Student Seminar

1. Student Seminar • Tutor: Professor V. CN Wong • Group B(1) • Chiang Chi Lin, Chilene • Lai Yi Lam • Lee Yin Yin, Candice • Mui Wing Ho

2. Case • Chan Yu Kai • M/ 7 ½ years old • First consultation - 1yr 8mths • Presentation – Poor feeding since birth

3. History of Presenting Illness • Artificial formula • After birth: stayed in nursery for 20 days due to poor feeding: • Feeding 1 ½ oz X3 X 8 • 30 min to finish • No choking or cyanosis • 2 mths: “Does not want to eat” • Obstruction by tongue • Some vomiting after feeding • Consulted QE Paediatrics • Feed by syringe • ? GE reflux • 8 mths: Head trauma with right epidural haemorrhage • Required tube feeding • 1yr 8mths: referred to feeding team of DK

4. 1 yr 8 mths • Obs Hx – G1P1, 37wks, LSCS, 2kg • Antenatal –IUGR since 4 mths. 46 XY • Immunization – up to date • Family History • No parental consangunity. No MR, psychiatric illness, hearing problem, motor problem, speech problem • Father: 49, air conditioner techinician • Mother: 33, housewife • Only child • Past medical History • Feeding problem since birth • 8 mth – head trauma with right epidural haemorrhage. • Fall from low chair while sitting without support • Operated in QEH. • Required enteral feed for 1 year after operation. • Left sided clumsiness • Physiotherapy and occupational therapy

5. 1 yr 8 mths (20 mths) • Developmental History • Gross motor • Sit without support 9-10 mths (6mths) • Stand without support 14 mths (10mths) • Walk without support 17 mths (15mths) • Fine motor • Right hand dominance > 8 mths • Language • First word 12 mths (9mths) • At 20mths – about 10 single words (uses 2 or more words to make simple phrases) • Social • Feeding – requires tube feeding • Drank from cup with aid with water only. Refused milk or solid food. (18mths – holds spoon and gets food safely to mouth) • Gross hearing and vision – normal

6. 1 yr 8 mths (20 mths) • Griffiths Mental Developmental Scale • General IQ = 82 • Mental Age = 17 ¼ mth

7. 1 yr 8 mths • Neurological Examination • Toddler’s gait • Clumsy left side • Upper limb – increased pronater tone on left side • Lower limb – phasic spasticity of left hip adductor • ? Cranial nerves • Vision – normal • Hearing – normal • Diagnosis • Left mild hemiparesis • Global delay • Feeding difficulty • Failure to thrive • ? GE reflux • Etiology • Post epidural haemorrhage • Poor oromotor function

9. Causes of poor feeding • Healthy children • Parental factors • Environmental factors • Psychological factors • In children with GI tract disorders • Oral dysphagia • structural anomalies of the mouth and pharynx • central nervous system defects or injury • Pharyngeal dysphagia • enlarged tonsils, adenoids, and retropharyngeal abscess • Esophageal dysphagia • stricture, stenosis, atresia, stridor, and esophagitis • Gastro-oesophageal reflux

10. Special needs children • Chronic ill health • seizures, frequent upper respiratory infection (decrease motivation to eat, increased energy expenditure) • Cerebral palsy • Syndromes • E.g. Down's, Riley-Day, Angelman's, Silver-Russell, Pierre Robin syndromes; • Physical and structural abnormalities pertinent to feeding • poor lip closure • muscle rigidity or weakness • malocclusion • high palate • poor tongue movement • Aspiration • Reflux • difficulty with oromotor control • postural tone abnormalities • abnormal oromotor pattern and oral tactile sensitivity

11. 2-7 yrs old • FU at DK for • Feeding difficulty • Global developmental delay • Oromotor dyspraxia • Reduced vertical and horizontal (esp to the left) movement of tongue • No fasciculations or atrophy • No other neurological signs

12. Growth parameters • Weight • 2-6 yrs old: < 3rd percentile • 6-7 yrs old: 25 percentile • Height • 2-5 yrs old: ~ 3rd percentile • 5-6 yrs old: 10th percentile • 6-7 yrs old: ~ 25th percentile • Head circumference • 2-4yrs old: 3-10th percentile • 4-6 yr old: 10-25th percentile

13. Attended local kindergarten • 2-3 yrs old: Feeding problem at school. Requires teacher’s assistance. • 5-7 yrs old: Poor attention at class. Need to sit in the first row. Average performance. Mother chose to retake K3. Will enter local primary school this year. • Previous IQ scores according to the mother: 70 ( 5 yrs old), 80 (7 yrs old) • Lives with mother and father. Previous caretaker was grandmother until 8 mths old (after head trauma). Chief caretaker now is his mother. • Mother describes child has few friends. Poor attention at school but good attention when doing things that interests him e.g. reading picture books and watching cartoons.

14. 7 ½ yrs old • General Examination • Face: Triangular shaped face. Thin lipped. No other dysmorphic features e.g. single looped ears, hyperteleorism • Limbs: No obvious limb asymmetry. Incurved 5th finger of the right hand. • Skin: no neurocutaneous features e.g. café au lait patches. • Growth parameters • Weight: 20kg (25th percentile) • Height: 118cm (~ 45th percentile) • Head circumference: 51.5 cm (~ 40th percentile) • Chest – normal • Abdomen – normal. No undescended testes

15. Neurological • Observation: very active. Running around. Could ascend and descend stairs unaided. • Intelligence: normal. Able to tell examiner his name, age, full address and full name of school attended. • Social: blunt sentences. Does not listen to instructions of examiner • Speech: difficulty in pronouncing the “k” sound • Vision: Hypermetropia (5D) Astigmatism (2D) • Cranial nerves: limited vertical movement of the tongue. No fasciculations. No tongue atrophy. • Limbs: normal

20. Summary Chan Yu Kai M/ 7 ½ yrs old • Presented with poor feeding since birth • 2 mth: ? GE Reflux. • 8 mth: head trauma with right epidural haemorrhage • 1 yr 8 mth: assessment results show global developmental delay • 2-7 yrs: weight and height > & ~ 3 percentile, later pick up and now ~ 25 percentile • 7 yrs • normal IQ but ?hyperactive ? Attention deficit • Positive P/E findings: triangular shaped face, thin lips, clinodactyly

21. Ddx • GI disorder • GE reflux • Special needs children • Developmental delay  poor oromotor control • E.g. Cerebral palsy, Silver Russell syndrome, Pierre Robin sequence • Dysphagia after head trauma ( e.g. cranial nerve palsy) • Normal child • Psychiatric disorder e.g. ADHD, Aspergers’

28. Silver-Russell syndrome • Heterogeneous group of conditions of varying severity • 1953, 2 cases described by Silver • Low birth weight • Asymmetry • Growth retardation • 1954, 5 Similar cases by Russell

29. Clinical Features • SGA • Low birth weight • Reduced postnatal growth • Classical facial features • Asymmetry • Fifth finger clinodactyly • Café-au-lait spots

30. Classical facial features, by Russell • High forehead tapering • Small jaw • Prominent nasal bridge • Well-demarcated philtrum • Mouth angles down-turning

31. Other problems • Skeletal system • Delayed bone age in early childhood • Syndactyly of 2nd and 3rd toes • Neurological: Oromotor dyspraxia • Feeding difficulty, articulation problem • Urogenital system • Renal anomaly • Hypospadias • USUALLY normal intelligence • Excessive sweating (esp head and upper trunk)

32. Natural history • Early childhood slim and underweight for height • Gross motor developmental delay • Growth improvement in childhood or adolescent, still short stature • Less obvious facial features with age • IQ correlated with OFC(~30 % with learning disability)

33. Etiology • Mostly sporadic • Uniparental disomy of chromosome 7 • Isosomy of chromosome 7 • Others reported: • AR • X-linked • deletions of distal 15q • Ring chromosome 15 • Trisomy 18 mosacism • Others….

34. New Diagnostic criteria • Presence of 3 of the following • Low birth weight • Short stature • Classical facial features • Asymmetry • Clinodactyly

35. What can be done about? • Specialized schooling • Sx for urogenital abnomalies • GH supplement

36. Mental retardation • AAMR Definition • Substantial limitations in present functioning. • Significantly subaverage intellectual functioning, with related limitations in two or more of the following applicable adaptive skill areas: • Communication, Self-care, Home living, Social skills, Community use, Self-direction, Health and safety, Functional academics, Leisure, and Work. • Mental retardation manifests before age 18. (Luckasson et al., 1992, [25] p.5)"

37. Mental retardation • MR is subdivided into: • mild (IQ between 50 and 70), • moderate (IQ between 35 and 50), • severe (IQ between 20 and 35), • profound (IQ below 20). • Adaptive functioning sometimes relatively good, may mask the extent of the general intellectual functioning.

38. 3 steps of diagnosing MR • Step1 • diagnosis, determines eligibility • based on three cirteria: • IQ, adaptive skill level, and age of onset. • IQ determination is made on the basis of performance below 97% of same-age peers with comparable cultural backgrounds if appropriate standardized measure unavailable (Luckasson, 1992) [25].

39. 3 steps of diagnosing MR • Adaptive skill level determined with • standardized instruments such as the revised Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984) [38] • the Comprehensive Test of Adaptive Behavior (Adams, 1984) [1] in addition to narrative descriptions by the diagnostic team. • Age of onset before 18 reflects U.S. cultural norms about when an individual is expected to assume adult roles; this age may be different for different cultures (Schalock et al., 1994) [36].

40. 3 steps of diagnosing MR • Step 2: • Description, identifies a person's strengths and weaknesses. • Strengths and weaknesses of intellectual and adaptive skills must be described • Source identified by the multidisciplinary team for 10 skill areas: • communication, self-care, home living, social skills, community use, self-direction, health and safety, functional academics, leisure, and work (Luckasson et al., 1992) [25].

41. 3 steps of diagnosing MR • Step 3: • profile and intensities of needed supports, • describes the support function, activity, and level of intensity for each functional area requiring support identified in Step 2. • For example, if an individual had been identified in Step 2 as having a physical-health diagnosis, such as cerebral palsy, extensive supports identified in Step 3 may include a wheelchair and physical therapy.

42. Evaluation of the child with global developmental delay (GDD) • Obtain a detailed history and examination • Able to identify the etiology in 20-30% of GDD • Accurate prenatal/birth history and family history, together with a three-generation pedigree • Presence of dysmorphic features, minor anomalies, skin changes • A thorough neurological assessment • Complemented by photographs and videotaping (especially valuable in documenting posture, gait, any movement disorders, and behaviour characteristics)

43. Evaluation of the child with global developmental delay (GDD) • Refer for auditory and ophthalmological screening • Children with GDD are at risk to have primary sensory impairments of vision and hearing • Speech and language delay is often a feature of GDD and may be the result of a hearing loss

44. Evaluation of the child with global developmental delay (GDD) • Consider thyroid function test and metabolic screening if universal newborn screening not done • Thyroid function test (TSH +/- T4) • Metabolic screening (capillary blood gas, serum lactate and ammonia levels, serum amino acids and urine organic acids)

45. Evaluation of the child with global developmental delay (GDD) • Consider EEG if history of suspected seizures or epilepsy syndrome • Consider screening for autism or a language disorder • If there is a close family member with GDD • Specific tests for a known metabolic, genetic or structural nervous system disorder • Cytogentic screen and subtelomeric rearrangements

46. If no family history of GDD but with features suggestive of a specific diagnosis, direct testing may be utilized • Dysmorphic features in Down’s syndrome (karyotype), Fragile X (FMR1), Rett syndrome (MECP2), Praeder-Willi/Angelman (FISH), or hypothyroidism • History of intrapartum asphyxia or physical signs such as microcephaly, cerebral palsy, focal neurological signs or focal seizures may suggest acquired CNS injury or an underlying cerebral malformations (neuroimaging study preferably MRI) • Risk factors for lead poisoning/findings suggestive of lead intoxication (lead screening) • Loss/regression of developmental milestones, history of parental consanguinity, prior unexplained loss of a child or multiple miscarriages (metabolic screening, neuroimaging, EEG, cytogenetic studies, genetic and ophthalmologic consultations)

47. Evaluation of the child with global developmental delay (GDD) • If there is no feature suggestive of any specific diagnosis • Less likely to be associated with a definable disease and thus a stepwise approach is more appropriate • Includes initial neuroimaging (MRI), cytogenetic and fragile X screening • If negative, proceed to metabolic evaluation, testing for subtelomeric rearrangements, and genetic consultation, and test for Rett syndrome (Shevell et al, 2003)

48. Cytogenetics/molecular cytogenetics in the evaluation of MR • Genetic defects account for 28% of MR (Stevenson et al, 2003) • Cytogenetic studies at a 400-550 band resolution is the standard investigation for suspected chromosomal rearrangements and can detect microscopically visible rearrangements (>3MB) • 4p- (Wolf-Hirschhorn) and 5p- (cri du chat) syndromes are examples of microscopically visible deletions that mostly include the subtelomeric region and cause MR associated with a specific phenotype

49. Cytogenetics/molecular cytogenetics in the evaluation of MR • Submicroscopic rearrangements (<2-3MB) however cannot be detected by cytogenetics analysis alone, and may account for a significant proportion of MR cases with unknown etiology • The end of chromosomes (telomeres) are involved in the majority of translocations • The regions adjacent to telomeres are gene rich so that rearrangements involving telemere-adjacent DNA (subtelomeric) are more likely to have phenotypic consequences

50. Cytogenetics/molecular cytogenetics in the evaluation of MR • Once recognizable syndromes have been excluded, submicroscopic subtelomeric rearrangements are the commonest cause of undiagnosed moderate to severe MR (Knight et al, 1999) • Molecular cytogenetics enable the use of chromosome-specific probes for the detection of submicroscopic subtelomeric rearrangements • Techniques include fluorescent in-situ hybridization (FISH) of subtelomeric probes, and microsatellite markers (which can also detect uniparental disomy)