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 Table of Contents  
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 72-74

Benign megalencephaly

Department of Pediatric Dentistry, Government Dental College and Hospital, Aurangabad, Maharashtra, India

Date of Submission07-Apr-2021
Date of Acceptance02-Jun-2021
Date of Web Publication26-Dec-2021

Correspondence Address:
Chaitali Hambire
17, Shreekunj, Samadhan Colony, Behind Sessions Court, Aurangabad - 431 001, Maharashtra.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/dypj.dypj_17_21

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Measurement of head circumference 2 standard deviations above the age-related mean is called megalencephaly and macrocephaly. A distinction between these two entities is appropriate for proper clinical workup, overall prognosis, and treatment. Macrocephaly is a nonspecific clinical finding without implications about the underlying cause. Megalencephaly is an increased growth of cerebral structures related to dysfunctional anomalies during the various steps of brain development in the neuronal proliferation and/or migration phases or as a consequence of postnatal abnormal events.

Keywords: Head circumference, large head, macrocephaly, megalencephaly, pediatric

How to cite this article:
Hambire C, Hambire U. Benign megalencephaly. D Y Patil J Health Sci 2021;9:72-4

How to cite this URL:
Hambire C, Hambire U. Benign megalencephaly. D Y Patil J Health Sci [serial online] 2021 [cited 2022 Aug 8];9:72-4. Available from: http://www.dypatiljhs.com/text.asp?2021/9/2/72/333766

  Introduction Top

The head is a system composed of a container, the skull, and the contents being the brain, cerebrospinal fluid (CSF), and blood vessels. According to the Monro-Kellie doctrine, within an intact skull, the sum of the volumes of the brain, CSF, and intracranial blood is constant. To keep the intracranial volume balanced, an increase in the size of one component causes a reduction in one or both of the other two.[1] Majority of the cranial sutures normally remain patent beyond early childhood except the metopic suture, which typically closes in the 1st year of life.[2] The posterior fontanelle generally closes 2 months after birth and the anterior fontanelle by 2 years of age in almost all infants.[3] The newborn brain is reported to weigh about 370 g and increases about 4-fold from infancy to childhood till reaching an adult’s weight of about 1500 g.[4] The measurement of the head (occipitofrontal) circumference is an important part of physical examination in pediatric practice. The occipitofrontal circumference extends from the most prominent part of the glabella to the most prominent posterior area of the occiput.[5] A proper measure of the head circumference should be performed by putting the tape measure along the most prominent diameter of the occiput and the mid forehead. These results of the measurement must be checked with the head circumference growth charts, according to the age, gender, and height parameters.

Difference between megalencephaly and macrocephaly

The normal head circumference measurement at birth is approximately 34.9 cm (13 — inches). Around 1 month of age, this increases up to 38.1 cm (15 inches). By definition, the measurement of head circumference is reported to be two standard deviations (SDs) above the age-related mean or 0.5 cm above the 97th percentile, both in megalencephaly and macrocephaly.[5] Megalencephaly defines an increased growth of cerebral structures related to dysfunctional anomalies during the various steps of brain development in the neuronal proliferation and/or migration phases or as a consequence of postnatal abnormal events that cause excessive cerebral growth. In contrast, in macrocephaly, the increased head circumference is linked to various events that can result in an increase of orbitofrontal head circumference for age including anomalies of bone skull structures, subdural fluid collections, hydrocephalus, intracranial masses, and arteriovenous malformations [Figure 1]. However, both megalencephaly and macrocephaly may coexist in the same individual due to some adverse events. Prognostically, megalencephaly is considered to be more severe than macrocephaly. It has been reported more frequently in the patients suffering from intellective delay, epilepsy, and drug-resistant epilepsy.[6]
Figure 1: Flowchart for differential diagnosis between megalencephaly and macrocephaly

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Physical manifestations associated with megalencephaly and macrocephaly

Physical examination of pediatric patients with megalencephaly and macrocephaly shows large or tense fontanels, enlarged sutures, the sun-setting sign, hypotonia, irritability, or, in older children, neurodevelopment delay, lethargy, and/or seizures.[7]

Associated metabolic disorders

Three groups of metabolic disorders have been suggested to be associated with megalencephaly: defects of the organic acids, metabolic leukoencephalopathies or metabolic encephalopathies, and lysosomal storage diseases.[4] Defects of organic acids include glutaric aciduria type 1 (gene defect GCDH) and L–2-hydroxyglutaric aciduria (gene defect L2HG). Glutaric aciduria type 1 is caused by deficiency of glutaryl-CoA dehydrogenase involved in the pathway of lysine to hydroxylysine and L-tryptophan. Abnormal head circumference is present since birth and is the earliest and most distinctive sign of this disorder. The enzymatic defect causes an accumulation of glutaric acid and 3-hydroxyglutaric acid that interferes in the energetic metabolism and oxidative stress, provoking neuronal impairment. Untreated patients present with dystonic movement disorders in infancy. Metabolic encephalopathies such as Canavan disease is caused by deficiency of aspartoacylase that leads to the accumulation of N-acetylaspartic acid (NAA) in the brain and in white matter. In this disorder, there is a degeneration of myelin in the phospholipid layer that isolates the axon. The NAA in a high concentration results in myelin vacuolization and astrocyte swelling. The clinical features in the infantile form are characterized by a rapidly increasing head circumference, severe hypotonia, and irritability with an onset at around 3–6 months of age. Subsequently, feeding difficulties with poor growth become more evident as the delayed milestones. Hypertonia, joint stiffness, and seizures develop rapidly, and most of the patients die in the first decade of life. Alexander disease has been the first identified primary genetic disorder of astrocytes and is caused by mutations in the gene encoding glial fibrillary acidic protein. Progressive neurological impairment, megalencephaly, and a typical MRI pattern are classically recognized as diagnostic. The brain MRI shows characteristic symmetric and extensive abnormalities with frontal predominance and relative sparing of occipital and temporal white matter.[8],[9] Megalencephalic leukoencephalopathy (MLC) with subcortical cysts associated with MLC1 and HEPACAM gene mutations and leukoencephalopathy with vanishing white matter, which is linked to mutations in EIFB1, EIFB2, EIFB3, EIFB4, and EIFB5 (eukaryote translational initiation factor B1-B5) genes, have been reported in patients presenting an abnormal head circumference. In MLC, the large head may be present at birth, but more often, it appears during the 1st year of life. The degree of abnormal head circumference may reach 4–6 SDs above the average. After the 1st year, the head growth tends to normalize and to stabilize within the 98th percentile. Patients present with hypotonia, cognitive delay, and seizures.[10]

Lysosomal storage diseases such as Tay–Sachs disease manifest clinical signs beginning at the age of 6 months with a progressive delay of the developmental milestones and hypotonia. A large head becomes apparent by 1 year of age due to an abnormal content of the ganglioside GM2, which accumulates in the brain. Short stature, progressive spasticity, and seizures with visual degeneration and deafness are the presenting clinical signs. Cherry red spots at the fundoscopic examination are useful for diagnosis.[7],[8],[9]

  Case Report Top

A 7-year-old boy, an only child born of a nonconsanguineous marriage, reported to the outpatient department for dental examination. During the extraoral examination, it was observed that the child had dolichocephalism along with long and narrow face. The head circumference was 42.5 cm, height was 90 cm, and weight was 20 kg which is below the 3rd percentile for height and weight. He had convex facial profile with broad nasal base. Intraoral examination showed that he had carious primary mandibular second molar of left side associated with pain after food lodgment [Figure 2] and [Figure 3].
Figure 2: View of head from top

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Figure 3: Lateral view

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Birth history was normal and neonatal period uneventful. There were no seizures or paucity of limb movements. His developmental milestones were normal. The family history revealed that his parents were healthy with normal head size and shape. There was no familial history of a head with increased circumference. He had no systemic or metabolic problems. The parents reported that his neurological reports were normal. He was responsive and co-operative. He was diagnosed with benign or idiopathic megalencephaly. He was treated for his dental problems.

  Discussion Top

Megalencephaly is a congenital condition characterized by severe overdeveloped brain size. Several congenital conditions and several molecular mutations may cause megalencephaly, and in most of the cases, they are associated with other cerebral and clinical anomalies. The condition has to be distinguished by the macrocephaly that presents with different clinical situations. In this case, the child was suffering from benign or idiopathic megalencephaly. In this condition, the children have an abnormally large head with no neurological impairment. An increased head circumference is often reported in one or both the parents.[1] These children do not suffer from any cerebral or metabolic disorders. Detailed case history along with proper clinical examination can help us to establish correct diagnoses and guide management.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Winden KD, Yuskaitis CJ, Poduri A. Megalencephaly and macrocephaly. Semin Neurol 2015;35:277-87.  Back to cited text no. 1
Kiesler J, Ricer R. The abnormal fontanel. Am Fam Physician 2003;67:2547-52.  Back to cited text no. 2
Paciorkowski AR, Greenstein RM. When is enlargement of the subarachnoid spaces not benign? A genetic perspective. Pediatr Neurol 2007;37:1-7.  Back to cited text no. 3
Tucker J, Choudhary AK, Piatt J. Macrocephaly in infancy: Benign enlargement of the subarachnoid spaces and subdural collections. J Neurosurg Pediatr 2016;18:16-20.  Back to cited text no. 4
Ono Y, Saito Y, Maegaki Y, Tohyama J, Montassir H, Fujii S, et al. Three cases of right frontal megalencephaly: Clinical characteristics and long-term outcome. Brain Dev 2016;38:302-9.  Back to cited text no. 5
Aslanger AD, Altunoglu U, Aslanger E, Satkın BN, Uyguner ZO, Kayserili H. Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2. Am J Med Genet A 2014;164A: 484-9.  Back to cited text no. 6
Mirzaa GM, Poduri A. Megalencephaly and hemimegalencephaly: Breakthroughs in molecular etiology. Am J Med Genet C Semin Med Genet 2014;166C: 156-72.  Back to cited text no. 7
Medina LS, Frawley K, Zurakowski D, Buttros D, DeGrauw AJ, Crone KR. Children with macrocrania: Clinical and imaging predictors of disorders requiring surgery. AJNR Am J Neuroradiol 2001;22:564-70.  Back to cited text no. 8
Johnson AB. Alexander disease: A review and the gene. Int J Dev Neurosci 2002;20:391-4.  Back to cited text no. 9
Pronk JC, van Kollenburg B, Scheper GC, van der Knaap MS. Vanishing white matter disease: A review with focus on its genetics. Ment Retard Dev Disabil Res Rev 2006;12:123-8.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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