9-Microcephaly- MR

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 individual’s 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

Microcephaly: Types...• Secondary (non-genetic): 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

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

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

• 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

Etiology...

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 bisyllables

– Social: mother regard, social smile, stranger anxiety, waving bye, parallel play, indicating toilet needs

Evaluation - Examination

• Head circumference: plotted on centile charts

• Cutaneous markers-café 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

• Psychometric testing

Syndromes with Mental Retardation

Side profile of a boy with fragile-X syndrome Down syndrome

Adenoma Sebaceum

Ash Leaf Macule

Hypothyroidism

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, arachnodactyly, hemiparesis

suggests homocystinuria (HCU)

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 recurrence-Downs/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