The term craniosynostosis refers to the process of premature bony fusion of the cranial sutures. The term is frequently used interchangeably with the word craniostenosis, which technically refers to the aberrant skull shape that results from the process of craniosynostosis (Graham, 1981). The weight of the brain doubles during the first year of life, and enlargement of the skull vault is distributed among the main cranial sutures—sagittal, coronal, lambdoid, and metopic. Premature fusion of a suture leads to reduced growth in the direction perpendicular to the fused suture (Thompson et al., 1994). Compensatory growth occurs in the remaining normal sutures. Normally, the cranial sutures are open at birth and become interdigitated by 7.5 months of age. Cranial sutures do not fuse completely until the fourth decade of life (Graham, 1981).

It is important to determine whether craniosynostosis is primary or secondary. In primary craniosynostosis, abnormal skull development is genetically determined and alteration in sutural growth is present from birth (Flores-Sarnat, 2002). In primary craniosynostosis, the head of the affected individual is frequently asymmetric. The brain grows at a normal rate but must adjust to the confined space. The brain continues to grow in areas where the sutures are open but not in areas where the sutures are closed (Lyons-Jones et al., 1980). Most children affected with primary craniosynostosis are normal neurologically and benefit from surgery. In secondary craniosynostosis, brain growth is impaired and most affected children are neurologically abnormal. In secondary craniosynostosis, a metabolic, storage, hematologic, or structural disorder results in microcephaly or otherwise abnormal brain growth (Table 10-1). In evaluating the fetus with craniosynostosis, it is important to determine whether the craniosynostosis is isolated (80–90% of cases) or syndromic (10–20% of cases). More than 150 syndromes have been described that include craniosynostosis as an associated feature (Lajeunie et al., 1995; Warren and Longaker, 2001).

Isolated craniosynostosis generally presents during the first year of life, and severe neuropsychologic sequelae are unusual (Meilstrup et al., 1995). In most studies, the sagittal suture is the most common site for isolated craniosynostosis (Figure 10-1). This is called “scaphocephaly,” and it results in a narrow, elongated head. Physical examination reveals a palpable ridge along the line of the fused suture. Bilateral coronal craniosynostosis (Figure 10-2) leads to “acrobrachycephaly” and a broad, short head (Flores-Sarnat, 2002). Unilateral coronal craniosynostosis, called “plagiocephaly,” results in asymmetric flattening of the forehead with loss of the supraorbital ridge. This condition is best appreciated when viewed from above the patient. In most reported studies, the least commonly involved suture is the metopic. This is called “trigonocephaly,” and produces a keel-shaped forehead and orbital hypotelorism (Thompson et al., 1994). The kleeblattschädel deformity, also described as a cloverleaf skull, has a more symmetric trilobar appearance, which results from premature synostosis of the coronal and lambdoidal sutures (Meilstrup et al., 1995).

Craniosynostosis is one of the most common human malformations, with an incidence of approximately 1 in 2000 livebirths (Shuper et al., 1985; Lajeunie et al., 1995; Van der Ham et al., 1995). Craniosynostosis is associated with advanced paternal age (Lajeunie et al., 1995), maternal smoking, and higher altitudes (Alderman et al., 1994, 1995). In a study of 154 patients at Johns Hopkins Hospital followed over a 2-year period, Van der Kolk and Beatty (1994) found that 78% of affected patients had only one suture involved, whereas 16% of patients had multiple sutures involved. Of these 154 patients, 94% had isolated craniosynostosis and 6% had complex or syndromic craniosynostosis. In this study, secondary synostosis occurred in four patients as a result of microcephaly or following complications of ventriculoperitoneal shunt placement (Van der Kolk and Beatty, 1994). Craniosynostosis occurs in all ethnic and racial groups.

Of the syndromic craniosynostoses, the most common are Saethre–Chotzen syndrome (Lewanda et al., 1994) and Muenke coronal craniosynostosis (Muenke et al., 1997). The next most common is Crouzon syndrome, with an incidence of 1 per 25,000 livebirths (Leo et al., 1991). Apert syndrome, with its distinctive craniofacial and digital abnormalities, occurs in 1 per 65,000 to 160,000 livebirths (Chenowith-Mitchell and Cohen, 1994; Moloney et al., 1996). Apert syndrome is associated with advanced paternal age (Moloney et al., 1996).

Prenatal sonographic evaluation of the fetus in which craniosynostosis is suspected should include examination of

1. 
   

   the symmetry of the calvarium contour (coronal views through temporal lobes and orbits);

   
   
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   the continuity of the calvarium to exclude encephalocele;

   
   
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   the size and shape of the orbits;

   
   
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   the cerebral ventricles;

   
   
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   the brain parenchyma;

   
   
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   the overall head size;

   
   
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   the remainder of fetal anatomy by detailed sonography (Meilstrup et al., 1995).

The most important consideration in the sonographic examination is the distinction between isolated and syndromic craniosynostosis. For most of the conditions associated with craniosynostosis, long-bone growth is within normal limits. It is particularly important to evaluate the fetal hands and feet, the central nervous system, and the heart.

In most published reports of prenatal diagnosis of craniosynostosis, the diagnosis was not made until the third trimester, unless a family history was present for one of the associated syndromes. In one report, 16 fetuses at risk for craniosynostosis were referred to a fetal medicine unit because of a positive family history (Delahaye et al., 2003). Serial sonographic examinations were performed at 12, 22, and 32 weeks of gestation. In all cases, postnatal diagnosis agreed with the third trimester (and, in a few cases, second trimester) diagnosis. Craniosynostosis was diagnosed when there was a loss of hypoechogenicity of the normal suture. Sutures were examined along their entire length. Dysmorphology and skull deformity preceded closure of the sutures by 4 to 16 weeks.

Fetuses at risk for Apert syndrome (Figure 10-3) should be evaluated for abnormalities of the hands (syndactyly), proptosis, congenital heart defects, agenesis of the corpus callosum, and abnormalities of the limbic structures of the brain (de León et al., 1987; Skidmore et al., 2003; Hansen et al., 2004). At least one case has been reported of Apert syndrome presenting as fetal hydrocephalus, although the presence of hydrocephalus is considered controversial (Kim et al., 1986). Some authors prefer to use the term distortion ventriculomegaly to indicate that the apparent abnormalities in fluid are the result of the misshapen brain (Cohen and Kreiborg, 1993b). One case of Apert syndrome presenting as nuchal-fold thickening as early as 12 weeks of gestation has been described (Chenowith-Mitchell and Cohen, 1994). This fetus did not demonstrate any additional sonographic abnormalities until after 26 weeks of gestation, when an abnormal head shape was first noted. By 29 weeks of gestation, the fetal skull was demonstrated to have prominent parietal lobes, and for the first time, lack of separate fetal finger movement was noted. This latter finding of the absence of distinct and separate movements of the fingers and toes is considered to be one of the hallmarks of Apert syndrome (Hill et al., 1987). Three-dimensional (3-D) sonographic imaging has been shown to be useful in the diagnosis of a sporadic case of Apert syndrome, specifically by demonstrating a widely open metopic suture and bilateral fusion of the coronal sutures (Esser et al., 2005).

Pfeiffer syndrome is characterized by coronal craniosynostosis, midface hypoplasia, and broad thumbs and great toes. There are three clinical subtypes: type I is the mildest presentation, type II is the most severe, and type III is intermediate. Type II is associated with a cloverleaf-shaped skull, severe ocular proptosis, midface hypoplasia, radially deviated digits, and occasional ventriculomegaly (Benacerraf et al., 2000). Several cases of the sonographic diagnosis of Pfeiffer syndrome, type II, with molecular confirmation, have been reported in the literature (Benacerraf et al., 2000; Blaumeiser et al., 2004; Gorincour et al., 2005).

Whenever craniosynostosis is considered in a fetus, an attempt should be made to rule out encephalocele (see Chapter 12) and the presence of an intracranial mass. Craniosynostosis is associated with abnormalities of chromosomes 5p, 7p, and 13q, single-gene disorders, and rare teratogens, such as aminopterin.

The most common conditions associated with syndromic craniosynostosis include Saethre–Chotzen syndrome, which includes craniosynostosis, facial asymmetry, low frontal hairline, ptosis, a deviated nasal septum, brachydactyly, and partial cutaneous syndactyly of the toes (Lewanda et al., 1994). Saethre–Chotzen syndrome is dominantly inherited, but in some families the features are so mild that they may go unrecognized.

A relatively recently identified syndrome, Muenke coronal craniosynostosis, has significant clinical overlap with Saethre–Chotzen syndrome (Vajo et al., 2000). It is also quite common. There is considerable phenotypic variability in this condition and mild cases may be missed. Affected individuals have coronal craniosynostosis, and mild abnormalities of the hands and feet, including carpal and tarsal fusion, brachydactyly, thimble-like middle phalanges, and cone-shaped epiphyses. Additional findings include sensorineural hearing loss and developmental delay (Muenke et al., 1997). This condition is also dominantly inherited.

The next most common syndrome associated with craniosynostosis is Crouzon syndrome, which includes coronal craniosynostosis, maxillary hypoplasia, shallow orbits, and ocular proptosis. This condition was first described in 1912 in an affected mother and daughter (Leo et al., 1991). Crouzon syndrome is distinguished from some of the other syndromes by the absence of abnormalities in the hands and feet. The essential features of this syndrome are limited to the skull and face, resulting in brachycephaly and orbital hypoplasia (Thompson et al., 1994).

Less common syndromes in the differential diagnosis include Jackson–Weiss, Pfeiffer (types I, II, III) and Carpenter. Jackson–Weiss syndrome was first described in an Amish kindred with more than 130 affected family members. The characteristic findings of Jackson–Weiss syndrome include craniosynostosis, maxillary retrusion, frontal prominence, hypotelorism, strabismus, and in general, anomalies of the feet but not the hands. The characteristic anomalies of the feet include medial deviation of the big toes and partial syndactyly of the first web space (Stankovic et al., 1994). Pfeiffer syndrome has three forms. There is a relatively benign form, known as the type I, which consists of an acrocephalic skull due to bicoronal synostoses. Affected patients have broad thumbs and great toes and soft tissue syndactyly. Like many of the other syndromes associated with craniosynostosis, affected patients have hypotelorism, maxillary hypoplasia, low-set ears, and normal intelligence (Hill and Grzybeck, 1994). Two other subgroups of patients with Pfeiffer syndrome had extreme proctosis and hydrocephalus. These patients have a uniformly poor outcome and are distinguished from each other as the type II form with the cloverleaf skull deformity and the type III form without the cloverleaf skull deformity (Moore et al., 1995). The kleeblattschädel, or cloverleaf, skull deformity is also associated with thanatophoric dysplasia (see Chapter 90). Of all patients with the cloverleaf skull deformity, 20% are due to Pfeiffer syndrome and 40% are due to thanatophoric dysplasia (Hill and Grzybeck, 1994). In Carpenter syndrome, affected patients have acrocephaly, soft-tissue syndactyly, radial/tibial polydactyly, congenital heart disease, and mental retardation. In Baller– Gerold syndrome, affected patients have craniosynostosis and radial/tibial upper-limb malformations (see Chapter 106) (Boudreaux et al., 1990).