► [Persistent patency of cranial sutures and fontanels at a time when they are meant to be closed]
The sutures and fontanels are prominent in the newborn, diminishing in size as ossification of the skull proceeds throughout childhood and early adulthood. The anterior fontanel is wide open at birth and shrinks to fingertip size by the age of 15-18 months. The posterior fontanel is usually closed to palpation by 4 months of life, but occasionally closure is evident at birth. The cranial sutures are normally patent in infants and children and are visible on radiograms as radiolucent lines that undergo progressive narrowing and sclerosis until complete fusion is attained at the end of adolescence. In children under 2-3 years of age the sutures can be prominent, and even in normal neonates they can be 1 cm or more wide (Tan 1976). Maintenance of open sutural spaces is guaranteed by a process of active resorption (Manzanares et al. 1988). Incidentally, normal patency of sutures and fontanels contributes significantly to the uniquely elastic properties of the pediatric skull (Margulies and Thibault 2000). The mendosal (occipital) synchondrosis usually fuses during the 1st week of life, while the metopic (frontal) suture usually closes at about 2 years. The spheno-occipital synchondroses are no longer patent at the age of 20-25 years, while the coronal, sagittal, and lambdoid sutures are obliterated at approximately 30 years of age. In adulthood, together with sutural closure, parasutural sclerosis also develops (Furuya et al. 1984). However, there is considerable variability in the timing of suture closure - a limitation to the use of suture appearance as a reliable indicator of the developmental age of the skull (Silverman et al. 1993). Wide cranial fontanels and sutures (especially coronal suture) occur as a normal finding in premature infants and in children who are experiencing brain rebound growth after a period of growth suppression, as seen during recovery from chronic diseases or deprivational dwarfism (Swischuk 1974; Capitanio and Kirkpatrick 1969).
As discussed elsewhere in this chapter, a number of signaling molecules and transcription factors are involved in the regulation of sutural morphogenesis. Mutations leading to functional haploinsufficiency of the TWIST gene and gain-of-function mutations in the MSX2 and FGFRs genes cause craniosynostosis syndromes (Jabs 1998), whereas loss-of-function mutations in the MSX2, ALX4, and CBFA1 genes are involved, respectively, in the development of parietal foramina, cranium bifidum, and persistently open fontanels of cleidocranial dysplasia (Mundlos et al. 1997; Wilkie et al. 2000; Wuyts et al. 2000). In addi-tion,trisomy 7p21 involving the TWIST locus has been associated with unusually large,late-closing fontanels, suggesting that TWIST may lie in a dosage-sensitive pathway controlling the differentiation of the sutural mesenchymal cells (Stankiewicz et al. 2001).
There are several possible mechanisms underlying delayed closure or incomplete ossification of sutures and fontanels, including a primary defect in bone ossification, increased intracranial pressure, and direct infiltration of sutures by pathologic tissue.
Disorders Associated with Deficient Ossification of the Skull. Failure of the fontanels and sutures to close is quite a common calvarial defect shared by some 250 syndromes. The prototypical disorder is cleidocranial dysplasia (OMIM 119600), which is characterized by wide, late-closing fontanels and sutures, multiple wormian bones, and a large brachycephalic head with prominent frontal and parietal bones, the so-called Arnold head. Involvement of the skull base and facial bones is less extensive, resulting in small sphenoid bones, posterior notching of the foramen magnum, platybasia, midfacial hypoplasia, and late or incomplete development of paranasal sinuses and mastoid air cells. Ossification of the maxilla and the mandible is grossly normal (Jensen and Kreiborg 1993), whereas dentition is markedly affected, with late eruption of both deciduous and permanent teeth, variation in the number of teeth, malformed roots, enamel hypoplasia, and retention cysts (Jarvis and Keats 1974). Delayed closure and/or widening of the cranial sutures and fontanels, multiple wormian bones, and poorly mineralized, soft calvarium (caput membranaceum) are typical manifestations of osteogenesis imperfecta, type IIA (OMIM 166210). In the autosomal dominant form of osteogenesis imperfecta (Lobstein disease, OMIM 166200) there are multiple wormian bones, macrocephaly with a triangular face, and either normal or osteoporotic bone skull density. A poorly ossified, large cranium with widely patent fontanels and sutures is seen in achondrogen esis type IA and IB (OMIM 200600,600972) and type II (OMIM 200610), and also in fibrochondrogenesis (OMIM 228520). Skull ossification is severely impaired or totally absent in hypophosphatasia (OMIM 241500), whereas in thanatophoric dysplasia (OMIM 187600) a large cranium with wide anterior fontanel and full forehead is associated with short skull base and foramen magnum. Delayed membranous cranial ossification (OMIM 155980) has been described in two separate families in the absence of other skeletal abnormalities (Gonzalez-del Angel et al. 1992; Cargile et al. 2000). In the first family, an 11-month-old girl had a large ossification defect involving the parietal bones, the squamous portion of the temporal bones, and the interparietal region of the occipital bone, while her mother had a completely ossified cranial vault with more evident sagittal and lambdoid sutures than would normally be expected in a 31-year-old individual. Both had similar faces, with frontal bossing, hypertelorism, downward slanting palpe-bral fissures, flat nasal bridge, and short midface. The mother had had a soft skull vault during infancy, which had become progressively harder with no treatment (Gonzalez-del Angel et al. 1992). In the second family, delayed membranous cranial ossification was segregating with an apparently balanced reciprocal translocation between chromosomes 2 and 3 over three generations (Cargile et al. 2000). A previously unrecognized association of wide open calvar-ial sutures with large and late-closing anterior fontanel, congenital cataract, craniofacial anomalies (frontal bossing, hypertelorism, relative maxillary hypoplasia, capillary hemangioma of forehead, broad and prominent nose), and skeletal defects (joint hypermobility, flat feet, scoliosis) has been identified in an inbred Saudi Arabian family (Boyad-jiev et al. 2003) (Fig. 1.20a-d). Given the consanguineous relationships within this pedigree, autosomal recessive inheritance has been suggested. Linkage to chromosome 14q13-q21 was demonstrated. Despite some similarities, such disorders as frontonasal dysplasia, Hallermann-Streiff syndrome, and cleidocranial dysplasia were excluded. In particular, normal clavicular ossification, absence of multiple wormian bones, presence of cataract and typical skin changes, and the inheritance pattern ruled out clei-docranial dysplasia. Osseous changes of rickets are usually recognized after several months of vitamin D deficiency (babies born to mothers with long-standing osteomalacia may be symptomatic at birth) (Park et al. 1987). One of the early signs, craniotabes, consists in a 'ping-pong ball' sensation obtained when firm pressure is applied over the occiput or posterior
Fig. 1.20 a-d. Cranio-lenticulo-sutural dysplasia in two affected children (a, b a boy; c, d a girl) in the same sibship. Note the major features of this hitherto unreported dysmor-phic syndrome: wide nonossified anterior fontanels extending
Fig. 1.20 a-d. Cranio-lenticulo-sutural dysplasia in two affected children (a, b a boy; c, d a girl) in the same sibship. Note the major features of this hitherto unreported dysmor-phic syndrome: wide nonossified anterior fontanels extending into the frontal region, open sutures, hyperpigmented skin over the fontanels, frontal bossing, hypertelorism, a broad nasal bridge, and relative maxillary hypoplasia. (From Boyadjiev et al. 2003)
parietal bones, owing to thinning of the outer table of the skull. The anterior fontanel is larger than normal: its closure may be delayed until after the 2nd year of life. Roentgenograms usually reveal thickening of the central portion of the parietal and frontal bones, which results in prominences that give a box-like appearance (caput quadratum). The head may be larger than normal. Eruption of deciduous teeth may be delayed, and there may be defects of the enamel and extensive caries (Barness 1987). In children with untreated hypothyroidism, delayed closure of fontanels and sutures and multiple wormian bones represent the cranial counterpart of the generalized defect of skeletal ossification,which manifests with prominent abnormalities at the level of the ossifying epiphyses (epiphyseal dysgenesis). Skull underossification can occur in disorders with prenatal-onset growth retardation, notably rubella infection. Persistent patency of the anterior fontanel, wormian bones, and diffuse osteosclerosis are characteristic features of pykno-dysostosis (OMIM 265800). Another sclerosing disorder, Lenz-Majewski syndrome (OMIM 151050), is characterized by a disproportionately large head with wide fontanels and separated, late-closing sutures, in addition to progressive sclerosis of the skull, facial bones, and vertebrae (Gorlin and Whitley 1983). Further radiographic manifestations include broad clavicles and ribs; short or absent middle phalanges; diaphyseal undermodeling and midshaft cortical thickening; metaphyseal and epiphyseal hypostosis; retarded skeletal maturation; and defective tooth enamel. Unlike craniometaphyseal and craniodiaphyseal dysplasias, the conditions most likely to be mistaken for this disorder, Lenz-Majews-ki syndrome does not appear to involve any impingement on cranial nerves. Distinguishing features include loose, atro-phic skin with prominent veins on the scalp, large floppy ears, choanal atresia or stenosis, nasolacrimal duct obstruction, cryptorchidism and inguinal hernia in boys, failure to thrive, and mental retardation.
Increased Intracranial Pressure. The importance of such clinical signs as increased rate of head growth and ocular disturbances has been emphasized earlier in this chapter in the section headed "Macrocephaly". Widening of the cranial sutures and bulging of fontanels are major radiographic manifestations of cranial hypertension during the first few months of life. Additional features, which are especially prominent in cases with long-standing symptoms, include progressive calvarial thinning, frontal bossing, craniofacial disproportion and, occasional ly, a 'hammered silver' appearance of the calvarium. However, the current availability of more sensitive pediatric brain imaging modalities, such as ultrasound, CT, and MR, has confined conventional radiography to a marginal role in the diagnosis of cranial hypertension and underlying disorders. The degree and pace of sutural spreading are inversely related to patient age. Thus, in young infants sutural spreading may occur as early as in the first 24-48 hours after the onset of cranial hypertension (Holmes et al. 1977), whereas in older children it may take several weeks for the same degree of sutural spreading to occur. Usually the coronal suture enlarges first, followed by the sagittal, lambdoid, and squamosal sutures. In neonates, a rapid increase in intracranial pressure is often associated with spreading of all the sutures. Widening of the anterior fontanel occurs early, usually in combination with a variable degree of bulging.
Direct Infiltration of Sutures and Fontanels. An osteode-structive pattern at the sutural edges, with indistinct sutural margins and nonuniform sutural spreading, may be seen in some pediatric patients with neoplasms, most notably metastatic neuroblastoma. Involvement of the external surface of the dura, with separation of the brain parenchyma from the bony calvarium, is common in this disease. The dural metastases are continuous with subcutaneous deposits via the separated sutures (Chirathival and Post 1980). Increased intracranial pressure caused by infiltration of meninges in combination with bone destruction at the sutural margins may lead to sutural diastasis in children with leukemia (Azzarelli and Roessmann 1977).
Was this article helpful?
Have you recently experienced hearing loss? Most probably you need hearing aids, but don't know much about them. To learn everything you need to know about hearing aids, read the eBook, Hearing Aids Inside Out. The book comprises 113 pages of excellent content utterly free of technical jargon, written in simple language, and in a flowing style that can easily be read and understood by all.