Megalencephaly is defined as a hyperplastic or hypertrophic disorder of brain parenchyma leading to an increase in brain size. It is therefore commonly associated with macrocephaly, defined as an increase in cranial size. It is usually symmetric but may be unilateral, and borderline ventriculomegaly is frequently seen. The aetiology is unknown, but the condition is seen in association with a variety of syndromes. However, the majority of cases are isolated, benign, and familial (autosomal dominant).


The diagnosis is suspected in the presence of macrocephaly (head circumference in the transthalamic plane > 2 standard deviations above the mean), and is one of exclusion. Several other intracranial anomalies will give rise to macrocephaly, and these include hydrocephalus, holoprosencephaly, hydranencephaly, porencephaly, and intracranial tumours; in contrast to these, with benign familial megalencephaly the intracranial architecture will appear normal, although there may be borderline ventriculomegaly. Unilateral megalencephaly may be suspected if there is asymmetry of the cerebral hemispheres and displacement of the falx in association with unilateral ventriculomegaly. Hemihypertrophy of the body may also be present. Due to the large number of associated syndromes a careful systemic survey should be undertaken. For example, thanatophoric dysplasia (micromelia) and hypochondroplasia (rhizomelia) are both associated with megalencephaly. For the same reason, karyotyping is recommended due to the associations with Klinefelterís syndrome (47, XXY), Fragile X, and occasional partial trisomies (chromosome 1[q42-qter] trisomy). In the absence of any sonographic or karyotypic abnormality, the prognosis is favourable, although developmental studies have suggested an increased risk of learning disability despite average intelligence.

Differential Diagnosis

Other causes of macrocephaly require exclusion: Massive hydrocephalus Hydranencephaly Porencephaly Alobar holoprosencephaly Intracranial tumours Intracranial haemorrhage The diagnosis of megalencephaly should be considered when a large head is found with no intracranial abnormality.

Sonographic Features

Macrocephaly (head circumference > 2 SD above mean).
Borderline ventriculomegaly may be present.
Normal intracranial architecture.
Anomalies in other systems should be excluded.

Associated Syndromes

  • Achondroplasia
  • Acrocallosal
  • Anophthalmia
  • Anophthalmia-cleft lip/palate
  • Ataxia-telangiectasia
  • Atkin: Coffin-Lowry-like facies
  • Bannayan-Zonana
  • Basal cell nevus
  • Behmel
  • Brachytelephalangy-anosmia
  • Cerebrofaciothoracic
  • Chitayat
  • Chromosome: (1)(q42ˆqter) trisomy
  • Chromosome: del(5)(q35.3)
  • Costello
  • Cowden
  • Cronkite-Canada, infantile
  • Epidermal (linear) nevus syndrome
  • Fragile X
  • Fryns
  • Glutaryl-CoA-dehydrogenase deficiency
  • Greig
  • Heide
  • Hypochondroplasia
  • Hypomelanosis of Ito
  • Klinefelter
  • Klippel-Trenaunay-Weber
  • Laxova
  • LeMarec
  • Lujan: marfanoid
  • Megalencephaly, benign familial
  • Megalencephaly-hamartomas
  • Moreno
  • Mžller: cerebral malformation-hypertrichosis-fingers
  • Nasopharyngeal teratom
  • Neuro-facio-digito-renal
  • Neurofibromatosis
  • Noonan syndrome
  • Noonan-cardiofaciocutaneous variant
  • Noonan-neurofibromatosis
  • Osteopathia striata-cranial sclerosis
  • Parietal foramina-clavicular hypoplasia
  • Pena-Shokeir without intrauterine growth retardation
  • Perlman
  • Richieri-Costa
  • Riley-Smith
  • Robinow fetal face
  • Ruvalcaba-Myhre-Smith
  • Sotos: Blackett variant
  • Sotos
  • Sotos: Goldstein variant
  • Subcutaneous thickness-coarse facies
  • Thanatophoric dysplasia
  • Toriello
  • Van Benthem
  • Weaver
  • Wiedemann


Ramirez M, Wilkins I, Kramer L, Slopis J, Taylor SR Prenatal diagnosis of unilateral megalencephaly by real-time ultrasound Am J Obstet Gynecol 170: 1384-1385
DeRosa R, Lenke RR, Kurczynski TW, Persutte WH, Nemes JM In utero diagnosis of benign fetal macrocephaly Am J Obstet Gynecol 161: 690-692