Microcephaly

Dr Yog Raj Khinchi

Normal Infant Skull

Flexible enough to get through vagina Molding

Expansile enough to accommodate rapid brain growth

HEAD GROWTH GUIDELINES

2 cm every month during 0-3 mo 1 cm every month during 3-6 mo 0.5 cm every month during 6-12 mo OFC (HC) : In term normal baby At birth:35cm 3mo: 41 cm 6mo: 44 cm 1yr: 47 cm 2 yr: 48 cm Adult: 52-55 cm

HC : Post natal percentiles

Microcephaly: Definition
Microcephaly denotes an occipitofrontal circumference (OFC) 3 or more standard deviations below the mean for the individuals age and gender.

Craniosynostosis - results from premature fusion of 1 or more sutures results in a small head size with abnormal head shape which should be distinguished from microcephaly.

HEAD GROWTH DEFINITIONS

Term infant <32 cm microcephaly > 38 cm macrocephaly Macrocephaly - excessive head size 2 SD

Microcephaly
OFC < 32 cm at birth If OFC < 10 percentile- high risk of Learning Disabilities If OFC < 3 percentile- near 100% risk of decreased IQ Primary Microcephaly Secondary Microcephaly

Microcephaly: Types
Primary (genetic)
Familial:
AD mild forehead slant, prominent ears and borderline MR AR typical appearance with slanted forehead, prominent nose and ears, severe MR

Genetic syndromes:

Down and other trisomies Cri-du chat syndrome Cornelia de Lange syndrome Rubinstein-Taybi syndrome - Anatomical defects in developing

brain

 Secondary (non-genetic):

Microcephaly: Types...
If noxious agent affects brain growth in utero and upto 1st 2 years of life.
Hypoxic-ischaemic encephalopathy Intrauterine infections (TORCH) HIV CNS infections ICH Fetal hydantoin syndrome (phenytoin in pregnancy) Fetal alcohol syndrome Malnutrition Metabolic (maternal PKU) Craniosynostosis

Microcephaly

Depending on the severity of the accompanying syndrome, children with microcephaly may have
Mental retardation, Delayed motor functions and speech, Facial distortions, Short stature, Hyperactivity, Seizures, Difficulties in coordination & balance, Other neurological abnormalities.

Microcephaly

Microcephaly

Child with secondary microcephaly following HIE

Evaluation - History
Antenatal history-maternal hyperthermia, exposure to radiation, exanthematous febrile illness Family history of small head/MR/seizures. OFC at birth Post natal CNS infections particularly in first 2 years of life.

Measuring OFC
A fibroelastic / metal measuring tape is placed around the head at the following points:

Occipital protuberance posteriorly Nasion anteriorly Measurement is made by cross tap technique over the temporal bone.

Examination
OFC-plotted in a chart and compared for the norms (age and sex). Serial OFC records desirable-rate of growth Abnormal head shape, fontanelle & sutures Stigmata of intrauterine infections Dysmorphism Detailed neurological examination

Investigations
Neuroimaging - CT/MRI of the brain help identify structural defects. TORCH titers for intrauterine infections Karyotype if chromosomal syndrome/ associated congenital malformation Maternal phenylalanine levels (for PKU) Fetal USG-for fetal head size particularly if family history present

Treatment
Per se head size cannot be changed by treatment

Associated delay needs to be addressed Stimulation programme Special schools

Treatment of hearing/vision impairment if present

Treatment of seizures if present

Mental Retardation (MR)

Definition
MR is characterized by significant below average intellectual functioning (IQ<70) concurrently with limitation in two or more adaptive skills viz., Communication Self-care Home living Social skills Community use Self-direction Health and safety Functional academics Leisure and work It manifests before 18 years. Formal psychometric test is required to make the diagnosis

Developmental delay
Global developmental delay -child < 5 years age with DQ<70 in 2 or more developmental domains.

The various domains of development include: gross motor, fine motor, language and social

DQ

developmental age x 100 chronological age

How common is it?

Occurs in about 2.5 % of individuals. Mild (8-9 times more common) Moderate Severe

Etiology
Specific diagnosis that will provide information about Prognosis Recurrence risks Preferred modes of available therapy Prenatal, perinatal or post natal

Etiology...
Prenatal
Genetic syndromes-Downs, fragile-X Congenital hypothyroidism IEM TORCH infections/chorioamnionitis Endogenous/exogenous toxins in mother during pregnancy Congenital malformation of CNS Prematurity / hypoplastic SGA

Perinatal
Trauma/HIE

Etiology...
Postnatal
Hypothyroidism (congenital / juvenile) Acquired postnatal CNS infection/trauma PEM, deficiency of iodine/iron /zinc Exogenous toxin: lead Neurocutaneous syndromes: NF,TS Neuromuscular disorders with CNS involvement Neurodegenerative disorders may have a progressively worsening course Idiopathic: largest group in mild MR

Evaluation: History
Ethnic origin /consanguinity Family h/o MR, dev delay, epilepsy, neurological deficit Gestational history Time and mode of delivery, requirement of resuscitation Developmental milestones School performance

Developmental milestones
Milestones refer to the time of achievement of a particular developmental skill. Questions systematically elicited in all 4 domains Gross motor: head holding, roll over, sit with and without support, stand with and without support, walk, run, go up & down stairs, hop, skip Fine motor: reaching out for objects, grasp, transfer of objects from hand to hand ,feeding & writing skills Language: cooing, squealing, vowels ,consonants, non-specific & specific

Evaluation - Examination
Head circumference: plotted on centile charts Cutaneous markers-caf au lait spot, ash leaf macule, adenoma sebaceum Dysmorphism: large ears, long face, prominent lower jaw in fragile-X syndrome Detailed neurologic examination including eye

Syndromes with Mental Retardation

S id e p ro file o f a b o y w ith fra g ile -X sy n d ro m e

D ow n sy n d ro m e

Adenoma Sebaceum

Ash Leaf Macule

CT Scan Tubers

CT Scan Tubers

H y p o th y ro i d ism

Grades / Severity of MR
Borderline (IQ:70-80): independent; employable Mild (IQ: 50-69): educable Moderate (IQ:35-49): trainable Severe/profound: dependent on caretakers

Investigations
Screening for hypothyroidism-TSH / T4 Fragile-X molecular tests. Neuroimaging-not mandatory;picks structural defects, neurodegenerative Karyotype-if dysmorphic,other congenital malformations Screening for inborn errors of metabolism if clues on evaluation Intermittent/progressive deterioration, seizures, fresh neurodeficits Light pigmentation, photosensitivity, athetoid ,small OFC suggests phenylketonuria (PKU) Lens dislocation, tall stature,

Treatment
Rehabilitation Borderline /mild MR can be integrated with normal schools Moderate MR would need special schooling ;vocational training to achieve independence

Treatment of co-morbidities: seizures, behavioral problems

Treat for hypothyroidism

Treatment...
PKU-special diet; HCU-pyridoxine, folate

Genetic counseling / prevent recurrenceDowns/Fragile-X karyotype /molecular genetics in affected child Explaining risk of recurrence based on inheritance Prenatal diagnosis to know if fetus affected and termination if the couple so desires