Craniosynostosis

Etiology

Craniosynostosis can classify as simple when involving a single suture and complex when involving multiple sutures. Another popular way to classify them is in syndromic (Apert, Crouzon, Pfeiffer) and non-syndromic with an isolated finding. [1][3]

Epidemiology

The prevalence of craniosynostosis is 1 per 2000 to 1 per 2500 live births. It has risen with time, the predisposing factors being either environmental (maternal smoking, in utero exposure to teratogens, intrauterine constraint, fetal positioning) or genetic (mutations). Almost 20% of all craniosynostoses are due to genetic causes, most of these being inherited in an autosomal dominant fashion, although new mutations arise in 50% of cases.[2] Non-syndromic craniosynostosis occurs in 75% of cases, and 25% account for syndromic craniosynostosis.[2]

The craniosynostoses are classified depending on the suture that is affected, sagittal being affected in 55% to 60% of the cases, coronal (20% to 25%), metopic (approximately15%) and lambdoid (3% to 5%). Clinical identification is usually within the first year of life.[1][2]

History and Physical

As with any other condition, a thorough history and physical examination are most helpful in determining the diagnosis.

While taking the history, it is vital to know if there is any family history of abnormal head shapes, in utero exposure to teratogenic drugs, intrauterine restrains, or an abnormal fetal position, as well as any complications during pregnancy and any delayed milestones.

The physical examination allows the clinician to evaluate whether a suture fusion is present and whether any concomitant features would make the craniosynostosis part of a syndrome, like any congenital anomalies and dysmorphic features.

Assessing the skull is critical. Looking at it from all directions and measuring the head circumference to calculate the cephalic index (maximum breadth of the skull multiplied by 100 divided by the maximum length of the skull). The examiner should also note and touch the scalp to feel any sutural ridging, prominent vessels over the skull, and examine and measure the fontanelles.[2]

Besides these, depending on the severity of the condition, the patient might present with other clinical manifestations as consequences of the craniosynostosis, which must be kept in mind and monitored. Therefore an ophthalmologic examination should be done if any signs of intracranial pressure (ICP) are present which will show papilledema. Examine possible airway obstructions and feeding difficulties.

The different non-syndromic craniosynostoses are described below:

• Scaphocephaly or dolichocephaly (premature fusion of the sagittal suture). These patients have a long, narrow-shaped head with a higher anteroposterior diameter. Frontal bossing is often present.[2][1][4]
• Anterior plagiocephaly (premature fusion of 1 coronal suture). The forehead appears flat on the affected side, Harlequin sign (high supraorbital margins seen in radiographs), frontal bossing on the unaffected side, and nasal deviation towards the normal side.[2][1]
• Posterior plagiocephaly (premature fusion of 1 lambdoid suture). Frontal and occipital bossing, ipsilateral ear moved downward, from above the head looks like a trapeze.[2][1][4]
• Trigonocephaly (premature fusion of the metopic suture). The forehead is narrow and pointed; the head has a triangular shape viewed from above, hypotelorism.[2][1]
• Brachycephaly (bi-coronal premature fusion). Short skull, forehead, and occiput flattened but the frontal bone in long (vertically) and prominent, hypertelorism, and Harlequin malformation.[2][1][4]
• Oxycephaly (turricephaly). The fusion of all or most of the cranial sutures.

The different syndrome presenting with craniosynostoses are described below:

• Apert: affects coronal suture. Presenting with midface hypoplasia, hypertelorism (bulging and wide-set eyes), beaked nose, underdeveloped jaw (that leads to crowded teeth), syndactyly of hands and feet, hearing loss. They can have mild to moderate intellectual disabilities.[4][5][6][7]
• Crouzon: affects coronal, sagittal, and/or lambdoid sutures; features midface hypoplasia, beaked nose, exophthalmos, hypertelorism, cervical vertebral fusion, and hearing loss. Some can present with cleft lip and/or palate. They usually have normal intelligence.[4][5][6][7]
• Pfeiffer: features brachycephaly (bi-coronal sutures), hypertelorism, maxillary hypoplasia, broad thumbs, great toe, syndactyly, brachydactyly, hearing loss.[4][7]
• Muenke: affecting coronal suture (uni or bilateral); features midface hypoplasia, hypertelorism, macrocephaly, and hearing loss.[4][6][7]
• Kleeblattschadel (cloverleaf deformity, synostosis of the coronal and lambdoid sutures producing a tri-lobar-shaped head): featuring “beak-shaped” nose, maxillary hypoplasia with proptosis, ears displaced inferiorly. This craniosynostosis is associated with hydrocephalus.[8]

Evaluation

Although the diagnosis is clinical, many professionals will require radiologic imaging to evaluate further and confirm the diagnosis.

The most accurate method is the CT scan with 3D reconstruction, where all sutures are assessable, but due to the radiation risk, this option requires thoughtful consideration. Plain x-rays are low-cost. Therefore they are useful to assess infants will low risk of craniosynostosis, but it is not accurate enough. MRI is less accurate when compared to CT, but is still a great method to use, but usually reserved for children in which the CT revealed any anomalies of the brain.[2] 

Ultrasound is a low-cost modality (but technician-dependent) that can only be used with open fontanelles but is very useful to visualize and follow up the sutures at every examination.

New modalities are now in use, like GRASE (gradient-and-spin-echo), a type of MRI, which enhances bone-soft tissue boundaries showing the cranial sutures as hyperintense.[2]

When encountered with syndromic craniosynostosis, genetic testing is the usual followup (recommended mostly when two or more sutures are affected), testing for FGF receptor genes, which have been the genes most commonly related to these syndromes. FGFR2 and FGFR3 undergo testing, as well as transcription factors (TWIST, MSX2). Increasing levels of research have taken place to understand and determine the genetic causes of these syndromes. To date, 57 genes have been identified to have a relationship and be the underlying cause of the craniosynostosis, the most common ones being the ones mentioned above.[2][3][6]

Treatment / Management

The management of these patients depends on the kind of craniosynostosis. The uncomplicated and non-syndromic types can be managed surgically but electively compared to some syndromic forms that require urgent surgical intervention due to the involvement of the airway, ophthalmologic, and neurological system.[1][2] A conservative approach with remodeling helmets could be attempted first in cases in which unilateral craniosynostosis is not too severe.[2]

The extent, as well as the type of surgery, depends on the age and presentation of the patient. Two modalities are in use:

• Endoscopic suturectomy: done in a patient less than six months of age because the bone is more flexible and manageable by an endoscope. The postoperative recovery is faster, there is less blood loss, and the surgery is shorter compared to open craniotomy. The only downside is that most times, there is a need to combine the surgery with the postoperative use of remodeling helmet for 4 to 6 months.[1][2]
• Open craniotomy: done in patients older than six months because the bones are more rigid and cannot be manipulated as well with an endoscope. This modality allows for a better remodeling of the skull and decreases the need for helmet use postoperatively.[1][2]

The main goal of surgery is to create enough space in the cranial vault for the brain to grow and develop properly as well as to provide the child with a more decent-looking appearance.

The best time in which the correction should be done is between 6 to 12 months of age when there are no signs of increased ICP or airway compromise, and this correlates with the period in which the infant’s brain and head grow the most.[2]

The need for additional intervention can always arise and is more bound to occur in syndromic cases.[1]

Differential Diagnosis

Positional plagiocephaly requires differentiation from craniosynostosis. It has no premature fusion of sutures. It presents with a parallelogram of the head, ipsilateral anterior displacement of the ear and head, ipsilateral occipital flattening with contralateral occipital bossing.[5][6] The prevalence has increased over time due to the "back to sleep campaign" to reduce the incidence of sudden infant death syndrome. Still, the only concern is cosmetic, and it can be managed supportively by alternating the side of the head on which the baby sleeps. Remodeling helmets are also an option. This condition does not require surgical intervention and does not affect neurologic development. Parents should be reassured and instructed to continue making the baby sleep on his back.[2][9][1]

Prognosis

Left untreated, craniosynostosis can affect the development of the child; this is due to the restriction for growth of the brain and damage to the brain tissue due to increased intracranial pressure.[5][6] The degree of developmental delay hinges on the kind of craniosynostosis. Children with sagittal synostosis have a lower risk of learning disabilities compared to those with metopic, uni-coronal, or lambdoid synostosis. With early identification of developmental gaps and placement in support programs, a negative academic and cognitive outcome for these children could be reduced if not prevented.[2][10]

When surgical intervention occurs promptly, cases have an excellent outcome with relatively normal growth and development. Follow up for another fusion of sutures and head growth is crucial to determine the need for re-intervention in these patients, with a particular focus on syndromic craniosynostosis. [2][1]

Complications

Surgical treatment can lead to several complications like postoperative hyperthermia (most common), infections (meningitis), seizures, subgaleal hematoma, subcutaneous hematoma, and cerebrospinal fluid leakage. The risk of complications increases with reintervention, as well as with open craniotomy (compared to the endoscopic approach where the complications are minimal). In case of severe blood loss, mortality and morbidity can reach up to 50%.[2]