chan_25_DD/ID_discovery_cases-case1

  NA NA

 10 yrs.

 F

 Developmental delay, intellectual disability, seizures, and autistic features

 Birth/neonatal history: born at 39 weeks gestation after an uneventful pregnancy by elective C-section due to maternal complications of a previous pelvic fracture; birth weight 2.5 kg (Z-score -1.73); mild neonatal jaundice requiring phototherapy; sleepy and difficulty feeding during the first two months of life. Develolpmental milestones: all developmental domains delayed from infancy with hypotonia and gross motor delay (sat unassisted at 10 months, crawled at 13 months, walked with hand holding at 3 years, walked independently with a preference for tiptoe at 4 years), fine motor delay (pincer grip at 2.5 years), delayed expressive and receptive language (babbled and imitiated sounds at 2.5 years, repeated single words and understood one-step instructions at 5 years, had a vocabulary of fewer than 50 words by 9 years), and delayed social communication. Language and communication evaluation: assessment by the Mullen Scales of Early Learning at 4 years 9 months showed receptive language skills equivalent to a 16-month-old and expressive language skills equivalent to 15 months. Motor and musculoskeletal evaluation: diagnosed with spastic diplegic cerebral palsy; increased tone in the lower limbs (normal elsewhere); walked independently with toe-walking; assessed as level II under the Gross Motor Function Classification System (GMFCS); bone age most closely corresponded to a 12-year-old female. Behavioral/psychiatric evaluation: challenging behaviors present from early life; reduced interest in others in infancy; at 16 months she was not responsive to parental voice, did not have separation or stranger anxiety, and started head hanging when upset; behaviors of biting, scratching, and pulling the hair of other children, particularly when tired, angry, frustrated or when she met a new child, at 5 years; increasingly more aggressive behavior as she grew older with occasional displays of defiance and anger by refusal to eat; more frequent and escalating challenging behaviours of self-injury through biting and hitting, and towards others by biting, scratching and pushing, at 9 years; assessment by ADOS-2 at 4 years 9 months showed an overall score suggestive of a clinical diagnosis (social communication difficulties, including the use of eye contact and vocalisations/speech to engage socially with others, and restricted and repetitive behaviours, including hand flapping, were present); assessment by ABC-C suggested challenging behaviors in a number of areas including aggressive, stereotypic, sluggish and hyperactive behaviors. Epilepsy/seizures: presumptive diagnosis of frontal lobe seizures following episodes of night-time waking involving eye opening, an appearance of looking fearful, shaking, stiffening of her body, followed by an attempt to bite her hands in mid-childhood. Brain imaging: brain MRI at approximately 2 years of age showed prominent perivascular spaces in the periventricular white matter and some residual terminal zones of myelination; MRI scan at 9 years showed reduced cerebral white matter volume, patchy FLAIR hyperintensities, tiny Rathkes cleft cyst, and areas of unusual sulcation, possibly due to reduction in white matter volume. Additional medical history: right exotropia; signs of puberty at 9 years of age (Tanner Stage 3 for breast and pubic hair development). Dysmorphic features: mild retrognathia, long face, broad nose, prominent ears. Growth parameters: height of 135 cm (Z score -0.67) and weight of 30.6 kg (Z-score -0.44) at 10 years, head circumference of 50 cm (Z-score -1.32) at 8 years 10 months. Family history: second child of healthy non-consanguineous parents of Indian ancestry.

 Moderate-severe intellectual disability (formal cognitive assessment not completed due to difficulties with engagement).

 19839089

 30073260

  10234172

 GRCh38

 Quintuplication

 Yes

  chen_16_ASD/DD/ID/EP_discovery_cases-case1

  Chen CP , et al. 2016

 21 yrs.

 M

 ASD, DD, ID, and epilepsy

 Birth/neonatal history: amniocentesis at 27 weeks of gestation identified a sSMC derived from chromosome 15; unremarkable prenatal ultrasound findings; birth weight of 3434 g; delivery at term with no phenotypic abnormalities. Developmental milestones: developmental delay. Lanaguge and communication evaluation: poor speech. Motor and musculoskeletal evaluation: hypotonia; ataxic gait. Behavioral/psychiatric evaluation: autism. Epilepsy/seizures: epilepsy. Growth parameters: height of 161 cm, weight of 56 kg. Family history: mother was 35 years old, gravida 3, para 2; father was 37 years old; parental karyotypes were normal; no family history of congenital malformations. Karyotype: 47,XY,+invdup(15)(pter->q13::q13->pter).

 Intellectual disability

 20480966

 30097840

  9616875

 GRCh38

 Triplication

 Yes

  wintle_10_ASD_discovery_cases-AN03935

  Wintle RF , et al. 2011

 19

 M

 Autism

 Autism

 

 19813473

 30201158

  10387686

 GRCh38

 Duplication

 Yes

  wintle_10_ASD_discovery_cases-AN14829

  Wintle RF , et al. 2011

 26

 F

 Autism

 Suspected autism

 

 19811075

 30210092

  10399018

 GRCh38

 Duplication

 Yes