Microcephaly is a head circumference more than 3 standard deviations below the mean. It can be primary/genetic due to defects in cellular migration, neurulation or prosencephalization. Secondary microcephaly has prenatal causes like infections, drugs or postnatal causes like birth injuries or infections. Primary microcephaly is usually autosomal recessive and presents with distinctive facial features and severe intellectual disability. Secondary microcephaly has a varied presentation depending on the cause. Evaluation involves examining for dysmorphism, neurological problems and investigating for possible causes. Treatment focuses on managing symptoms while prevention centers around screening for infections and nutritional supplementation.

1. MICROCEPHALY
AND OTHER CONGENITAL ABNORMALITIES OF SKULL
- Dr. Anusha Kattula, DNB(paediatrics),
St.Philomena’s hospital, Bangalore

2. 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

8. • PRIMARY MICROCEPHALY
• Genetic
• Defective cellular migration
• Defective neurolation
• Defective prosencephalisation
• Syndromes

9. 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

10. 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

11. PRIMARY MICROCEPHALY SECONDARY MICROCEPHALY

12. • 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

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

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

15. 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

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

17. 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

18. • 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)

19. • 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)

20. • Scars
• Shape of head
• Differentiate from craniosynostosis
microcephaly craniosynostosis
Shape 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

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

22. • 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

23. • Urine and blood aminoacid levels
• Thyroid screening tests

24. • TREATMENT
• Specific treatable causes- treated
• Nutritional supplements
• Drugs to control seizures, hyperactivity and other neuromuscular
symptoms
• Genetic counselling

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

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

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

28. • 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

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

31. • 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

32. • 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

33. • Maternal serum alfa fetoprotein
• USG- BPD measurement

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

36. • HOLOPROSENCEPHALY
• Defective cleavage of forebrain

37. • 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

38. • 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

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

40. • 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

43. • 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

44. • Colpocephaly- abnormal enlargement of occipital horns of ventricles

45. • 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

46. • 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

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

48. IDENTIFY THE SYNDROMES

49. 1
• Abnormal rounding of occipital and frontal lobes
• Small cerebellum
• Narrow superior temporal gyrus
• Propensity for alzheimers
• Abnormalities of cerebral cortex

51. DOWNS SYNDROME
Incidence= 1/800

52. 2
• Microstomia
• Micrognathia
• Low set malformed ears
• Prominent occiput
• Rocker bottom foot
• Congenital heart disease
• Increased gyri
• Heterotopia of neurons

54. EDWARD SYNDROME
incidence-1/6500

55. 3
• Round facies
• Prominent epicanthal folds
• Low set ears
• Hypertelorism
• Characteristic cry

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

58. 4
• Prenatal and postnatal growth delay
• Synoprhys
• Thin down turning upper lip
• Proximally placed thumb

60. Cornelia de lange syndrome

61. 5
• Beaked nose
• Downward slanting of palpebral fissures
• Epicanthic folds
• Short stature
• Broad thumbs and toes

63. Rubinstein taybi syndrome

64. 6
• Ptosis
• Scapocephaly
• Inner epicanthic folds
• Anteverted nostrils
• Low birth weight
• Marked feeding problems

66. Smith-lemli-opitz syndrome

67. IDENTIFY THE INFECTION

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

69. cytomegalo virus

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

71. Rubella

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

73. Toxoplasmosis

74. ABNORMAL SKULL SHAPES
• Craniosynostosis- premature fusion of cranial sutures
• Decreased brain growth
• Cephalic index= maximum cranial length 100
maximum cranial width

76. IDENTIFY THE SKULL ABNORMALITIES

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

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

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

84. • 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

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

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

89. 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