approach to developmental delay in children

developmental delay

1. APPROACH TO A CHILD WITH DEVELOPMENTAL DELAY

2. Approach to Development Delay HISTORY INVESTIGATIONS EXAMINATION

3. History Family History Consanguinity Family history of GDD/ID Parent’s IQ Antenatal history Maternal drug intake( Phenytoin,opioids , isotretinoin) Maternal infection (CMV, HSV, Toxoplasmosis, rubella, syphilis) Maternal anemia Maternal folic acid intake Twin delivery Chromosomal abnormalities (Fragile X, Downs, Angelman, Turner) Birth history Prematurity Birth Asphyxia Birth Injury IUGR Neonatal HIE/ Seizures Neonatal jaundice Inborn errors of metabolism Congenital abnormalities ICU admissions Infections Congenital hypothyroidism

4. Anthropometry Weight Underweight - SAM Obesity - Prader- willi syndrome Height Short stature - Malnutrition, Turner, Noonan syndrome Large stature - Sotos syndrome Head circumference Microcephaly -Cerebral palsy, Angelman syndrome, fetal alcohol effects, Rett syndrome, Malnutrition Macrocephaly - Alexander syndrome, Hydrocephalus, Canavan syndrome, Sotos syndrome, MPS

5. Physical Examination Area Anomaly associated Head Flat occiput: Down syndrome, Zellweger syndrome Prominent occiput: trisomy 18 Delayed closure of sutures: hypothyroidism, hydrocephalus Craniosynostosis: Crouzon syndrome, Pfeiffer syndrome Delayed fontanel closure: hypothyroidism, Down syndrome, hydrocephalus, skeletal dysplasias Face Midface hypoplasia: fetal alcohol syndrome, Down syndrome Triangular facies: Turner syndrome, Russell-Silver syndrome Coarse facies: Mucopolysaccharidoses, Sotos syndrome Prominent nose and chin: fragile X syndrome Flat facies: Apert syndrome , Stickler syndrome Round facies: Prader-Willi syndrome Ref:Nelson Textbook of pediatrics , 21st ed

6. Eyes Hypertelorism: fetal hydantoin syndrome, Waardenburg syndrome Hypotelorism: holoprosencephaly sequence, maternal phenylketonuria effect Inner canthal folds/Brushfield spots: Down syndrome Slanted palpebral fissures: trisomies Prominent eyes: Apert syndrome, Beckwith-Wiedemann syndrome Lisch nodules: neurofibromatosis Blue sclera: osteogenesis imperfecta, Turner syndrome , hereditary connective tissue disorders Ears Large pinnae/simple helices: fragile X syndrome Malformed pinnae/atretic canal: Treacher Collins syndrome, CHARGE syndrome Low-set ears: Treacher Collins syndrome, trisomies, multiple disorders Ref:Nelson Textbook of pediatrics , 21st ed

7. Ref:Nelson Textbook of pediatrics, 21st ed Nose Anteverted nares/synophrys: Cornelia de Lange syndrome Broad nasal bridge: fetal drug effects, fragile X syndrome Depressed nasal bridge: Down syndrome, Achondroplasia Mouth Long philtrum/thin vermilion border: fetal alcohol effects Cleft lip and palate: isolated or part of a syndrome Micrognathia: Pierre Robin sequence , trisomies, Stickler syndrome Macroglossia: Hypothyroidism, Beckwith-Wiedemann syndrome Teeth Anodontia: ectodermal dysplasia Notched incisors: congenital syphilis Late dental eruption: Hunter syndrome, hypothyroidism Talon cusps: Rubinstein-Taybi syndrome Wide-spaced teeth: Angelman syndrome

8. Ref:Nelson Textbook of pediatrics, 21st ed Hair Hair Hirsutism: Hurler syndrome Low hairline: Klippel-Feil sequence, Turner syndrome Sparse hair: Menkes disease, argininosuccinic acidemia Abnormal hair whorls/posterior whorl: chromosomal aneuploidy (e.g., Down syndrome) Abnormal eyebrow patterning: Cornelia de Lange syndrome Neck Webbed neck/low posterior hairline: Turner syndrome, Noonan syndrome Chest Shield-shaped chest: Turner syndrome Genitalia Macroorchidism: Fragile X syndrome Hypogonadism: Prader-Willi syndrome

9. Extremities Short limbs: achondroplasia , rhizomelic chondrodysplasia Small hands: Prader-Willi syndrome Clinodactyly: trisomies, including Down syndrome Polydactyly: trisomy 13 , ciliopathies Broad thumb: Rubinstein-Taybi syndrome Syndactyly: de Lange syndrome Transverse palmar crease: Down syndrome Joint laxity: Down syndrome, fragile X syndrome, Ehlers-Danlos syndrome Skin Hypopigmented macules/adenoma sebaceum: tuberous sclerosis Café au lait spots and neurofibromas: neurofibromatosis Facial port-wine hemangioma: Sturge-Weber syndrome Nail hypoplasia or dysplasia: fetal alcohol syndrome, trisomies Ref:Nelson Textbook of pediatrics , 21st ed

10. BASELINE INVESTIGATION: Biochemistry: Blood: Calcium ,Phosphate , creatinine kinase , Thyroid function test , lactate, VLFAs Acylcarnitines , transferrin isoforms. Urine: Organic acids , amino acids , glycosaminoglycans and oligosachharides , sialic acid, sulphite , succinylpurine , creatine and guanidinoacetate Genetic: Chromosomal microarray , Molecular diagnostic test for fragile X Radiological: MRI brain ( microcephaly , pigmentary skin anomalies, abnormal neurological examination) Ref:Nelson Textbook of pediatrics , 21st ed

11. Additional biochemical investigations in specific cases : Urine: Purines and pyrimidines Blood: Ammonia ,copper and ceruloplasmin, cholesterol and 7-dehydrocholesterol, biotinidase , white cell lysosomal enzymes , plasmalogens, pipecolic acid and phytanic acid, cholesterol Cerebrospinal fluid (CSF) : Glucose (including CSF to plasma glucose ratio), glycine( including CSF glycine to plasma glycine ratio), lactate , pyruvate, neurotransmitters Hair: Amino acid analysis TMS & GC-MS Ref:Nelson Textbook of pediatrics , 21st ed

12. GENETIC INVESTIGATIONS IN SPECIFIC CASES : 1. Specific genetic test( sanger sequencing and copy number analysis ) for suspected monogenic disorder 2. Next generation sequencing (and copy number analysis) of panel of genes eg suspected x linked disorder or based on phenotype , eg epilepsy or neuro- imaging abnormality 3. Chromosomal microarray and /or standard karyotype in cultured skin fibroblasts Methylation tests at imprinted chromosomal loci, including methylation – specific MLPA test for prader Willi and angelman syndromes 4. Whole genome sequencing/Whole Exon Sequencing Ref:Nelson Textbook of pediatrics , 21st ed

13. Red flags suggestive of inborn errors of metabolism: Family history of IEM or GDD or unexplained neonatal death Consanguinity Intrauterine growth retardation Failure to thrive G rowth abnormality Recurrent episodes of vomiting ,ataxia , seizures ,lethargy , coma Regression in developmental milestones Behavioural or psychiatric problems Movement disorder Facial dysmorphism Organomegaly , Severe hypotonia Sensory defects, especially progressive for e g cataract, retinopathy Non congenital progressive spine deformities Neuroimaging abnormalities Ref:Nelson Textbook of pediatrics , 21st ed