This document provides information on approaching developmental delay. It defines global developmental delay as delays in two or more domains of development in children under 5 years old. The causes of developmental delay are categorized as prenatal (genetic and acquired factors), perinatal, and postnatal-environmental. The approach involves taking a detailed history, physical and neurological exam looking for dysmorphic features, developmental testing, and targeted testing depending on exam findings which may provide clues to the underlying condition. Investigations help identify genetic, structural, metabolic, and endocrine etiologies.

1. Approach to
Developmental Delay
Dr. Nagendra Chaudhary
MD Pediatrics (AIIMS, New Delhi)

2. Global developmental delay (GDD)
 delay in 2 or more domains (gross motor, fine motor, language,
cognitive and social) of development (often delayed in all
domains)
 GDD is reserved for children less than 5 years of age

3. Causes of GDD

4. Categories Causes
Prenatal Genetic
• Chromosomal: Trisomy 21, Prader–Willi syndrome Syndromic single gene: Fragile X syndrome
• Metabolic: Phenylketonuria, galactosemia, urea cycle disorders Cerebral malformations: neuronal migration
disorders
• Gene disorders: Rett disease, tuberous sclerosis, Duchenne muscular dystrophy
Acquired
• Nutritional: maternal phenylketonuria, iodine deficiency Infection (rubella, toxoplasmosis, cytomegalovirus, HIV)
• Stroke
Unknown causes (most likely genetic but can be acquired)
• Multiple congenital anomaly and mental retardation
Perinatal Birth asphyxia Infection (HSV encephalitis or Gr. B streptococcus meningitis)
Stroke (embolic or hemorrhagic) Very low birth weight, extreme prematurity
Metabolic (hypoglycemia, hyperbilirubinemia)
Postnatal-
environmental
Toxins (e.g., lead) Infection (e.g., Haemophilus influenzae b meningitis, arbovirus encephalitis)
Stroke Poor nutrition
Poverty Hypothyroid
Undetermined Familial Non-familial

5. Approach to GDD:
• Detailed medical and developmental history, including prior diagnostic testing, especially
newborn screening tests
• Prenatal history: any complications during pregnancy; prenatal diagnosis (Down syndrome
diagnosed by triple testing and increased nuchal thickness diagnosed by prenatal
ultrasonography); infections during pregnancy (TORCH infection); maternal alcohol intake (fetal
alcohol syndrome)
• Birth history: complications; APGAR score; infections (group B Streptococcus); seizures
(metabolic, hypoxic or meningitis)
• Evidence of regression (this may be a clue to inborn error of metabolism or neurodegenerative
process)
• Three-generation family history

6. Approach to GDD:
• Family history of developmental delay, consanguinity, genetic abnormalities,
syndromes etc should be inquired
• Complete physical (dysmorphism) and neurological examination
• Consider EEG testing if history concerning for epileptic seizures or
encephalopathy
• Developmental assessment: Use of screening tools like Denver or Bayley scales
• Consider psycho-educational testing, vision testing, and hearing testing
• Consider referral to a clinician with relevant expertise if child appears to have an
unrecognized genetic syndrome

7. Examination findings:
Physical examination in important in the assessment of GDD which may
provide clues as to the cause of developmental delay

8. Anthropometric examination
Microcephaly Rett disorder
Macrocephaly Hydrocephalus, Alaxander syndrome
Short stature Turner syndrome, Williams syndrome, mucolipidoses,
mucopolysaccharidoses, cretinism
Obesity Prader Willi syndrome, Bardet Biedl syndrome

9. General physical and systematic examination
Eyes Cataracts Galactosemia, rubella (gestational)
Cherry-red spot in
macula
Tay–Sachs disease
Chorioretinitis CMV infection, rubella
Dislocated lenses Homocystinuria
Glaucoma Lowe’s syndrome, Sturge–Weber syndrome
Photophobia Hartnup’s disease, homocystinuria
Retinitis pigmentosa Ataxia-telangiectasia, Bardet Biedl syndrome, mitochondrial
encephalomyopathies
Brushfield spots Down syndrome
Lisch nodules Neurofibromatosis
Hypotelorism Phenylketonuria
Hypertelorism Fetal hydantoin syndrome

10. General physical and systematic examination
Ears Conduction deafness Hurlers syndrome, Hunter syndrome
Head and
neck
Flat occiput Down syndrome, Zellweger syndrome
Prominent occiput Trisomy 18
Craniosynostosis Crouzon syndrome,
Mid face hypoplasia Down syndrome
Round facies Prader Willi syndrome
Large ears Fragile X syndrome
Malformed pinna Treacher Collins syndrome
Micrognathia Pierre Robin syndrome
Macroglossia Beckwith- Wiedemann syndrome
Webbed neck Turner syndrome

11. General physical and systematic examination
Skin Cafe´ au lait spots Ataxia-telangiectasia, neurofibromatosis, tuberous sclerosis
Rash Biotinidase deficiency, holocarboxylase synthetase deficiency
Eczema Phenylketonuria
Ash leaf macules Tuberous sclerosis
Hair Friable and tufted hair Kinky hair disease (Menkes’ disease)
Extremities Clinodactayly Down syndrome
Simian crease Down syndrome

12. General physical and systematic examination
Abdomen Hepatosplenomegaly Gaucher’s disease, Glycogen storage disease types I and III, GM1
gangliosidosis (generalized), mucopolysaccharidoses,
Blood Metabolic Acidosis Maple syrup urine disease, mitochondrial encephalomyopathies
Gait Ataxia Ataxia-telangiectasia
Odour Special odour Maple syrup urine disease, phenylketonuria
Genitourinary Large testes Fragile X syndrome
Hypogonadism Prader Willi syndrome

13. Investigations:
• Genetic syndrome: single gene tests
• Karyotyping: chromosomal abnormalities
• FISH assay: micro deletions
• Structural abnormality: MRI, MRS
• Metabolic disorder: screening tests (glucose, electrolytes, serum lactate, ammonia, liver function tests,
pyruvate, uric acid, amino acid, organic acid, acylcarnitine, creatine phosphokinase (These screening
tests are done by metabolic panels- eg: GCMS and TMS)
• Endocrine: Thyroid function tests (T4, TSH)
• EEG: if seizures
• Microarray, if possible

15. THANK YOU