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As innate as admiring a new baby and congratulating the parents when we enter the room, our tendency as pediatricians to palpate the anterior fontanel when we meet an infant, the “pediatrician’s handshake,” is universal. Why do we do this?
As innate as admiring a new baby and congratulating the parents when we enter the room, our tendency as pediatricians to palpate the anterior fontanel when we meet an infant, the “pediatrician’s handshake,” is universal. Why do we do this? Does it allow for a more intimate connection with our patient who cannot yet return a greeting? Does it reassure us to feel a subtle pulsation? Perhaps feeling its size helps convince us that the brain is growing well, or maybe we appreciate the fontanel because this unique window to the brain will not persist for long.
The information we gain from examining the fontanel is extensive. This article reviews the development of the fontanel, its clinical significance, the wide range of normal presentation, and discusses abnormalities of the fontanel and what this can teach us about our patients.
The newborn calvaria is normally comprised of 7 bones: the paired frontal, temporal, and parietal bones, and the single occipital bone. As these bones grow radially from membranous ossification centers, sutures form at the junctions of the calvaria and fontanels form at the intersection of sutures.
IMAGE CREDIT: PAUL JOSEPH BROWN / GAPPSSix fontanels are in the newborn skull, including the anterior and posterior fontanels and the paired mastoid and sphenoid fontanels (Figure 1). The triangular posterior fontanel is found at the junction of the sagittal and lambdoid sutures, and normally closes by 8 weeks.1 Although the fontanel does not truly close until the second decade of life, for purposes of this discussion it is closed when a fontanel is too small to be identified on physical exam. The diamond-shaped anterior fontanel forms at the junction of the coronal, metopic, and sagittal sutures. In addition, the mastoid fontanel (the asterion or star) forms at the posterior end of the parietomastoid suture, at the junction of the squamosal suture, mendosal suture, and extraoccipital synchondroses. The sphenoid fontanel (pterion) forms from the juncture of the sphenoparietal, sphenofrontal, and coronal sutures.
Fontanel and suture widths are determined by a balance between the growth of the calvaria and brain (Figure 2). The flexible sutures allow for molding during birth, as well as both prenatal and postnatal brain growth. The brain grows at its fastest rate during infancy and is about 66% of adult size by age 2 years.2 The cranial vault does not have intrinsic growth potential and will not expand without growth of the brain, as is seen in cases of primary microcephaly or poor growth related to perinatal injury (secondary microcephaly).3 Normally the processes of brain and calvarial growth are tightly linked and regulated, but there are conditions in which this balance is not maintained.
Although the majority of calvarial sutures remain patent into the second decade, the metopic suture normally fuses during infancy, usually within the first 3 to 9 months of life.4,5 Craniosynostosis results from premature closure of the sutures, a pathologic event that normally occurs in utero. Providers must recognize this condition during early infancy so that patients can be referred to a craniofacial center for timely management.6 Infants with craniosynostosis require cranial vault surgery to restore sufficient room for brain growth and prevent increased intracranial pressure (ICP) and developmental delay.
Numerous investigators have measured fontanels of neonates to determine the normal range. In the traditional measurement method, researchers averaged the length (anterior-posterior dimension) and width (transverse dimension) of the fontanel.7 Others have used the diagonal method, in which the diameter of the midpoints of the opposing frontal and parietal bones are measured and again averaged.8 Measurements of anterior fontanels in healthy newborns, including only term infants, can vary considerably (Figure 3).7-13
In 1972, Popich and Smith developed the first normal distribution of anterior fontanel sizes at birth and during the first year of life for Caucasian infants.7 These investigators used the traditional method and measured a mean anterior fontanel size of 2.1 cm (range, 0.6 cm–3.6 cm) from a group of 201 term Caucasian infants. It is significant to note that even infants with measurements that were very small had no underlying problems. Another researcher has shown that African American infants had larger fontanels than Caucasians by measuring fontanels in 293 African American and 73 Caucasian neonates.9
Differences in fontanel size based on ethnicity have been confirmed by other groups, with larger mean measurements of fontanels reported for infants of Hispanic, Nigerian, and Chinese descent.8,12,14,15 Although measuring the fontanel before 24 to 48 hours of age is likely to show differences related to molding during birth, in measuring fontanels from term and preterm infants at corrected gestational age of term, researchers did not find significantly different measurements. Following this group of infants over 24 months, they concluded that prematurity does not contribute to differences in fontanel size at age 2 years.13 Similarly, differences in fontanel size have not been consistently correlated with sex. In conclusion, there is a range of normal size of anterior fontanels in newborns within and among infants of different ethnic backgrounds, but gestational age at birth and sex are not associated with significant differences in fontanel size.
Several studies have measured the size of the anterior fontanel at various times during the first 12 to 24 months of life. These consistently report that the size of the fontanel often increases during the first month of life before it begins to close. The time when the fontanel is too small to be measured by physical exam (and is considered closed) is extremely variable (Figure 4), but a small percentage of anterior fontanels of normal children are closed by age 3 months, 10% by 6 months, 25% to 50% by 12 months, and 98% to 100% are closed by 24 months.13-16 A mean closure time of 13 to 14 months has been reported by several studies.
Various factors influence the size of the fontanel and its quality when palpated. The Table summarizes disorders that affect fontanel size. These disorders are generally related to problems of skeletal morphogenesis, factors related to increased ICP, and associations with syndromes.
The size of the anterior fontanel reflects the balance between growth of the brain and the calvaria (Figure 2). Anterior fontanel size may be smaller than expected when associated with primary microcephaly, an underlying brain malformation such as holoprosencephaly, hypoxic event (secondary microcephaly), or other conditions associated with slow brain growth. In addition anterior fontanel size reflects skeletal morphogenesis. Thyroid hormones are involved in the regulation of bone growth and resorption, and disruption of this balance affects the calvarial bones as well as other parts of the skeleton. Hyperthyroidism may accelerate skeletal development and cause a smaller anterior fontanel, and severe thyrotoxicosis has resulted in craniosynostosis.17,18 Craniosynostosis may also affect anterior fontanel size and shape when the metopic, coronal, or sagittal sutures are involved. Rather than the usual diamond shape of the fontanel that can be palpated when all sutures are patent, there is often blunting on the side of the suture that has fused. In cases of craniosynostosis, however, characteristic head shape differences allow for a clinical diagnosis.3
Many conditions are associated with large fontanels or delayed closure of the anterior fontanel. Infants with hypothyroidism have been recognized for decades to have wider-than-expected fontanels because thyroid hormones are involved in bone growth.19 Infants with rickets or malnutrition may have delayed bone mineralization and larger fontanels. A number of other skeletal disorders are associated with a large fontanel and delayed closure of the fontanel, including hypophosphatasia, parietal foramina syndrome, osteogenesis imperfecta, and achondroplasia.
In children with conditions that impact the entire skeleton, a clinical exam may reveal short stature and/or disproportionate growth, limb bowing, or fractures. Skeletal surveys may prove diagnostic. Additionally assessment of thyroid hormone levels, calcium, phosphate, alkaline phosphatase, and vitamin D levels can serve as adjunct to history and exam. Trisomies (13, 18, and 21) have also been associated with enlarged fontanels and are often detected during the second trimester.20,21 For these children, characteristic findings and structural anomalies provide clues to diagnosis until chromosome studies are completed. Peroxisome biogenesis disorders, including Zellweger syndrome, should be suspected in a hypotonic infant who presents with large anterior fontanel and splayed sutures.22
Congenital rubella and syphilis may also be associated with large fontanels as can prenatal exposures of various drugs, including angiotensin-converting enzyme inhibitors, methotrexate, fluconazole, hydantoin, and primidone.23 Several genetic syndromes also present with large fontanels. These include Beckwith-Wiedemann syndrome (macroglossia, omphalocele, ear creases), cleidocranial dysplasia (brachycephaly, flat midface, hypoplastic clavicles, large fontanel), and Russell-Silver syndrome (triangular face, short stature, clinodactyly), among others. Infants with increased ICP, due to a variety of causes including hydrocephalus, will also present with large fontanels, particularly when increased ICP has been the result of a subacute cause. Benign macrocephaly often manifests with a large fontanel in addition to a larger-than-expected head circumference.
Much is known about the molecular mechanisms that maintain the tightly controlled regulation of calvarial growth. When the balance between brain and calvarial growth is not maintained, craniosynostosis may result. Fibroblast growth factor (FGF) signaling plays an essential role in regulating skeletal development. Several mutations in FGF receptors (mainly FGFR1, FGFR2, and FGFR3) are associated with multisuture craniosynostosis syndromes.
Cleidocranial dysplasia is another example of a disease caused by disruption in regulation of bone formation.24 This syndrome is characterized by a large fontanel, midface hypoplasia, hypoplastic or absent clavicles, and abnormal dentition. Cleidocranial dysplasia is caused by a mutation RUNX2, a transcription factor that regulates several genes controlling bone formation. Although loss of function of RUNX2 results in cleidocranial dysplasia and characteristic bone loss, increased function of RUNX2 results in craniosynostosis. The TWIST1 gene encodes a transcription factor that normally represses RUNX2 during bone formation. Patients with Saethre-Chotzen syndrome have TWIST1 mutations that cause functional haploinsufficiency, resulting in activation (derepression) of RUNX2 and therefore craniosynostosis after tipping the bone balance toward excessive bone formation.25 Genomic duplication of RUNX2 has also been found to result in craniosynostosis.26
The fullness of an infant’s fontanel is a clue to the hydration status. A sunken fontanel suggests dehydration, whereas a tense or bulging fontanel should alert the examiner to consider increased ICP. Intracranial hypertension is generally caused by pathologies that result in cerebral edema, increased cerebral blood volume, and changes in cerebrospinal fluid (CSF) dynamics resulting in either increased secretion or impaired absorption or drainage of CSF (eg, hydrocephalus, mass effect from a tumor, intracranial abscess, hemorrhage, pseudotumor cerebri). Infections can also cause a bulging fontanel, including meningitis, encephalitis, shigella, mononucleosis, or others.27 Edema and diffuse brain swelling, as seen with hypoxic-ischemic encephalopathy or trauma, also will increase ICP and result in a bulging fontanel.
The posterior fontanel is normally less than 1 cm at the time of birth and is no longer palpable by 8 weeks. A posterior fontanel that feels larger than expected should alert the provider to all the conditions described herein that could also cause an enlarged anterior fontanel. An additional genetic cause of an increased posterior fontanel includes parietal foramina syndrome. This syndrome is autosomal dominant with a prevalence of 1:15,000 to 1:25,000. Loss of function mutations in 2 homeobox genes are currently known to be associated with this syndrome, ALX4 and MSX2.28,29 Normally notches in the parietal bones are obliterated by the fifth month of gestation, after emissary veins pass through the bone.30 Delayed ossification around these notches, as seen in parietal foramina syndrome, may be associated with meningeal, cortical, or vascular malformations of the posterior fossa.
A proper skull exam should include palpation of the anterior and posterior fontanels with attention to size, shape, and fullness, and palpation of the entire skull. Providers should note whether there is ridging over sutures or skull defects, and fontanels should be examined with the infant in both upright and supine positions. The skull should also be observed for overall shape. In addition to looking at the infant from the front and sides, it is important to observe the skull shape from above, particularly to note any asymmetries in ear position and any flattening of the skull posteriorly, as well as from behind so the levelness of the skull base can be assessed. (One of the clinical findings associated with lambdoid synostosis is an asymmetric skull base, in which the ipsilateral side will be lower than the unaffected side because the synostosis restricts growth.) Repeating skull exams in a systematic manner will help pediatricians feel a range of fontanels as well as notice differences that may be normal, such as a ridge over the metopic suture when it is closing and an occipital prominence, particularly after breech positioning or associated with a persistent mendosal suture.31 Figure 5 provides an algorithm for evaluating large or small fontanels depending on head shape and size.
In cases in which the skull or fontanel feels abnormal, several options are available for imaging studies. Depending on the age of the infant, a cranial ultrasound may be used to assess intracranial mass, hemorrhage or abnormal extra-axial fluid, and ventricular size. Although the size of the fontanel is variable, after age 4 months the reliability of this study decreases sharply. Some centers have the ability to use cranial ultrasound to determine whether sutures have fused prematurely, but this is dependent on user experience.32
Skull radiographs are rarely useful for evaluating skull abnormalities because of the poor mineralization of the infant skull, the overlapping bone fronts of the coronal and lambdoid sutures, and the inability to visualize soft tissue if there is a concern about an intracranial abnormality.
Magnetic resonance imaging (MRI) is the preferred study for evaluating intracranial abnormalities, ventricular size, and grey- and white-matter abnormalities. This study requires sedation, however, and does not provide good imaging of mineralized tissues. Many centers use HASTE (Half-Fourier Acquisition Single-Shot Turbo Spin Echo) MRI to evaluate fluid spaces. Although this study has the benefit of not requiring sedation, the images cannot be used to evaluate intracranial structures as completely as on a full MRI.
Computed tomography (CT) scans, particularly 3-D CT scans, are the most helpful way to evaluate skull differences, including craniosynostosis and defects in the bone. A CT scan also provides information about ventricular size, size of the subarachnoid space, hemorrhage, and intracranial masses. Many pediatric centers offer low-dose CT scans, from which 3-D images can be reconstructed for superior visualization of bone at a significantly lower dose of radiation.
If the anterior fontanel is not palpable at an early age, providers should closely examine head shape and assess development and head circumference. An infant with a normal head shape, size, and growth should reassure the primary care provider that an anterior fontanel that is small or not palpable at an early age has no pathology and can be followed at regular well-child visits. If there are other abnormalities or reasons for concern, providers should consider imaging and referral to a craniofacial center for further evaluation.
Referral to a craniofacial center as early as possible in cases of possible single-suture craniosynostosis is recommended. Craniofacial specialists will evaluate the infant, determine the optimal timing for imaging to confirm the diagnosis, and aid with surgical planning, as well as discuss the timing of surgery with the family. In cases of multisuture craniosynostosis, brain growth will direct skull growth in whatever direction the sutures are patent. The resulting head shape can be very abnormal, sometimes causing kleeblattschädel, or cloverleaf skull deformity, in which brain growth occurs mainly in the direction of the squamosal sutures that only rarely close during infancy. Infants with multisuture synostosis need close monitoring during infancy and childhood for problems related to increased ICP and airway insufficiency.
The pediatrician’s handshake is an essential part of the infant exam, but it is also important to examine skull shape and size at the same time. Because there is a wide range of normal anterior fontanel sizes during the first year, size alone is not sufficient to diagnose a pathologic condition. The exam of the infant skull shape provides valuable information about whether the infant may have an underlying problem, such as craniosynostosis. The fontanel provides a window into what may be occurring in the brain, but providers should evaluate the fontanel in the context of skull shape, size, and growth. If these other parameters are normal, there are no conditions that can cause an abnormal fontanel that require further intervention or evaluation.
1. Haslam R. The nervous system. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics, 18th ed. Philadelphia, PA: Saunders; 2004:2434-2435.
2. World Health Organization. Child growth standards. Head circumference-for-age. http://www.who.int/childgrowth/standards/hc_for_age/en/. Accessed September 30, 2013.
3. Cunningham ML, Heike CL. Evaluation of the infant with an abnormal skull shape. Curr Opin Pediatr. 2007;19(6):645-651.
4. Vu HL, Panchal J, Parker EE, Levine NS, Francel P. The timing of physiologic closure of the metopic suture: a review of 159 patients using reconstructed 3D CT scans of the craniofacial region. J Craniofac Surg. 2001;12(6):527-532.
5. Cohen MM. Sutural biology. In: Cohen MM Jr, MacLean RE, eds. Craniosynostosis: Diagnosis, Evaluation, and Management, 2nd ed. New York: Oxford University Press; 2000:11-23.
6. McCarthy JG, Warren SM, Bernstein J, et al; Craniosynostosis Working Group. Parameters of care for craniosynostosis. Cleft Palate Craniofac J. 2012;(49 suppl):1S-24S.
7. Popich GA, Smith DW. Fontanels: range of normal size. J Pediatr. 1972;80(5):749-752.
8. Jackson GL, Hoyer A, Longenecker L, Engle WD. Anterior fontanel size in term and late preterm Hispanic neonates: description of normative values and an alternative measurement method. Am J Perinatol. 2010;27(4):307-312.
9. Faix RG. Fontanelle size in black and white term newborn infants. J Pediatr. 1982;100(2):304-306.
10. Srugo I, Berger A. Anterior fontanelle size in healthy Israeli newborn infants. Isr J Med Sci. 1987;23(11):1137-1139.
11. Mir NA, Weislaw R. Anterior fontanelle size in Arab children: standards for appropriately grown full term neonates. Ann Trop Paediatr. 1988;8(3):184-186.
12. Adeyemo AA, Olowu JA, Omotade OO. Fontanelle sizes in term neonates in Ibadan, Nigeria. West Afr J Med. 1999;18(1):55-59.
13. Duc G, Largo RH. Anterior fontanel: size and closure in term and preterm infants. Pediatrics. 1986;78(5):904-908.
14. Omotade OO, Kayode CM, Adeyemo AA. Anterior fontanelle size in Nigerian children. Ann Trop Paediatr. 1995;15(1):89-91.
15. Chang BF, Hung KL. Measurements of anterior fontanels in Chinese. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1990;31(5):307-312.
16. Pedroso FS, Rotta N, Quintal A, Giordani G. Evolution of anterior fontanel size in normal infants in the first year of life. J Child Neurol. 2008;23(12):1419-1423.
17. Rasmussen SA, Yazdy MM, Carmichael SL, Jamieson DJ, Canfield MA, Honein MA. Maternal thyroid disease as a risk factor for craniosynostosis. Obstet Gynecol. 2007;110(2 pt 1):369-377.
18. Gogakos AI, Duncan Bassett JH, Williams GR. Thyroid and bone. Arch Biochem Biophys. 2010;503(1):129-136.
19. Smith DW, Popich G. Large fontanels in congenital hypothyroidism: a potential clue toward earlier recognition. J Pediatr. 1972;80(5):753-756.
20. Jones KL. Smith’s Recognizable Patterns of Human Malformation, 6th ed. Philadelphia, PA: WB Saunders; 2005:872-873.
21. Paladini D, Sglavo G, Penner I, Pastore G, Nappi C. Fetuses with Down syndrome have an enlarged anterior fontanelle in the second trimester of pregnancy. Ultrasound Obstet Gynecol. 2007;30(6):824-829.
22. Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Peroxisome biogenesis disorders, Zellweger syndrome spectrum. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews. Seattle, WA: University of Washington; 1993-2013. http://www.ncbi.nlm.nih.gov/books/NBK1448/. Published December 12, 2003. Updated May 10, 2012. Accessed September 30, 2013.
23. Graham JM. Skull. In: Stevenson RE, Hall JG, eds. Human Malformations and Related Anomalies, 2nd ed. New York: Oxford University Press; 2006:221-265.
24. Mendoza-Londono R, Lee B. Cleidocranial dysplasia. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews. Seattle, WA: University of Washington; 1993-2013. http://www.ncbi.nlm.nih.gov/books/NBK1513/. Published January 3, 2006. Updated August 29, 2013. Accessed September 30, 2013.
25. Gallagher ER, Ratisoontorn C, Cunningham ML. Saethre-Chotzen syndrome. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews. Seattle, WA: University of Washington; 1993-2013. http://www.ncbi.nlm.nih.gov/books/NBK1189/. Published May 16, 2003. Updated June 14, 2012. Accessed September 30, 2013.
26. Mefford HC, Shafer N, Antonacci F, et al. Copy number variation analysis in single-suture craniosynostosis: multiple rare variants including RUNX2 duplication in two cousins with metopic craniosynostosis. Am J Med Genet A. 2010;152A(9):2203-2210.
27. Kiesler J, Ricer R. The abnormal fontanel. Am Fam Physician. 2003;67(12):2547-2552.
28. Mavrogiannis LA, Antonopoulou I, Baxová A, et al. Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects. Nat Genet. 2001;27(1):17-18.
29. Wuyts W, Reardon W, Preis S, et al. Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna. Hum Mol Genet. 2000;9(8):1251-1255.
30. Wilkie AOM, Mavrogiannis LA. Enlarged parietal foramina. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews. Seattle, WA: University of Washington; 1993-2013. http://www.ncbi.nlm.nih.gov/books/NBK1128/. Published March 20, 2004. Updated November 8, 2012. Accessed September 30, 2013.
31. Gallagher ER, Evans KN, Hing AV, Cunningham ML. Bathrocephaly: a head shape associated with a persistent mendosal suture. Cleft Palate Craniofac J. 2013;50(1):104-108.
32. Sze RW, Hopper RA, Ghioni V, et al. MDCT diagnosis of the child with posterior plagiocephaly. AJR Am J Roentgenol. 2005;185(5):1342-1346.
DR GALLAGHER is assistant professor of pediatrics, Doernbecher Children’s Hospital, and director of the Craniofacial Disorders Program, Oregon Health and Science University, Portland. DR HING is associate professor of pediatrics, University of Washington School of Medicine, Children’s Craniofacial Center, Seattle Children’s Hospital, Seattle. DR CUNNINGHAM is professor, Department of Pediatrics, chief, Division of Craniofacial Medicine, University of Washington School of Medicine, and medical director, Children’s Craniofacial Center, Seattle Children’s Hospital, Seattle. The authors have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.