Craniosynostosis

Question 1

How many parts are there to the skull and what are they called?

Answer 1

1) Neurocranium

2) Viscerocranium

Question 2

What is the Neurocranium?

Answer 2

Neurocranium – forms the protective case around the brain

• The membranous part, which consists of flat bones that surround the brain
• The cartilaginous part which forms bones of the base of the skull.

Question 3

What is the Viscerocranium?

Answer 3

Forms the skeleton of the face

Question 4

How does the skull develop?

Answer 4

• At birth the flat bones of the neurocranium are separated by narrow connective tissue layers known as sutures.
• Where two or more bones meet, the sutures are wide and are termed fontanelles.
• During the birth process, the sutures and fontanelles permit the bones of the skull to overlap and soon after birth the bones return to their original positions
• A large number of the sutures and fontanelles continue to stay membranous for different periods of time after birth, enabling the skull to continue growing.
• The posterior (occipital) fontanelle usually closes around 3 months after birth,
• The anterior (frontal) fontanelle closes around 1 ½ years of age
• The postero-lateral (mastoid) fontanelle closes around 2 years of age.

Question 5

When does the posterior (occipital) fontanelle close?

Answer 5

Usually 3 months after birth

Question 6

When does the anterior (frontal) fontanelle close?

Answer 6

Around 1.5 years old

Question 7

When does the postero-lateral (mastoid) fontanelle close?

Answer 7

Around 2 years of age

Question 8

What is Craniosynostosis?

Answer 8

Premature fusion of 1 or more sutures

• Inhibit growth of skull in that area
• Force growth in other non-fused areas –> abnormally shaped skull

Question 9

What are associated features of Craniosynostosis?

Answer 9

Associated features
- Raised intracranial pressure (ICP)
- Impairment of cerebral function
- Impairment of vision

Question 10

What is the prevalence of craniosynostosis?

Answer 10

1:2000-3000 infants are affected

Question 11

What are the features of Primary Craniosynostosis?

Answer 11

• Sporadic
• Genetically inherited – most commonly autosomal dominant
  (recognised feature in over 100 genetic syndromes)

Question 12

What is Secondary Craniosynostosis?

Answer 12

Acquired Craniosynostosis

• Metabolic disorders e.g hypercalcaemia
• Mechanical cause e.g Intrauterine compression of skull against maternal pelvis

Question 13

What are some types of craniosynostosis?

Answer 13

• Sagittal (Scaphocephaly)
• Metopic (Trignocephaly)
• Unicoronal (Plagiocephaly)
• Bicoronal (Brachycephaly)
• Oxycephaly

Question 14

What is Unicoronal Synostosis?

Answer 14

Plagiocephaly

• Premature fusion of one of the coronal sutures.
• Greater development on the non-fused side and thus asymmetrical growth of the skull.

Question 15

How does the skull look in Unicoronal Synostosis/Plagiophaly?

Answer 15

On the affected side the forehead is relatively flat and the orbit elevated.

On the non-affected side the forehead tends to be excessively prominent.

Question 16

What are some signs/symptoms of unilateral coronal synostosis/plagiocephaly?

Answer 16

Due to the asymmetrical position of the two orbits and the trochleas, it can produce a mechanical weakness of the superior oblique muscles resulting in vertical strabismus, which is frequently associated with inferior oblique over-actions and V-pattern. This can lead to an AHP (chin depression). Other common ocular features include amblyopia (usually strabismic) and astigmatism.

Question 17

What is the treatment in unicoronal synostosis/plagiocephaly?

Answer 17

Fronto-orbital advancement surgery (FOA)

• Performed at 4-12 months of age.
• Aims to correct the existing deformity and minimise the developing facial asymmetry.
• May need further surgery in teenage years
• Long term follow up till skeletal maturity to monitor forehead and facial form.

Question 18

How is Fronto-Orbital Advancement surgery performed?

Answer 18

• Make an incision over the top of child’s head from ear to ear.
• Cut through the coronal sutures to remove the front portion of the upper skull and re-shape it by cutting and trimming the bone to form a more normal shape.
• The bone will be fixed in place using strong stitches that dissolve very gradually over the next few months while the bone heals

Question 19

What is Bicoronal synostosis also known as?

Answer 19

Brachycephaly

Question 20

What is Bicoronal Synostosis (Brachycephaly)?

Answer 20

• Premature fusion of both coronal sutures
• Short anterior-posterior length
• Increased lateral & vertical growth

Question 21

What does Bicoronal Synostosis/Brachycephaly look like in the skull?

Answer 21

• Short antero-posterior skull
• Wide & tall skull
• The face appears flat and broad with very prominent and wide set eyes (hypertelorism).

Question 22

What are some features of Bicoronal Synostosis/Brachycepahly (including ocular features)?

Answer 22

• Brachycephaly is associated with learning disabilities in approximately 50%, together with cleft palate, syndactyly and polydactyly (increased number of fingers & toes). It may also be seen in association with Down’s syndrome.

Ocular Features:
- Proptosis
- Hypertelorism - wide set eyes

Question 23

What is the surgery used in Bicoronal Synostosis/Brachycephaly?

Answer 23

• Fronto-orbital advancement surgery (FOA)
• Performed at 4-12 months of age.

Question 24

What is Saggital Synostosis?

Answer 24

Scaphocephaly

• Premature closure of the sagittal suture
• Prevents lateral expansion of the skull
• Elongation along the anteroposterior axis

Question 25

What is Scaphocephaly also known as?

Answer 25

Sagittal Synostosis

Question 26

What features are present in Sagittal Synostosis/ Scaphocephaly?

Answer 26

- Strong, prominent forehead (frontal bossing of forehead) - Prominent occipital area Associated with - Speech & language delay - Raised intracranial pressure

Question 27

What surgical intervention is involved in Sagittal Synostosis/ Scaphocephaly?

Answer 27

Vault expansion surgery: - Indication: raised ICP and improve appearance (most commonly before 10) - Aim: enlarge space within the skull to allow the growing brain develop and reduce ICP

Question 28

When is vault expansion surgery used?

Answer 28

In Sagittal Synostosis (Scaphocephaly)

Question 29

What is the procedure of vault expansion surgery?

Answer 29

- Procedure: insert metal springs that gradually widen a gap made between the skull bones, which encourage new bone to grow in between the two cut surfaces

Question 30

What is Oxycephaly?

Answer 30

Most severe form of craniosynostosis Premature fusion of coronal, sagittal & lambdoidal sutures As growth is restricted both anteroposterior and lateral, the skull has to grow vertically, developing as a tall and narrow pointed or dome-shaped skull.

Question 31

What are some general signs and symptoms of Oxycephaly?

Answer 31

- Tall & narrow (dome-shaped) skull - High forehead - High, narrow palatal arch - ↑ICP common (increased risk of seizures and brain damage)

Question 32

What are some ocular signs and symptoms of Oxycephaly?

Answer 32

- Optic atrophy - Proptosis (shallow orbits) - Strabismus - Amblyopia - Nystagmus - Hypertelorism

Question 33

What is Metopic Synostosis also known as?

Answer 33

Trigonocephaly

Question 34

What causes metopic synostosis/Trigonocephaly?

Answer 34

This condition occurs as a result of premature closure of the metopic suture causing a prominent central ridge down the forehead and a triangular-shaped skull.

Question 35

What are the general features of metopic synostosis/Trigonocephaly?

Answer 35

- Triangular shaped skull - Prominent central ridge down forehead - Orbits slope down & outwards - The eyes may be closely placed (hypotelorism). - Microcephaly and hypoplasia of the forebrain are frequently observed, and some may also have increased ICP - Learning disability and developmental delay - Astigmatism (usually bilateral) is a common ocular finding, strabismus with associated alphabet-pattern may also be observed.

Question 36

What are the ocular features metopic synostosis/Trigonocephaly?

Answer 36

- Bilateral Astigmatism - Strabismus - Alphabet Pattern

Question 37

What is the most common type of craniosynostosis syndrome?

Answer 37

Crouzon Syndrome

Question 38

What is the most common synostosis in Crouzon Syndrome?

Answer 38

Brachycephaly (bicoronal synostosis) is most frequently observed, but scaphocephaly (sagittal synostosis) and trigonocephaly (metopic synostosis) may also be evidenced.

Question 39

What is the inheritance of Crouzon Syndrome?

Answer 39

- Autosomal dominant - Sporadic - Chromosome 10q25-q26

Question 40

What is the prevalence of Crouzon Syndrome?

Answer 40

- 16.5 per million live birth - 4.8% of all cases of craniosynostosis

Question 41

When does Crouzon Syndrome develop?

Answer 41

During 1st year of life, often first diagnosed 1-2 years of age (as more development = more obvious)

Question 42

What are some general clinical features of Crouzon Syndrome?

Answer 42

- Midfacial hypoplasia; flattened appearance of midface - Orbital shallowing - Hypertelorism (an abnormally increased distance between the bony orbits (eye sockets)) - Downward slanting palpebral fissures - Prominent lower jaw - Hooked nose - Increased ICP - High palatal arch (mouth often half open) - Respiratory difficulties - Deafness - Epilepsy - Learning disability

Question 43

What are some ocular features of Crouzon Syndrome?

Answer 43

- Strabismus (most common feature) V-pattern exotropia - Proptosis spontaneous subluxation of the globe (associated with coughing) - Corneal exposure (due to proptosis) conjunctivitis and keratitis - Amblyopia - Hypermetropia - Optic atrophy - Nystagmus - Cataract - Ectopia lentis - Glaucoma - Iris coloboma - Aniridia (absent iris) - Blue sclera - Micro/ megalocornea - Keratoconus (bilateral)

Question 44

Crouzon Syndrome - If spontaneous subluxation of globe what surgery do we need to do?

Answer 44

- Globe needs to be positioned - Lateral tarsorrhaphy (stitch part of eyelids together) - Craniosynostois sx

Question 45

What causes Apert Syndrome?

Answer 45

Autosomal Dominant but some sporadic cases exist - Both coronal sutures fuse before birth Skull is short from front to back but wide from side to side (Brachycephaly - bicoronal synostosis) Other sutures may also be affected either from birth or later

Question 46

How is skull/facial bones affected in Apert Syndrome?

Answer 46

- Both coronal sutures fuse before birth Skull is short from front to back but wide from side to side (Brachycephaly - bicoronal synostosis) The facial bones are also affected: - Cheekbones and upper jaw do not grow in proportion to the rest of the skull. - The bones around the eyes (orbits) are wider spaced and shallower than usual, causing the eyes to bulge outwards

Question 47

What are some facial features of Apert Syndrome?

Answer 47

As well as the skull and face, the hands and feet are also affected in Apert syndrome with the fingers and toes joined or webbed - Symmetrical syndactyly of fingers and toes (second up to fourth or fifth digit) - Steep forehead - Midfacial hypoplasia - Orbital shallowing - Sloping palpebral fissures - Ear anomalies – ears tend to be low set - Small beaked, humped nose - High palatal arch – mouth is often half open - Cleft palate - Dental anomalies - Prominent lower jaw

Question 48

What are some general features of Apert Syndrome?

Answer 48

- ↑ ICP - hydrocephalus - Respiratory difficulties shortening of the nasopharyngeal space - Congenital heart disease - Learning disability / developmental delay

Question 49

What is the inheritance/prevalence in Apert Syndrome?

Answer 49

Inheritance - Autosomal dominant - Sporadic - Mutation in the FGFR2 gene Prevalence - 1 per 160,000 livebirth - 4.5% of all cases of craniosynostosis

Question 50

What are some ocular features in Apert Syndrome?

Answer 50

- Esotropia or exotropia with V-pattern - Alterations/absence of EOM - Amblyopia - Anisometropia/ astigmatism - Ptosis - Hypertelorism - Mild to moderate proptosis - Corneal abnormalities Keratoconus Corneal scars / ulcers - Optic atrophy - Ectopia lentis - Congenital glaucoma

Question 51

What are some features of Pfeiffer Syndrome?

Answer 51

The facial and ophthalmic features are similar to those seen in Apert’s syndrome, but learning disability is less common and intelligence may in fact be normal. Additional clinical features include acrocephaly, broad thumbs and great toes, and mild syndactyly of the hands. Proptosis is often severe and the majority require medial and lateral tarsorrhaphies. Ocular motility disorders present in approximately 70-75%. Exotropia is slightly more common than esotropia. A- or V-patterns may also be noted. Severe proptosis.

Question 52

What is the inheritance of Pfeiffer Syndrome?

Answer 52

- Autosomal dominant - Mutation in FGFR2 and FGFR1 genes - Can be sporadic

Question 53

What causes Saethre-Chotzen Syndrome & how is it inherited?

Answer 53

Closely related to Crouzon syndrome, Saethre-Chotzen syndrome results from an early closing (fusion) of the skull’s side (coronal) sutures OR back (lambdoidal) suture.  This syndrome is inherited as an autosomal dominant trait with variable expressivity. The gene responsible has been mapped to chromosome 7; mutation in TWIST1 gene

Question 54

What are some features of Saethre-Chotzen Syndrome?

Answer 54

It is characterised by variable skull and facial asymmetry, low set frontal hair-line, flat forehead and short fingers with mild cutaneous syndactyly. The abnormal facial features are often subtle and no proptosis is present. Although ptosis and tear duct abnormalities are commonly present. An esotropia or exotropia with associated V-pattern may be noted. - Facial asymmetry - Low set frontal hairline - Flat forehead - Ears often small, low set - Dental abnormalities 50% - Short fingers with mild syndactyly - Usually normal intelligence

Question 55

What are some ocular features of Saethre-Chotzen Syndrome?

Answer 55

- Ptosis - Strabismus 50% - Nasolacrimal drainage abnormalities with epiphoria 50% Less common (25%) - Optic atrophy - Proptosis

Question 56

What are Clefting Syndrome & some examples?

Answer 56

Disorders of the face - Abnormal development of first and second branchial arch mesoderm in early pregnancy Features of cleft lip and cleft palate - Treacher Collins - Goldenhar’s syndrome

Question 57

What is Treacher Collins Syndrome an example of?

Answer 57

A Clefting Syndrome

Question 58

What is the incidence and inheritance of Treacher Collins Syndrome?

Answer 58

Incidence: approx. 1:50,000 Inheritance - Autosomal dominant - Chromosome 5 q32-33.1 - Mutation in TCOF1 gene

Question 59

What are the abnormalities observed in Treacher Collins Syndrome?

Answer 59

Solely affect the face and associated anatomical structures Bones of the cheek - Bilateral, symmetrical hypoplasia of the zygomatic bone Lower jaw - Hypoplasia of lower jaw → breathing and feeding problems - Receding chin - Abnormal dentition Ears - Small & malformed ears - Middle and inner ear abnormalities - deafness Eyes - Downward slanting palpebral fissures - Colobomas of outer 3rd of lower eyelid - Limbal/orbital dermoids - Nasolacrimal duct obstruction - Astigmatism

Question 60

What is Goldenhar's Syndrome an example of?

Answer 60

A Cleft Palate Syndrome

Question 61

What is the inheritance or Goldenhar's Syndrome?

Answer 61

- Sporadic (inherited sporadic syndrome)

Question 62

Is Goldenhar's Syndrome unilateral or bilateral?

Answer 62

Usually unilateral but can be bilateral and asymmetrical

Question 63

What are some features of Goldenhar's Syndrome?

Answer 63

- Malformations of external & middle ear, maxilla & muscle of mastication (skin tags can be amblyogenic factors) - Facial asymmetry - Cleft palate - Deafness - Dental defects - Vertebral fusion - Cardiac abnormalities - Renal abnormalities - Pulmonary abnormalities

Question 64

What are some ocular features of Goldenhar's Syndrome?

Answer 64

- Orbit on affected side lower & smaller in size - Colobomas of upper eyelid - Dermoid cysts on globe or within orbit - Nasolacrimal duct obstruction - Micropthalmos - Strong association to Duanes syndrome - Esotropia or exotropia - Astigmatism & amblyopia induced by dermoid cyst (pressing on cornea causing astigmatism) - Ptosis

Question 65

What does Goldenhar's Syndrome have a strong association with?

Answer 65

Duane's Syndrome

Question 66

Why do we need to detect ocular abnormalities early?

Answer 66

Important that these disorders are detected early in order to initiate effective management.

Question 67

What must we include in our ophthalmic investigation of craniosynostosis?

Answer 67

- VA - Orthoptic assess - Baseline refraction and fundoscopy - Visual fields if able - OPTOS fundus photography - OCT scans - EDT / VEP

Question 68

What are the general ocular abnormalities in craniosynostosis (Strabimus & OMs)?

Answer 68

Strabismus - Exotropia more common than esotropia - Vertical strabismus OM Abnormal due to: - Abnormal origin of the muscles - Absence of muscles or tendons - Abnormal muscles - MRI scans shown displacement of rectus muscle pulleys (Weiss et al 2014) - V-exotropia pattern (majority) - Upshoot on ad-duction with downshoot of ab-ducting eye Occur as a result of excyclorotated EOM and orbits

Question 69

What are the general ocular abnormalities in craniosynostosis (Refractive Error & Amblyopia)?

Answer 69

Rx: Regular and accurate cycloplegic refractions are essential because refractive error is common and up to 40% may exhibit astigmatism of greater than 1 Dioptre (Khan et al. 2003). Anisometropia may also be identified. However, glasses may need to be custom designed to fit the individual patient with facial anomaly. Amblyopia: Amblyopia is the most common cause of visual impairment in this group of patients! - All types of amblyopia - May be induced by dermoids or ptosis - Initiate occlusion therapy

Question 70

What are the general ocular abnormalities in craniosynostosis (Not Strabismus, OMs, Refractive Error & Amblyopia)?

Answer 70

Optic Neuropathy: with or without papilloedema → by chronically raised ICP or hypoxia → by narrowing of optic canals or stretching of optic nerves Proptosis (exophthalmos): → by orbital shallowing &/or maxillary hypoplasia Exposure keratopathy Photophobia & corneal scarring Incomplete closure of eye lids when asleep Topical lubricants Medial and lateral tarsorrhaphies Electrodiagnostics (VEP’s): ↑ICP not always associated with optic neuropathy VEP’s recommended as abnormal if ↑ICP OCT Scans: Feasible and recommended in clinical surveillance (Rufai et al 2021)

Question 71

What teams are needed to manage craniosynostosis?

Answer 71

The management of patients with craniosynostosis requires a multidisciplinary team approach. Members in the team include paediatrician, plastic surgeon, neurosurgeon, ear-nose-throat (ENT) specialist, paediatric nurses, orthodontist, audiologist, speech therapist, psychologist, geneticist, and genetic counsellor. The ophthalmic team include ophthalmologists, optometrists, orthoptists and visual electrodiagnostic scientists.

Question 72

What is the general management in Craniosynostosis?

Answer 72

Referred to & managed by 4 designated centres in UK - Alder Hey Children's Hospital in Liverpool. - Birmingham Children's Hospital. - Great Ormond Street Hospital in London. - John Radcliffe Hospital in Oxford. At these centres the craniofacial surgery is carried out - Fronto-orbital advancement Aim of surgery - Recreate the sutures & prevent them from reuniting - Enlarges space within skull

Question 73

What is the orthoptists role in craniosynostosis?

Answer 73

Monitor visual development carefully - Sudden visual loss Optic neuropathy - ↑ICP - Amblyopia Occlusion therapy - Good fit of spectacles - Refer for refraction Assess strabismus - Presence/ absence - Change in angle over time – indication if stable Assess OM defects - Any change over time - Associated symptoms

Question 74

What is the ophthalmological management in craniosynostosis?

Answer 74

Ophthalmological management is aimed at ensuring visual development proceeds normally, as facial surgery frequently involves elevations of the orbit and mobilization of the orbital walls. Ophthalmic problems experienced postoperatively may result from trauma to the optic nerve/globe due craniofacial surgery, or due to pressure on the optic nerve/globe by a malpositioned bone graft. It is general practice to delay strabismus surgery until after craniofacial surgery. Orbital imaging is recommended as part of the pre-operative assessment to determine any abnormal or absent extraocular muscles (Nischal, 2002).