An approach to a chil with microcephaly

An approach to a child with An approach to a child with microcephalymicrocephaly

Dr.Anita LamichhaneDr.Anita Lamichhane

MD Resident (paediatrics)MD Resident (paediatrics)

Shaikh Zayed Hospital Shaikh Zayed Hospital

LahoreLahore

MicrocephalyMicrocephaly

A child whose head circumference is more than A child whose head circumference is more than

three standard deviations below the mean for three standard deviations below the mean for

age and sexage and sex

Normal head circumference at birthNormal head circumference at birth

Male: 35cm(mean) range = 32---37 cm Male: 35cm(mean) range = 32---37 cm Female: 34cm(mean) Female: 34cm(mean)

Rate of growth of head circumferenceRate of growth of head circumference

2cm/month 12cm/month 1stst three months of life three months of life 1cm/month 4-6 months of age1cm/month 4-6 months of age 0.5cm/month 6-12 months of age0.5cm/month 6-12 months of age 47cm at 1 yr of age47cm at 1 yr of age 49 cm at 2 yrs of age49 cm at 2 yrs of age

HC reflects brain volume, a small skull reflects a small brain.HC reflects brain volume, a small skull reflects a small brain.

Incidence of moderate to severe mental retardationIncidence of moderate to severe mental retardation

HC from 2-3 SD below the age is 33%.HC from 2-3 SD below the age is 33%. HC > 3 SD, incidence is 62%HC > 3 SD, incidence is 62%

Not always associated with mental retardationNot always associated with mental retardation

types of microcephalytypes of microcephaly

Primary microcephaly Primary microcephaly (genetic)(genetic)

primary defect in brain primary defect in brain developmentdevelopment

prenatal onsetprenatal onset postnatal onsetpostnatal onset

Secondary microcephaly (non Secondary microcephaly (non genetic /acquired)genetic /acquired)

prenatal onsetprenatal onset postnatal onsetpostnatal onset

Causes of microcephalyCauses of microcephaly

Primary microcephaly ( genetic)Primary microcephaly ( genetic)

Prenatal onset Prenatal onset chromosomal anomalieschromosomal anomalies

Down syndrome (21 trisomyDown syndrome (21 trisomy))

Edward syndrome (18 trisomyEdward syndrome (18 trisomy

Patau syndrome (13 trisomyPatau syndrome (13 trisomy ))

malformationsmalformations

HoloprosencephalyHoloprosencephaly

LissencephalyLissencephaly

Contd.Contd.

malformation syndromemalformation syndrome

de Lange syndromede Lange syndrome

hereditary conditionshereditary conditions

Autosomal recessive ( familial)Autosomal recessive ( familial) Autosomal dominantAutosomal dominant

Post natal onsetPost natal onset

malformation Syndromesmalformation Syndromes

Aicardi syndromeAicardi syndrome

Angel man syndromeAngel man syndrome

Fanconi syndromeFanconi syndrome

Rubinstein Taybi syndromeRubinstein Taybi syndrome

Contd…Contd…

Prader-willi syndromePrader-willi syndrome

Beckwith wiedemann syndrome Beckwith wiedemann syndrome

Bloom syndromeBloom syndrome

Cri-du-chat ( 5P )Cri-du-chat ( 5P )

Secondary microcephaly Secondary microcephaly (nongenetic /acquired)(nongenetic /acquired)

Prenatal onsetPrenatal onset

Intrauterine TORCH infectionIntrauterine TORCH infection

Fetal alcohol syndromeFetal alcohol syndrome

Maternal phenylketonuriaMaternal phenylketonuria

Contd…Contd…

Post natal onsetPost natal onset

perinatal asphyxia with resultant HIEperinatal asphyxia with resultant HIE

perinatally acquired herpes simplex perinatally acquired herpes simplex encephalitis/meningitisencephalitis/meningitis

head injuryhead injury

endocrine anomaliesendocrine anomalies

hypothyroidismhypothyroidism hypopitutarismhypopitutarism

inherited metabolic disease such as PKUinherited metabolic disease such as PKU

Congenital CNS anomaliesCongenital CNS anomalies

Agenesis of the cerebellar vermisAgenesis of the cerebellar vermis

Agenesis of the corpus callosumAgenesis of the corpus callosum

EncephaloceleEncephalocele

MacrogyriaMacrogyria

PorencephalyPorencephaly

SchizencephalySchizencephaly

Others…..Others…..

HyperthermiaHyperthermia

RadiationRadiation

MalnutritionMalnutrition

DrugsDrugs

Fetal hydantoin syndromeFetal hydantoin syndrome

pathogenesispathogenesis

Occurs as a result of Occurs as a result of

Small brain & poorly growing skull Small brain & poorly growing skull

An abnormal neuronal migration during fetal An abnormal neuronal migration during fetal development. development.

Cytoarchitectural derangements.Cytoarchitectural derangements.

heterotopias of neuronal cells.heterotopias of neuronal cells.

Microcephaly VeraMicrocephaly Vera

an Autosomal recessive disorderan Autosomal recessive disorder

severe hypoplasia of the frontal regions of the brain and skull. severe hypoplasia of the frontal regions of the brain and skull.

severe mental retardation. severe mental retardation.

NoteNote:: HC alone should never be used to establish a prognosis for HC alone should never be used to establish a prognosis for intellectual development.intellectual development.

Aicardi SyndromeAicardi Syndrome

females onlyfemales only

agenesis of the corpus agenesis of the corpus callosumcallosum

infantile Spasms infantile Spasms

Severe mental & Severe mental & development retardationdevelopment retardation

seizures seizures

gray matter heterotopias.gray matter heterotopias.

Bloom SyndromeBloom Syndrome

Autosomal recessiveAutosomal recessive

MicrocephalyMicrocephaly

short stature short stature

DNA fragilityDNA fragility

a butterfly shaped facial rash. a butterfly shaped facial rash.

prone to develop Cancer. prone to develop Cancer.

Genetic diagnosis is available.Genetic diagnosis is available.

Down's SyndromeDown's Syndrome

Trisomy 21 Trisomy 21

Microcephaly. Microcephaly.

up slanting Fissures, up slanting Fissures,

epicanthal Folds, epicanthal Folds,

flat facial profile, flat facial profile,

small low set ears and small low set ears and

incurving of the fifth finger. incurving of the fifth finger.

a single palmar crease ( simian a single palmar crease ( simian crease)crease)

hypotoniahypotonia

A child with Down SyndromeA child with Down Syndrome

Edward syndromeEdward syndrome Trisomy 18Trisomy 18

MicrocephalyMicrocephaly

Prominent occiputProminent occiput

MicrognathiaMicrognathia

Narrow foreheadNarrow forehead

Cleft lip and palateCleft lip and palate

Low set earsLow set ears

ASD & VSDASD & VSD

Cri-Du-Chat SyndromeCri-Du-Chat Syndrome

MicrocephalyMicrocephaly

shrill cat like cryshrill cat like cry

High arch palateHigh arch palate

small chin small chin

Rubinstein taybi syndromeRubinstein taybi syndrome

Mental & growth retardationMental & growth retardation

Broad thumbs with talpismBroad thumbs with talpism

Microcephaly with Microcephaly with

mandibular & maxillary mandibular & maxillary hypoplasia hypoplasia

anteverted nose &anteverted nose &

antemongoloid slant to antemongoloid slant to palpebral fissurespalpebral fissures

Cornelia de Lange syndromeCornelia de Lange syndrome

Mental & growth retardationMental & growth retardation

SynophrysSynophrys

MicrognathiaMicrognathia

ASD & VSDASD & VSD

Patau syndromePatau syndrome

Trisomy 13Trisomy 13

MicrocephalyMicrocephaly

Cutis aplasia ( scalp defect )Cutis aplasia ( scalp defect )

Eyes Eyes cataractcataract ColobomataColobomata MicrophthalmiaMicrophthalmia corneal opacitiescorneal opacities

HandsHands

polydactylypolydactyly

PhenylketonuriaPhenylketonuria Deficiency of phenylalanine hydroxylase in the liverDeficiency of phenylalanine hydroxylase in the liver Accumulation of phenylalanine in the blood Accumulation of phenylalanine in the blood

Toxic to brainToxic to brain Causes Causes microcephalymicrocephaly mental retardationmental retardation cerebral palsycerebral palsy eczemaeczema mousy odor of urinemousy odor of urine

Contd…Contd…

Diagnosed by increased serum phenylalanine in Diagnosed by increased serum phenylalanine in

BloodBlood

Guthrie test ( 5Guthrie test ( 5thth– 15– 15thth day of life) day of life)

Treatment A diet low in phenylalanineTreatment A diet low in phenylalanine

How to approach a How to approach a childchild

with microcephalywith microcephaly

HistoryHistory

Family history (for genetic cause)Family history (for genetic cause)

Exposure of radiation during pregnancyExposure of radiation during pregnancy

Maternal drug historyMaternal drug history

Infection during pregnancyInfection during pregnancy

Maternal DM or PKUMaternal DM or PKU

Contd..Contd.. Difficult delivery: Difficult delivery:

forceps delivery, forceps delivery,

meconium stained liquormeconium stained liquor

cord around the neck cord around the neck

and low Apgar Scores all raises the possibility of hypoxic and low Apgar Scores all raises the possibility of hypoxic ischemic encephalopathyischemic encephalopathy

Significant fever during neonatal periodSignificant fever during neonatal period

h/o h/o high-pitched cryhigh-pitched cry

poor feeding poor feeding

seizures seizures

increased movement of the arms increased movement of the arms and legs (spasticity) and legs (spasticity)

ExaminationExamination

Introduction of oneself to the parentsIntroduction of oneself to the parents

Size of the parents & other siblings head circumferenceSize of the parents & other siblings head circumference

Note the child’s alertnessNote the child’s alertness

Look for any Dysmorphic featureLook for any Dysmorphic feature

( intrauterine TORCH, de Lange, ( intrauterine TORCH, de Lange, Rubinstein Taybi)Rubinstein Taybi)

Child’s posture & symmetry of the movementsChild’s posture & symmetry of the movements

( voluntary & involuntary )( voluntary & involuntary )

Inspect the skin for neurocutaneous stigmata Inspect the skin for neurocutaneous stigmata

Head circumferenceHead circumference

Height & weight & plot in the centile chartHeight & weight & plot in the centile chart

Note the child’s overall growthNote the child’s overall growth

generally small generally small

only head smallonly head small

examine the head for any scar marksexamine the head for any scar marks

( surgical repair of Craniosynostosis, ( surgical repair of Craniosynostosis, closure of Encephalocele) closure of Encephalocele)

Contd..Contd..

Shape of the head Shape of the head

flat occiput of Autosomal recessive flat occiput of Autosomal recessive microcephaly microcephaly

Palpate the head for ridging along the suture line & any deformity of Palpate the head for ridging along the suture line & any deformity of skull contourskull contour

(Craniosynostosis) or bony defects ( repaired (Craniosynostosis) or bony defects ( repaired Encephalocele) Encephalocele)

Anterior fontanelleAnterior fontanelle a large AF occurs in a large AF occurs in

trisomiestrisomies

congenital rubellacongenital rubella

hypothyroidism hypothyroidism

Petechiae or skin rash Petechiae or skin rash

Eye Eye

micropthalmos micropthalmos (TORCH)(TORCH)

lens for cataract (lens for cataract (TORCH, trisomiesTORCH, trisomies ) )

fundus for chorioretinitis (fundus for chorioretinitis (TORCH)TORCH)

glaucomaglaucoma ( congenital rubella )( congenital rubella )

red reflex red reflex ( rubella)( rubella)

hypotelorismhypotelorism (Holoprosencephaly)(Holoprosencephaly)

upward slant upward slant ( ( down syndrome)down syndrome)

epicanthi fold epicanthi fold ( trisomies )( trisomies )

squintsquint ( TORCH)( TORCH)

pupils for anisocoria pupils for anisocoria ( cong. Varicella ) ( cong. Varicella )

Ears for hearingEars for hearing

impairment ( TORCH )impairment ( TORCH )

neck for goiterneck for goiter

hypothyroidismhypothyroidism

Systemic examinationSystemic examination

CVSCVS for congenital heart defects ( congenital rubella,trisomies )for congenital heart defects ( congenital rubella,trisomies )

AbdomenAbdomen

hepatosplenomegaly (TORCH)hepatosplenomegaly (TORCH)

GenitaliaGenitalia

micropenis with hypopitutarism structure ( cryptorchidism)micropenis with hypopitutarism structure ( cryptorchidism)

Joint contracturesJoint contractures

Asses the gross and fine motor developmentAsses the gross and fine motor development– 180 degree maneuver– 180 degree maneuver

InvestigationsInvestigations

Serological tests for intrauterine TORCH infectionSerological tests for intrauterine TORCH infection

Chromosomal analysis for Autosomal Trisomy syndromeChromosomal analysis for Autosomal Trisomy syndrome

Neonatal screening tests for PKU & congenital hypothyroidismNeonatal screening tests for PKU & congenital hypothyroidism

Urine testUrine test

Metabolic screening to detect virus Metabolic screening to detect virus excretion with CMVexcretion with CMV

CSFCSF

to detect intrauterine or perinatal TORCH to detect intrauterine or perinatal TORCH infectioninfection

a)a) Skull x raySkull x ray for cerebral calcificationfor cerebral calcification

CMV --- periventricularCMV --- periventricular

Toxoplasmosis—diffuseToxoplasmosis—diffuse

to detect early closure of suturesto detect early closure of sutures

CT SCAN/ MRICT SCAN/ MRI

for cerebral malformationsfor cerebral malformations

evidence of perinatal asphyxia or evidence of perinatal asphyxia or intrauterine infectionintrauterine infection

Genetic studies are indicated in patientsGenetic studies are indicated in patients

with Dysmorphic featureswith Dysmorphic features

Microcephaly may be diagnosed before birth Microcephaly may be diagnosed before birth by prenatal ultrasound.by prenatal ultrasound.

Genetic counseling should be doneGenetic counseling should be done

ManagementManagement

No treatment for microcephalyNo treatment for microcephaly

Baby’s head cannot be returned to a normal size & shapeBaby’s head cannot be returned to a normal size & shape

Includes focusing on preventing or minimizing deformities & Includes focusing on preventing or minimizing deformities & maximizing the child’s capabilities at home & in the community.maximizing the child’s capabilities at home & in the community.

Contd..Contd..

According to the cause.According to the cause.

AnticonvulsantsAnticonvulsants

PhysiotherapyPhysiotherapy

Hearing & speech therapyHearing & speech therapy

Dietary management for failure to Dietary management for failure to thrive thrive

Genetic counseling Genetic counseling