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Multiple Sutural Craniosynostosis


KEY POINTS

  • Multiple sutural synostosis can result from a profound degree of prenatal head constraint or genetic mutations in genes associated with a syndromic form of craniosynostosis.

  • Differential diagnosis is important considering the natural history and prognosis of different syndromes.

  • Elevated intracranial pressure is more common in multiple sutural synostosis compared to single suture synostosis.

  • Symptoms include a cloverleaf-shaped head, increased intracranial pressure signs, optic atrophy, proptosis, and loss of vision.

  • Treatment involves early extensive calvarectomy, posterior skull release, fronto-orbital advancement, and possible ventriculoperitoneal shunt insertion.

GENESIS

Constraint as the cause of multiple sutural synostosis (sagittal, metopic, coronal, and/or lambdoid) is unusual and usually results from a profound degree of prenatal head constraint. The complete restoration of normal form after early and effective surgery is much more likely when constraint is the cause of the problem ( Figs. 34.1 and 34.2 ). Multiple sutural synostosis can also result from genetic mutations in one of several genes ( ERF , FGFR1 , FGFR2 , FGFR3 , MEGF8 , MSX2 , POR , RAB23 , RECQL4 , TWIST1 , WDR35 ), all of which result in syndromes that may present with cloverleaf skull. The cloverleaf skull shape is caused by multiple suture synostosis that involves the coronal, lambdoid, and metopic sutures with bulging of the cerebrum through the open sagittal suture or through open squamosal sutures ( Figs. 34.3 and 34.4 ). There may also be synostosis of the sagittal and squamosal sutures with eventration through a widely patent anterior fontanel. One common syndrome associated with cloverleaf skull is thanatophoric dysplasia type 2, which is due to mutations in FGFR3 . Type 2 Pfeiffer syndrome is usually due to mutations in FGFR2 and can result in cloverleaf skull, as can Crouzon syndrome and Apert syndrome, which are also due to mutations in FGFR2 . Some rare syndromes, such as Crouzon syndrome with acanthosis nigricans (see Fig. 34.3B, C ), Baller-Gerold syndrome, and Boston craniosynostosis syndrome, sometimes manifest cloverleaf skull. Baller-Gerold syndrome is a rare autosomal recessive condition with radial aplasia/hypoplasia and craniosynostosis caused by RECQL4 mutations. In Boston craniosynostosis syndrome, the mutant MSX2 product has enhanced affinity for binding to its deoxyribonucleic acid (DNA) target sequence, resulting in activated osteoblastic activity and aggressive cranial ossification. In Crouzon syndrome with acanthosis nigricans (also called Crouzonoid craniosynostosis with acanthosis nigricans), a specific FGFR3 gain-of-function mutation (p.A1a391Glu) leads to early-onset acanthosis nigricans during childhood, often with associated choanal atresia and hydrocephalus. The association of choanal atresia with hydrocephalus in an individual with Crouzon syndrome–like facial features should suggest molecular analysis for this particular mutation, and the combination of hydrocephalus with craniosynostosis may predispose a person toward a cloverleaf skull. It is believed that premature closure of the spheno-occipital synchondrosis is associated with the midface hypoplasia in patients with Crouzon syndrome. Bilateral lambdoid and posterior sagittal synostosis is another rare disorder characterized by invagination of the occipital squame resulting in a step-like deformity of the occiput, and a typical head shape described as anterior turricephaly with mild brachycephaly.

FIGURE 34.1, A , This infant has a cloverleaf skull appearance due to sagittal, coronal, and lambdoidal craniosynostosis. Only the metopic suture was open, and the brain growth ballooned out into this region. The coronal synostosis in addition to the bulging forehead region had distorted the mid- and upper face. A calvarectomy was performed from the supraorbital ridge to below the coronal suture, above the mastoid and the foramen magnum. The aberrant calvarium was discarded, and within several weeks a new calvarium began to form from the remaining dura mater. B , Two months after calvarectomy, the new calvarium had formed functional sutures at the sites of dural reflection and fontanelles, where the sutures join. C , At age 5 years, the patient had not required any additional surgical procedures, and she resembled her older sister in appearance.

FIGURE 34.2, This neonate was born with synostosis of all midline sutures, as well as the superior coronal sutures and medial portions of the lambdoid sutures. He was part of a twin pregnancy in which prenatal ultrasounds showed that he was in a breech position, with his cranium pinched between the legs of his twin brother. The diagnosis of craniosynostosis was suspected prenatally, and the twins were delivered by cesarean section at 29 weeks of gestation. An extensive calvarectomy was performed at age 4 months. The patient is 3 months old in the preoperative photographs ( A ) and 12 months old in photographs taken after cranial orthotic therapy ( C ). His postoperative cephalic index of 103% was reduced to 92% after 5 months of orthotic therapy. B , Note prominent convolutional markings over the superior portions of the skull in the three-dimensional computed tomography scans. Such findings suggest increased intracranial pressure.

FIGURE 34.3, A , This patient has Crouzonoid craniosynostosis with acanthosis nigricans due to an Ala391Glu substitution in FGFR3 , resulting in multiple suture synostosis and a cloverleaf skull at age 9 days. He had associated hydrocephalus and choanal atresia, and required early posterior and anterior cranial reconstruction in addition to shunting for hydrocephalus and tracheostomy for choanal atresia.FIGURE 34.3, cont'd B , The same patient after posterior remodeling and shunting for hydrocephalus at age 9 days and anterior remodeling at age 9 months. C , From ages 2 to 24 months, the patient received cranial orthotic therapy after both surgical procedures to channel brain growth into a symmetric cranial shape. By the end of this treatment period, striking acanthosis nigricans was apparent, leading to the diagnosis of Crouzonoid craniosynostosis with acanthosis nigricans due to an Ala391Glu substitution in FGFR3 . The use of two consecutive postoperative orthotics facilitated optimal correction after each subtotal calvarectomy and prevented excessive molding after each surgery.

FIGURE 34.4, A , This patient also has multiple suture synostosis resulting in a cloverleaf skull (top) , but no mutation could be found in FGFR1 , FGFR2 , FGFR3 , TWIST , MSX2 , or ALX4 . B , Three-dimensional computed tomography scans show multiple sutural synostosis with multiple areas of cranial thinning.

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