MICROCEPHALY

AND OTHER CONGENITAL ABNORMALITIES OF SKULL

- Dr. Anusha Kattula, DNB(paediatrics),

St.Philomena’s hospital, Bangalore

What is microcephaly?

• Definition- head circumference more than 3 standard deviations below the mean for age and sex (Nelson)• Classified as• 1)PRIMARY/ GENETIC• 2)SECONDARY/ NON GENETIC

• PRIMARY MICROCEPHALY

• Genetic • Defective cellular migration• Defective neurolation• Defective prosencephalisation• Syndromes

SECONDARY MICROCEPHALY

PRENATAL• Maternal intake of drugs• Maternal illnesses- toxemia,

diabetes,CRF, phenyl ketonuria• Intrauterine infections-

CMV,rubella, toxoplasma• Radiation• Migrational defects

POSTNATAL• Perinatal insults(e.g. birth asphyxia)• Inborn errors of metabolism- phenyl

ketonuria• CNS insults- encephalitis, meningitis,HSV• HIV infection, malnutrition• Rett syndrome• Trauma• Endocrine-hypothyroid and

hypopituitarism• Metabolic-hypoglycemia,PKU

PRIMARY MICROCEPHALY

• Low crown, receeding forehead.occipital flattening,wrinkling of skin

• Present since birth

SECONDARY MICROCEPHALY

• Small head

• May be present at birth/evident later

PRIMARY MICROCEPHALY SECONDARY MICROCEPHALY

• GENETIC- MICROCEPHALY VERA• Familial and autosomal dominant are most common• 1) Autosomal recessive( familial)- incidence-1/40000 slanted forehead, prominent nose and ears severe MR(non progressive), prominent seizures Brain is small with small cerebral cortex

AUTOSOMAL DOMINANT• Rare non distinctive facies- upslanting palpebral fissures, hypertelorism slanting forehead(mild),prominent ears, short stature, receeding forehead,

• Mild intellectual impairment• Neurosonogram- normal• MRI- abnormal development of brain, small cerebellar and cerebral

hemispheres and pachygyria

AUTOSOMAL RECESSIVE AUTOSOMAL DOMINANT

inheritance Inherits abnormal gene from both parents

Inherits abnormal gene from one of the parents

phenotype Typical appearance with slanted forehead,prominent nose and ears

Non distinctive facies

seizures Prominent readily controlled

Mental retardation severe Mild to moderate

2) Syndromes• Downs syndrome• Edwards syndrome• Cri-du-chat syndrome• Cornelia de lange syndrome• Rubinstein taybi syndrome• Smith-lemli-optiz syndrome

How to approach?

• An 18 month old boy is brought to OPD. Parents are concerned that the boy’s head is small. They also note that he is not walking as well as his older brother did at this age.

• The head circumference is found to be 3 SD below the normal for that age

• Family history- to r/o primary• h/o prenatal,perinatal and postnatal insults• Exposure of radiation during pregnancy• Maternal drug history• Infections/DM/PKU• Difficult delivery/MSAF/low apgars• Significant fever in neonatal period• h/o high-pitched cry/ poor feeding/ seizures/ increased movement

of the arms and legs (spasticity)

• EXAMINATION• HC of the parents and siblings• Serial HC records• Look for dysmorphic features• Child’s posture & symmetry of the movements• Inspect the skin for neurocutaneous stigmata • Overall growth( height and weight centiles)

• Scars • Shape of head• Differentiate from craniosynostosis

microcephaly craniosynostosisShape of skull normal abnormal

Prominent bony ridge absent common

Xray Minimal suture line No sutural line

CT scan sutures Sutures fused

Sutural line normal ridged

ICP normal May be increased

• Detailed neurological evaluation including fundus• Developmental examination- evidence of delay or regression

• INVESTIGATIONS• Screening for infections• Xray skull- to determine suture patency, overriding, fusion and

calcification• CT – calcifications• MRI- structural abnormalities of brain• Karyotype- if dysmorphism/ other malformations• Phenylalanine levels in mother

• Urine and blood aminoacid levels• Thyroid screening tests

• TREATMENT• Specific treatable causes- treated• Nutritional supplements• Drugs to control seizures, hyperactivity and other neuromuscular

symptoms• Genetic counselling

• PREVENTION• Preventing child birth after 35 years• Screening for TORCH• Thyroid screening in newborn• Adequate nutrition• Health education• Genetic counselling

• RECURRENCE RISK• Familial microcephaly- on inheritance pattern(25-50%)• If no cause identified-empirical risk-6%• Maternal USG serially starting in early pregnancy

• DEFECTIVE NEURULATION• 1st week- rostrocaudal axis• 3rd and 4th week- neural plate- tube• Anterior neuropore- closes by 24th day

• ANENCEPHALY-• Defective closure of anterior neuropore• Defect in calvarium, meninges and scalp• Rudimentary brain- hind brain, diencephalon• a/w folding of ears, cleft palate, CHD• 1/1000• Recurrence 4%, 10% if 2 previous affected

• Nutritional and vitamin deficiencies• Environmental and social factors• Antenatal – amniocentesis, AFP levels• USG between 14th and 16th weeks

• ENCEPHALOCELE• Protrusion of cortex and meninges through cranium bifidum• Midline occipital – most common• Hydrocephalus• Sessile base- cerebral tissue• Transillumination• Xray skull and cervical spine• USG

• MRI/CT- accurate• Vision problems,microcephaly,MR and seizures• Meckel-gruber syndrome• AR• Occipital encephalocele, cleft lip or palate, microcephaly,• Micropthalmia, abnormal genitalia, polycystic kidneys, polydactyly

• Maternal serum alfa fetoprotein• USG- BPD measurement

• DEFECTIVE PROSENCEPHALIZATION• Forebrain develops from midline vesicle- 25-30 days gestation• 30-40 days gestation- cerebral vesicles(bilateral)

• HOLOPROSENCEPHALY• Defective cleavage of forebrain

• 4th type- middle interhemispheric fusion(MIHF)/ syntelencephaly• segmental area of non cleavage• non separation of posterior frontal and parietal lobes• Autosomal dominant-7p36.2 locus• Abnormalities of chr 13• Trisomy 13 and 18

• CF - Cyclopia,synopthalmia,cebocephaly,single nostril solitary central inscisor, premaxillary agenesis• CHD, clubbing, polydactyly, syndactyly,accessory spleen, liver, malrotation• Present with hypotonia, seizures, apnea• Intellectual , motor and sensory impairment

• Diagnosis- 1/5000-1/16000• MRI• molecular genetics• Prenatal diagnosis- by USG after 10th week

• AGENESIS OF CORPUS CALLOSUM• Develops from commissural plate• Direct insult/disruption of genetic signaling• When a/w cell migration defects- mental retardation,

microcephaly,hemiparesis, diplegia and seizures

• XR/AD/AR trait• a/w trisomy 8 and 18 and metabolic disorders• Aicardi syndrome- agenesis of corpus callosum chorioretinal lacunae, coloboma infantile spasms MR, Seizures

• Colpocephaly- abnormal enlargement of occipital horns of ventricles

• DEFECTIVE CELLULAR MIGRATION• Radial glial fibre system• Lissencephaly- defective neuroblast migration• agyria, heterotopia,enlarged lateral ventricles• Type 1- complete absence of gyri• Corpus gangliothalamicus pathway not involved• Hypoplasia of optic nerve, micropthalmia

• Type 2- disorganized cluster of neurons with haphazard orientation• Miller dieker syndrome- prominent forehead, anteverted nostrils micrognathia, low set ears microdeletion of 17p13.3 Doublecortin- X chromosome gene CF- myoclonic seizures hypotonia- spasticity- opisthotonus

• Bilateral periventricular nodular heterotopia- epilepsy and normal intelligence• MRI for diagnosis

IDENTIFY THE SYNDROMES

1

• Abnormal rounding of occipital and frontal lobes• Small cerebellum• Narrow superior temporal gyrus• Propensity for alzheimers• Abnormalities of cerebral cortex

DOWNS SYNDROME Incidence= 1/800

2

• Microstomia• Micrognathia• Low set malformed ears• Prominent occiput• Rocker bottom foot• Congenital heart disease• Increased gyri• Heterotopia of neurons

EDWARD SYNDROME incidence-1/6500

3

• Round facies• Prominent epicanthal folds• Low set ears• Hypertelorism• Characteristic cry

CRI DU CHAT SYNDROME(5p-) incidence-1/50000

4

• Prenatal and postnatal growth delay• Synoprhys• Thin down turning upper lip• Proximally placed thumb

Cornelia de lange syndrome

5

• Beaked nose• Downward slanting of palpebral fissures• Epicanthic folds• Short stature• Broad thumbs and toes

Rubinstein taybi syndrome

6

• Ptosis• Scapocephaly• Inner epicanthic folds• Anteverted nostrils• Low birth weight• Marked feeding problems

Smith-lemli-opitz syndrome

IDENTIFY THE INFECTION

• Small for dates• Petechial rash• Hepatospleenomegaly• Chorioretinitis• Deafness• Mental retardation• Seizures• CNS calcification( periventricular)• microgyria

cytomegalo virus

• Growth retardation• Purpura• Thrombocytopenia• HSM,CHD• Chorioretinitis• Cataracts• Deafness

Rubella

• Purpura• HSM• Jaundice• Convulsions• Hydrocephalus• Chorioretinitis• Cerebral calcifications

Toxoplasmosis

ABNORMAL SKULL SHAPES

• Craniosynostosis- premature fusion of cranial sutures• Decreased brain growth• Cephalic index= maximum cranial length 100 maximum cranial width

IDENTIFY THE SKULL ABNORMALITIES

• DOLICHOCEPHALY- A-P length more than width boat shaped skull premature fusion of saggital suture prominent occiput, broad forehead small or absent anterior fontanelle

• BRACHYCEPHALY- coronal suture fuses prematurely -broad skull, flat forehead, decreased A-P diameter *aperts syndrome *carpenters syndrome *crouzons syndrome *downs syndrome

TRIGONOCEPHALY-metopic suture fuses prematurely narrow anteriorly, wide posteriorly keel shaped forehead and hypotelorism

• ACROCEPHALY/TURRICEPHALY-premature fusion of coronal and lambdoid sutures

-skull is abnormally high and conical in shape

- a/w syndactyly - in Crouzons disease and Pfeiffers

syndrome

• PLAGIOCEPHALY- irregular asymmetric fusion of sutures -Chotzens syndromeA) Frontal - unilateral flattening of forehead,elevation of ipsilateral orbit and eyebrow, prominent ear - premature fusion of unilateral coronal and sphenofrontal suturesB) occipital- occipital flattening and bulging of ipsilateral frontal bone -faulty positioning during infancy

• KLEEBLATTSCHADEL DEFORMITY- trilobed skull( clover leaf) -premature fusion of multiple sutures -carpenters, crouzons, aperts and pfeiffers

syndromes

Type of skull Appearance Cephalic index

Acrocephaly High tower like head, vertical forehead

>85

oxycephaly High and sloping, pointed >85

Brachycephaly Broad head, recessed lower forehead

80-85

mesocephaly Normal cranium 60-75

Dolichocephaly(scapho) Long cranium 70-75

trigonocephaly Triangular head,prominent vertical ridge

<70