypes; maternal grandfather described as person with behavioral problems and difficulties in social interactions.

 Moderate intellectual disability

 126442053

 133402080

  6960028

 GRCh38

 Deletion

 Yes

  plaisancie_14_ADHD/ID_discovery_cases-case3

  Plaisanci J , et al. 2013

 N/A

 F

 ADHD and ID

 Motor and musculoskeletal evaluation: limb abnormalities (5th finger clinodactyly). Behavioral/psychiatric evaluation: bradypsychia, apathy. Other features: wore eyeglasses for astigmatism and myopia; one miscarriage in obstetric history. Dysmorphic features: tall forehead, hypertelorism, broad nasal ridge, long philtrum, thin vermillion of the lips, broad chin, macrotia. Growth parameters: growth retardation; height of 145 cm. Family history: two female offspring (case2 and case4) with similar neurobehavioral phenotypes; father described as person with behavioral problems and difficulties in social interactions.

 Moderate intellectual disability; attended specialized school when she was young.

 126442053

 133402080

  6960028

 GRCh38

 Deletion

 No

  plaisancie_14_ADHD/ID_discovery_cases-case4

  Plaisanci J , et al. 2013

 16 yrs.

 F

 ADHD and ID

 Birth/neonatal history: born at term after uneventful pregnancy; birth weight of 2700 g and length of 46 cm; uneventful neonatal period. Developmental milestones: presented with global developmental delay; sat at 19 months of age, said her first words late. Motor and musculoskeletal evaluation: limb abnormalties (5th finger clinodactyly, short metatarsals of 5th toes). Behavioral/psychiatric evaluation: spasmophilia, concentration deficit, limited attention span; treated by pediatric psychiatrist for anxiety attacks from an early age. Other features: significant history of ENT infections; wears eyeglasses for astigmatism and myopia. Dysmorphic features: tall forehead, hypertelorism, broad nasal ridge, long philtrum, thin vermillion of the lips, broad chin, macrotia. Growth parameters: growth retardation; weight of 55 kg (+0.5 SD), height of 146.5 cm (-2.5 SD) and OFC of 54.5 cm (-0.5 SD) at age of 16 years. Family history: maternal half-sister (case2) and mother (case3) both present with similar neurobehavioral phenotypes; maternal grandfather described as person with behavioral problems and difficulties in social interactions.

 Moderate intellectual disability; currently in special school for moderate learning difficulties.

 126442053

 133402080

  6960028

 GRCh38

 Deletion

 No

  sanchis_juan_23_ASD/DD/ID_discovery_cases-caseG003425

  Sanchis-Juan A et al. 2023

 NA

 M

 Movement disorder

 Patient presented with movement disorder.

 

 128143881

 131050454

  2906574

 GRCh38

 Deletion

 No

  shin_15_ASD/DD/ID_discovery_cases-case9

  Shin S , et al. 2015

 1 yr.

 M

 Developmental delay

 Developmental delay, lipomeningomyelocele

 

 128360440

 133612882

  5252443

 GRCh38

 Deletion

 No

  utine_14_DD/ID/ASD_discovery_cases-case8

  Utine GE , et al. 2014

 5 yrs.

 M

 Developmental delay and autism/autistic features

 Referred at age of 1.5 years for developmental delay. Birth/neonatal history: delivered at 38 weeks of gestation with birth weight of 2750 g. Developmental milestones: head control at 2 months of age, sitting without support at 10 months of age, walking with support at 18 months of age; walked at 3.5 years of age. Language and communication evaluation: no words at age of 5 years. Behavioral/psychiatric evaluation: autism/autistic features. Epilepsy/seizures: no (doubtful seizure at age of 40 days). Brain imaging: normal. Dysmorphic features: long face with bitemporal narrowing, large ears, strabismus, thin upper lip, mildly elevated palate. Growth parameters: weight of 9.7 kg (3rd-10th %ile), height of 84 cm (75th %ile), and head circumference of 45 cm (<3rd %ile) at initial referral; remained microcephalic at follow-up visit. Family history: first child of healthy consanguineous parents; mother revealed to have balanced reciprocal translocation 46,XX,t(10;20)(q26.2;q13.2).

 MIld DD/ID (mean area of delay/disability: global)

 N/A

 N/A

  1400000

 Unknown

 Deletion

 Yes