A%20baby%20with%20cloverleaf%20skull%20anomaly

1
A baby with cloverleaf skull anomaly

• R 3 ???
• Supervisors Drs. ???, ??? ???

2
Admission Data

• Name ?xx?? (?xx)
• Number 3619275-6
• Sex Female
• Admission Date 94/05/30
• Chief complaints
• 1. Prematurity (GA 32 weeks)
• 2. Respiratory distress
• 3. Congenital anomaly

3
Present Illness

• Perinatal examinations at OBS/GYN Clinic did not
  show any abnormality.
• Mother was also denied of perinatal drug usage,
  infection or systemic disease.
• PROM was noted since 5/12 and tocolysis performed
  since 5/12 at OBS/GYN Clinic. Ampicillin Tx from
  5/12 and 2 doses of Decadron were given.

4
Present Illness

• Due to fetal distress (HR 80-90/min), emergency
  C/S was performed.
• The Apgar score 71 ? 95.
• After birth, bradycardia was noted and
  endotracheal tube was inserted. Under the
  diagnosis of PPROM, prematurity and respiratory
  distress, she was admitted for
• further treatment and evaluation.

5
Present Illness

• Birth history
• DOB on 94/05/30 at 2226
• EDC 94/07/20
• GA 32 weeks, BBW 1,910gm
• Via C/S due to fetal distress
• Apgar score 71?95
• PPROM noted since 05/12
• Prenatal ampicillin since 05/12
• Prenatal steroid x2 doses

6
Present Illness

• Maternal history
• G1P1 healthy mother
• No GDM, HTN, Toxemia, APH, PPH
• URI(-), Fever(-)
• HBsAg(-), HBeAg(-)

7
Family History
28 years old BG AB ???
34 years old BG AB ???
8
Physical Examination

• Blood pressure 56/37?44/29?Dopamine used?58/36
• Heart rate 116 /min
• Respiratory rate 60 /min
• Body temperature 36.3C
• General appearance acute ill looking

9
Physical Examination
Eyes not injected Ear suspect ear canal
obstruction Nose suspect left canal
Obstruction Mouth no cleft palate
Head Cloverleaf skull Frontal bone
bossing Anterior fontanel 7.5 x 4.5cm Mid-face
hypoplasia
10
Physical Examination
Frontal area bossing Pseudo low set
ears Exophthalmos
11
Physical Examination
Thorax symmetric expansion no pigeon
chest Chest breathing sound coarse No rale, no
wheezing Heart RHB, no murmur or thrill Abdomen
Soft and flat Bowel sound normactive No
hepatosplenomegaly Extremities free movable No
shortened limbs Rectum and anus patent
12
Laboratory Data (5/30)
CBC Hgb 17.9 g/dL, Hct 53.6, MCV 116.5 WBC 9,600 /uL, PLT 320,000/uL, BG B Band 0, Neut 23, Eosin 2, Baso 1 Baso 1, Monocyte 1, Lym 72 Atypical lymphocyte 1
Chemistry Dex 38 mg/dl, Na 145 mEq/L K 4.9 mEq/dl, Free Ca 1.19 mmol/L
Arterial Blood Gas PH 7.332, PaCO2 45.9 mmHg, PaO2 124.1mmHg, HCO3 23.8 mmol/L BE -2.1 mmol/L
13
Laboratory Data (5/30)
CSF Glucose 38 mg/dL, Protein 179 mg/dL RBC 58 /CMM, WBC 2 /CMM L N 0 2
???? CRP lt0.1 mg/dL, RPR non-reactive Urine GBS negative Rubella IgM 0.12 (lt0.8) HSV-1 IgM 0.39 (lt1) HSV-2 IgM 0.51 (lt1) Toxoplasma IgM 0.09 (lt0.5) CMV IgM 0.08 (lt0.5)
Immune Total IgM 9 mg/dL
14
Laboratory Data (5/30)

• CXR (5/30) Parahilar radiating congestion of
  both lungs is seen. Slight overaeration of
  bilateral lungs is seen.
• No limbs or vertebrae abnormalities
• IMP Retention of lung fluid.

15
Impression

• 1. Prematurity (GA 32 weeks, BBW 1910 gm)
• 2. PROM about 18 days
• 3. Respiratory distress, suspect RDS grade I
• 4. Hypotension
• 5. Congenital anomaly
• r/o Crouzon syndrome
• r/o Thanatophoric dysplasia
• r/o Craniosynostosis

16
Hospital Course

• Initial management
• 1. On ETT IMV
• 2. N/S challenge first, then add Dopamine
  (5/305/31)
• 3. Ampicillin and gentamicin (5/306/06) for
  suspected congenital infection

17
Hospital Course

• Brain echo (5/31) Ventricular dilatation,
  bilateral suspect pachygyria
• Renal echo (5/31) negative findings
• Abdominal echo (5/31) gall bladder is visible
  no intra-abdominal mass was noted
• Heart echo (5/31) PDA (left to right, 0.146 cm),
  PHT (56.5 mmHg), Dysarrhythmia

18
Hospital Course

• His respiratory distress improved, so
  endotracheal tube was removed and changed to O2
  hood since 6/01
• DC O2 hood on 6/07

Culture Blood culture (5/30) no growth CSF culture (5/30) no growth
Chromosome study 46, XX, normal
19
Skull PA LAT view (6/01)
Obliteration of bilateral coronal and Lambdoidal
sutures of skull is seen. Premature closure is
considered. Association with cloverleaf skull
syndrome is considered
20
Hospital Course

• Consult Ophthalmologist
• ?Incomplete regression of hyaloid vessels
• Vessels constriction of left eye
• ?Impression
• 1. Congenital abnormality of retinal vessel
  (OS)
• 2. Optic neuropathy (OS)
• ?Suggest VEP examinations after general
• condition stabilized

21
Hospital Course

• Add aminophylline since 6/02
• F/U brain echo (6/03) Ventriculomegaly,
  bilateral, symmetric Suspect pachygyria
  High RI (0.94)
• Arrange brain MRI with/without contrast
• on 6/03

22
1. Dilatation of the lateral ventricles is noted,
The 3rd ventricle is mildly dilated. Presence of
cavum septum pellucidum and cavum vergae is
noted. 2. The cerebral cortical sulci is broad
and flattened, pachygyria is considered. 3.
Brachicephaly is noted. Trilobed skull is
demonstrated on coronal images. Cloverleaf skull
syndrome due to premature closure of multiple
cranial sutures is considered. 4. The posterior
portion of the septum pellucidum is not
visualized.
94.6.3
Cavum septum pellucidum
Cavum vergae
23
Brain MRI (6/03)
24
1. The posterior fossa Is small and torcular is
low Lying. Tonsillar herniation Thru the
foramen magnum Is also noted. 2. No abnormal
enhancement is noted. 3. The pituitary gland,
cavernous sinuses and cerebellopontine angles
appear normal and symmetric.
25
(No Transcript)
26
Brain MRI (6/03)

• Impression
• 1. Cloverleaf skull syndrome, following
  anomalies including acrocephalopolysyndactylies
  (Crouzon, Pfeiffer, Carpenter, Apertetc.) and
  type II form of thanatophoric dysplasia should be
  considered in the differential diagnosis.
• 2. Dilatation of the lateral ventricles and
  presence of cavum septum pellucidum and cavum
  vergae.
• 3. Pachygyria.
• 4. Small posterior fossa and cerebellar
  tonsilar herniation.
• 5. Absent posterior septum pellucidum.

27
Brain CT (6/09)
1. Dilatation of the lateral ventricles and mild
dilatation of the 3rd ventricle are noted.
Presence of cavum septum pellucidum and cavum
vergae is noted. 2. The posterior septum
pellucidum is not visualized.
28
Brain CT (6/09)
29
Brain CT (6/09)
30
Brain CT (6/09)
1. Premature closure of multiple cranial sutures
causing trilobed appearance of skull on coronal
images and brachicephaly is seen, cloverleaf
skull syndrome is considered. Beaten copper
appearance of the skull is also noted. 2.
Enlargement of the fontanelles is noted.
31
Brain CT (6/09)

• Impression
• 1. Cloverleaf skull syndrome.
• 2. Dilatation of the lateral ventricles and
  mild dilatation of the 3rd ventricle and presence
  of cavum septum pellucidum and cavum vergae.
• 3. Absent posterior septum pellucidum.

32
Hospital Course

• Frequent bradycardia (7080/min), apnea and
  desaturation (7080) noted on 6/15
• No fever, no hypotension
• Head circumference increased from
• 27.5 cm to 29 cm
• Brain echo (6/15)
• Progressing ventriculomegaly, bilateral
• Hydrocephalus, non-communicating type
• Pachygyria, suspect lissencephaly
• High RI (1.0)

33
Hospital Course

• IICP was highly suspected, so CSF tapping was
  performed, however, reddish CSF fluid was noted
• Lab data (1)
• Lab data (2)
• CXR
• Brain CT (6/15)
• 1. Cloverleaf skull syndrome.
• 2. Dilatation of the lateral ventricles and
  mild dilatation of the 3rd ventricle and presence
  of cavum septum pellucidum and cavum vergae.
• 3. Absent posterior septum pellucidum.

34
Laboratory Data (6/15)
CBC Hgb 13.6 g/dL, Hct 40.2 WBC 10,600/uL, Platelet 313,000/uL Band 0, Neut 38, Eosin 1 Baso 0, Monocyte 8, Lym 53
???? CRP lt0.1 mg/dL
Arterial blood gas PH 7.469, PaCO2 25.7 mmHg PaO2 66.5 mmHg, HCO3 18.2 mmol/L B.E-5.5 mmol/L
35
Laboratory Data (6/16)
CSF Glucose 42 mg/dL, Protein 65 mg/dL RBC 37/CMM, WBC 1/CMM, L N 10
Chemistry Glucose 54 mg/dL, Na 141 mEq/L
Chemistry K 5.4 mEq/L, Cl 109 mEq/L, Ca 10.1 mg/dL
Coagulation PT 10.8 sec (control 11.0) APTT 39.2 sec (control 30.0), INR 0.96 (lt2)
Culture Blood culture no growth CSF culture no growth Throat rectal virus cultures no growth yet
36
CXR (6/15)

• CXR (6/15) The follow up chest condition shows
  stable as compared
• with the last exam.

37
Hospital Course

• Consult Neurosurgeon immediately
• Extraventricular device was inserted on 6/15,
  then Cefamezine for post-operation prophylaxis
  (6/166/18)
• PRBC was transfused after OP
• Luminal for preventing seizure (6/15)

38
Hospital Course

• Her bradycardia and desaturation improved a lot
  after operation
• EVD discharge 18cc (6/16)?37cc (6/17) ?22.5cc
  (6/18)?24cc (6/19)
• Brain echo (6/16) Hydrocephalus, /p V-P shunt
  Decreased ventricle size, bilateral

39
Hospital Course

• Unfortunately, her FGFR3 gene PCR showed positive
  on 6/18, so Thanatophoric dysplasia was highly
  suspected
• Very poor prognosis was told, so her family
  decided to remove EVD shunt since then
• After detailed explanation of the consequence of
  removing EVD shunt to her family, her EVD shunt
  was removed on 6/24

40
Hospital Course

• However, further genetic study had ruled out the
  possibility of thanatophoric dysplasia
• ?Newborn screen normal
• ?Tandem mass normal
• ?Sequencing of FGFR3 gene normal
• ?PCR study of FGFR2 gene pending

41
Hospital Course

• Brain echo (6/30)
• 1. Progressive bilateral ventricle dilatation
• 2. Suspect blood clot inside the ventricle,
  bilateral
• 3. Porencephaly at right fronto-parietal area,
  due to EVD
• 4. High RI (0.97)
• Brain echo (7/06)
• 1. Hydrocephalus, non-communicating type,
  progressing
• 2. Porencephaly at right fronto-parietal area,
  progressing
• 3. High RI (1.0)

42
Hospital Course (7/07)
43
Hospital Course (7/07)

• At this point, she would get bradycardia easily
  if you press on her anterior fontanel gently

44
Hospital Course (7/15)
45
Hospital Course

• This patient was discharged on 7/16
• However, she was brought back to our ER on 7/18
  without breathing heart beating
• Unfortunately, she died on 7/18

46
Discussion

1. Craniosynostosis
2. Cloverleaf skull syndrome

47
Craniosynostosis

• Primary craniosynostosis a primary defect of
  ossification
• Secondary craniosynostosis a failure of brain
  growth, more commonly
• Syndromic craniosynostosis display other body
  deformities

48
Craniosynostosis

• Simple craniosynostosis only 1 suture fuses
  prematurely
• Complex or compound craniosynostosis premature
  fusion of multiple sutures

49
Craniosynostosis

• The coronal suture separates the 2 frontal bones
  from the parietal bones.
• The metopic suture separates the frontal bones.
• The sagittal suture separates the 2 parietal
  bones.
• The lambdoid suture separates the occipital bone
  from the 2 parietal bones.
• The primary factor that keeps sutures open is
  ongoing brain growth.
• Normal skull growth occurs perpendicular to each
  suture.

50
Primary craniosynostosis

• When 1 or more sutures fuse prematurely, skull
  growth can be restricted perpendicular to the
  suture. If multiple sutures fuse while the brain
  is still increasing in size, intracranial
  pressure can increase.
• Cause a primary defect in the mesenchymal layer
  ossification in the cranial bones.
• A gene locus for single suture craniosynostosis
  has not been identified.

51
Scaphocephaly - Early fusion of the sagittal
suture
52
Ant. plagiocephaly - Early fusion of 1 coronal
suturePost. plagiocephaly - Early closure of 1
lambdoid suture
53
Brachycephaly - Early bilateral coronal suture
fusion
54
Trigonocephaly - Early fusion of the metopic
suture
55
Secondary craniosynostosis

• More frequent
• Early fusion of sutures due to primary failure of
  brain growth
• Intracranial pressure usually is normal, and
  surgery seldom is needed
• Intrauterine space constraints may play a role in
  the premature fusion of sutures in the fetal
  skull. This has been demonstrated in coronal
  craniosynostosis
• Microcephaly usually suggests a secondary
  craniosynostosis

56
Secondary craniosynostosis

• Endocrine
• Hyperthyroidism, hypophosphatemia, vitamin D
  deficiency, renal osteodystrophy, hypercalcemia,
  and rickets
• Hematologic disorders
• Which cause bone marrow hyperplasia (eg,
  sickle cell disease, thalassemia)
• Inadequate brain growth
• Microcephaly and its causes and shunted
  hydrocephalus

57
Syndromic Craniosynostosis

• Craniosynostosis sometimes is associated with
  sporadic craniofacial syndromes such as Crouzon,
  Apert, Chotzen, Pfeiffer, or Carpenter syndromes.
• In this context, facial features, typically
  craniofacial abnormalities, suture ridging, and
  early closure of fontanelles, suggest the
  diagnosis.
• Genetic mutations responsible for fibroblast
  growth factor receptors 2 and 3

58
Craniosynostosis

• Incidence in the US 0.04 0.1
• 28 had primary craniosynostosis, others were
  secondary craniosynostosis
• Sagittal 50-58, coronal 20-29, metopic 4-10,
  and lambdoid 2-4.

59
Craniosynostosis

• Raised intracranial pressure is rare with fusion
  of a single suture. It can occur in primary
  craniosynostosis when multiple sutures fuse.
• Signs include sun-setting eyes, papilledema,
  vomiting, and lethargy.
• Craniosynostosis of 1-2 sutures Cosmetic defect
  is the primary morbidity.

60
Diagnosis of Craniosynostosis

• Image studies
• 1. Skull X-ray with AP, lat. and water view
• 2. Cranial CT scan with 3-dimensional
  reconstruction
• Endocrine evaluation Order thyroid and
  parathyroid studies when associated features
  suggest these diagnoses.

61
Treatment of Craniosynostosis

• In patients with microcephaly, investigate the
  cause
• Carefully monitor signs and symptoms of elevated
  intracranial pressure
• Surgery typically is indicated for increased
  intracranial pressure or for cosmetic reasons.

62
Treatment of Craniosynostosis

• Do not operate in patients without IICP until the
  shape of the head does not improve by age 2-4
  months, then the abnormality is unlikely to
  resolve with age
• Cosmetic surgery is performed in infants aged 3-6
  months in the author's practice

63
Cloverleaf skull syndrome
64
Cloverleaf Skull Syndrome

• Kleeblattschädel (ie, cloverleaf skull) results
  from fusion of all sutures except the metopic and
  squamosal sutures, giving the head a cloverleaf
  appearance

65
Cloverleaf Skull Syndrome
66
Cloverleaf Skull Syndrome

• Cloverleaf skull or kleeblattschadel is a rare
  malformation caused by synostosis of multiple
  cranial sutures.
• It can be associated with hydrocephalus,
  proptosis, and hypoplasia of the midface and
  cranial base

67
Cloverleaf Skull Syndrome

• Many syndrome present with cloverleaf skull
  including most of the acrocephalopolysyndactylies
  (Crouzon, Pfeiffer, Carpenter, Apert)
• It is also typical of the type II form of
  thanatophoric dysplasia (another FGFR mutation).

68
Cloverleaf Skull Syndrome

• Differential diagnosis
• 1. Crouzon syndrome
• 2. Apert syndrome
• 3. Pfeiffer syndrome
• 4. Carpenter syndrome
• 5. Thanatophoric dysplasia type II

69
Crouzon Syndrome

• Coronal and sagittal sutures are most commonly
  involved
• Cloverleaf skull is rare and occurs in the most
  severely affected individuals.
• Hydrocephalus (progressive in 30)

70
Crouzon Syndrome
Midface (maxillary) hypoplasia Exophthalmos
secondary to shallow orbits Ocular hypertelorism
Nose Beaked appearance Mouth Mandibular
prognathism Narrow, high, or cleft palate and
bifid uvula
71
Crouzon Syndrome

• Other skeletal features
• Block fusions involving multiple vertebrae,
  Cervical fusion (18), C2-C3 and C5-C6
• Subluxation of the radial heads , Ankylosis of
  the elbows
• Skin
• Approximately 5 of patients have acanthosis
  nigricans, which is detectable after infancy. The
  hallmark of these lesions is a darkened thickened
  skin with accentuated markings and a velvety feel
• Central nervous system
• Approximately 73 of patients have chronic
  tonsillar herniation. Of these, 47 have
  progressive hydrocephalus.
• Syringomyelia may be present.

72
Apert Syndrome

• Coronal sutures most commonly are involved
• Large late-closing fontanels
• Gaping midline defect
• Rare cloverleaf skull anomaly is found in
  approximately 4 of infants

73
Apert Syndrome

• Extremities and digits
• Syndactyly involves the hands and feet with
  partial-to-complete fusion of the digits
• Upper limbs are affected more severely
• Central nervous system
• Intelligence varies from normal to mental
  deficiency
• Papilledema and optic atrophy with loss of vision

74
Apert Syndrome

• Skin
• Hyperhidrosis (common)
• Cardiovascular (10)
• ASD, PDA, VSD, PS, Overriding aorta, CoA,
  Dextrocardia, TOF, Endocardial fibroelastosis
• Genitourinary (9.6)
• Polycystic kidneys, Duplication of renal pelvis,
  etc..
• Gastrointestinal (1.5)
• Pyloric stenosis, Esophageal atresia and
  tracheoesophageal fistula, etc..
• Respiratory (1.5)
• Anomalous tracheal cartilage, Tracheoesophageal
  fistula, Pulmonary aplasia, Absent right middle
  lobe of lung, Absent interlobular lung fissures

75
Pfeiffer Syndrome

• Skull is prematurely fused and unable to grow
  normally
• Bulging wide-set eyes due to shallow eye sockets
  (occular proptosis)
• Underdevelopment of the midface
• Broad, short thumbs and big toes
• Possible webbing of the hands and feet

76
Carpenter's Syndrome

• Head and neck Craniosynostosis first involving
  the sagittal and lambdoid sutures later extending
  to the coronal sutures. Cloverleaf skull may
  occur
• Ears Low set ears and preauricular fistulae.
• Eyes Hypertelorism, mildly downward slanting of
  the palpebral fissures, epicanthic folds,
  microcornea, corneal opacity, and optic atrophy
• Nose Flat nasal bridge.

• Mouth and oral structures A narrow or highly
  arched palate.
• Hand and foot The fingers are short and stubby
  with agenesis of the middle phalanges and soft
  tissue syndactyly, especially of the third and
  fourth fingers.
• Cardiovascular system About one third of all
  cases
• Growth and development Growth retardation is a
  constant feature. Mental retardation is common
  but not constant.

77
Thanatophoric Dysplasia

• Severe growth deficiency with an average length
  of 40 cm at term
• A macrocephalic head with a frontal bossing, a
  flattened nasal bridge, and proptotic eyes
• In TD 2, a cloverleaf-shaped skull resulting from
  premature closure of the cranial sutures
• Narrow thorax with small ribs
• Micromelic limbs with brachydactyly
• Protuberant abdomen
• Hydrocephalus and other cerebral parenchymal
  abnormalities

78
Head Neck Extremities
Crouzon Syndrome
Apert syndrome Coronal sutures most commonly are involved
Pfeiffer syndrome
Carpenter's Syndrome Sagittal and lambdoid sutures later extending to the coronal sutures
Thanatophoric dysplasia type II
79
Craniosynostosis
Crouzon Syndrome
Apert syndrome
Pfeiffer syndrome
Carpenter's Syndrome sagittal and lambdoid sutures later extending to the coronal sutures
Thanatophoric dysplasia type II
80
Cause
Crouzon Syndrome
Apert syndrome
Pfeiffer syndrome
Carpenter's Syndrome
Thanatophoric dysplasia type II
81
Cloverleaf Skull Syndrome

• Genetic anomalies Most are de novo mutation of
  the FGFR1-3.
• ex 1. Crouzon disease?FGFR2
• 2. Thanatophoric dysplasia?FGFR3
• Prognosis When associated with hydrocephalus the
  outcome is usually poor with frequent death in
  infancy
• Surgical management relieving the intracranial
  hypertension and correcting the aesthetic
  appearance.