Journal of Perinatology (2008) 28, 313–315 r 2008 Nature Publishing Group All rights reserved. 0743-8346/08 $30 www.nature.com/jp IMAGING CASE BOOK Miller–Dieker syndrome, type 1 lissencephaly TE Herman and MJ Siegel Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Journal of Perinatology (2008) 28, 313–315; doi:10.1038/sj.jp.7211920 bitemporal shallowness. The ears were low set. Retromicrognathia, and microphthalmia, more marked on the left, were also present. Case presentation The child had a cranial sonogram (Figure 1) and cranial magnetic A 1910 g infant was born at 41-weeks gestation to a 19-year-old resonance imaging (Figure 2). gravida 1 mother after a pregnancy complicated by hydramnios and poor fetal movement. The child was delivered by a cesarean section because of fetal decelerations with labor. Severe intrauterine Denouement and discussion growth retardation was present with the infant’s weight, length and The cranial sonogram demonstrated an abnormally smooth brain head circumference all less than the tenth percentile for gestational with no gyration or sulcation with a wide, shallow sylvian fissure age. The patient’s head demonstrated a wasted appearance with creating a figure-of-8 appearance. The absence of all gyri is Figure 1 (a) Coronal cranial sonogram at the level of the third ventricle demonstrating a figure-of-8 appearance of the brain with wide sylvian fissure and with no sulci or gyri. (b) Sagittal right lateral cranial sonogram demonstrating absence of gyri over the ipsilateral hemisphere. (c) Right sagittal sonogram demonstrating echogenic linear thalamostriate vessels (arrow). The left hemisphere had a similar appearance. (d) Sagittal left lateral sonogram demonstrating absent sulci, gyri. Correspondence: Dr TE Herman, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St Louis, MO 63110, USA. E-mail: [email protected] Received 5 November 2007; accepted 28 November 2007 Miller–Dieker syndrome TE Herman and MJ Siegel 314 Figure 2 (a) T2-weighted coronal MRI and (b). T2-weighed axial MRI views of the brain. There is a thickened cortex without gyri or sulci and a figure-of-8 appearance of the brain with a wide, shallow sylvian fissure (arrows). (c) Posterior coronal T2-weighed images demonstrating a left parafalcine arachnoid cyst (AC). (d) T1-weighted image through the orbits demonstrating left microphthalmia (arrow). MRI, magnetic resonance imaging. referred to as lissencephaly (smooth brain).1 The corpus callosum migrational abnormality with a thickened, smooth cerebral cortex, was incompletely formed. In addition, at cranial sonography there failure of opercularization (closure of the sylvian fissure to cover were echogenic thalamostriate vessels, or so-called thalamostriate the insula), colprocephaly and occasional calcifications of the vasculopathy. The magnetic resonance imaging demonstrated the septum pellucidum.2 At birth, there is usually a normal head partial agenesis of the corpus callosum, lissencephaly, left circumference or a head circumference within 2 s.d. of normal.1 microphthalmia and a small arachnoid cyst along the parafalcine Four genes are known to be associated with classical lissencephaly: left parietooccipital cortex. The cerebral cortex, usually measuring LIS1, DCX, ARX and TUBA3. LIS1 gene, located at 17p3, is known less than 3 mm, measured over 5 mm. The colprocephaly and to be necessary for the neuronal precursors to undergo normal incomplete opercularization with wide shallow sylvian fissures were neuronogenesis and migration. Miller–Dieker syndrome is noted to produce a figure-of-8 appearance to the brain. This associated with 17p3 deletions, usually with complete absence of appearance is typical of classical or type 1 lissencephaly.1,2 the LIS1 gene, and it is the most common cause of classical Chromosomal analysis of the infant demonstrated a deletion of lissencephaly. Norman–Roberts syndrome is an autosomal 17p3, confirming a diagnosis of Miller–Dieker syndrome with recessive condition associated with type 1 lissencephaly, but with type 1 lissencephaly. severe microcephaly (less than 3 s.d. below normal). Type 2 Lissencephaly is a rare condition. Three types have been lissencephaly, so-called cobblestone lissencephaly, has a granular described.1 Type l or classical lissencephaly is a neuronal surface with effacement of gyri. It is found in the autosomal Journal of Perinatology Miller–Dieker syndrome TE Herman and MJ Siegel 315 recessive conditions: Walker–Warbury syndrome and seizures (90% by 1 year of age) and profound neurodevelopmental Fukuyama syndrome. Type 2 lissencephaly is associated with retardation. O-glycosylation enzyme defects resulting in abnormal laminin. The differential diagnosis of Miller–Dieker syndrome includes Type 3 lissencephaly is associated with severe microcephaly and other syndromes, with facial dysmorphism, microcephaly, is a neurodegenerative process with abnormal apoptosis. It seizures and hypotonia, such as Cornelia de Lange syndrome, occurs in the Neu–Laxova and Encha Razavi Larroche Wolf–Hirschorn syndrome, Smith–Lemli–Opitz syndrome and syndromes. Zellweger syndrome.8 However, none of these have lissencephaly. The clinical appearance of children with Miller–Dieker Chromosomal analysis to show a 17p3 deletion reliably excludes syndrome is characteristic. There is a high forehead, often with other causes of type 1 lissencephaly. The syndromes with types 2 vertical furrows, due to an unusual ability to wrinkle the skin of and 3 lissencephaly have associated typical manifestations and can the forehead.1,3 The ears are low set and the eyes widely separated. be usually easily excluded. Type 2 lissencephaly is a specific The upper lip is thickened, but with a thin vermillion border. There component of Walker–Warbur syndrome, Fukuyama congenital is an elongated philtrum with rounded pillars. There is bitemporal muscular dystrophy and some other familial syndromes. Type 3 narrowing and the nose is short and anteverted.4 The degree of lissencephaly occurs in association with stippled epiphyses and agyria in lissencephaly may vary and has been stratified by Dobyns metacarpal-phalangeal bone dysplasia. into six different grades of severity.1,5 Grade 1, as occurred in this Treatment of Miller–Dieker syndrome is usually antiepileptic patient, is complete agyria. Grade 2 has some minimal gyration in medications and support. Death usually occurs within the first year the frontal region. The remaining grades have decreasing extent of life.6 agyria and increased pachygyria or abnormally broad gyri. The magnetic resonance imaging and sonographic appearance References of the brain in this patient are characteristic of Miller–Dieker syndrome. However, several additional imaging features were 1 Verloes A, Elmaleh M, Gonzales M, Laquerriere A, Gressens P. Lissence´phalies: aspects present in this patient not described, to our knowledge, in other cliniques et ge´ne´tiqes. Rev Neurol (Paris) 2007; 163: 533–547. 2 Williams JP, Joslyn JN. Lissencephaly: computed tomographic diagnosis. J Computed patients with Miller–Dieker syndrome. These include the presence Tomography 1983; 7: 141–144. of thalamostriate vasculopathy, arachnoid cyst and 3 Dobyns WB, Stratton RF, Parke JT, Greenberg F, Nussbaum RL, Ledbetter DH. microophthalmia. Thalamostriate vasculopathy on transcranial Miller–Dieker syndrome: lissencephaly and monosomy 17p. J Pediatrics 1983; 102: sonography has been reported in TORCH infections, particularly 552–564. cytomegalovirus infection, trisomy 13, translocation chromosome 4 Allanson JE, Ledbetter DH, Dobyns WB. Classical lissencephaly syndromes: does the face 11 and various other metabolic and dysmorphic syndromes.6 reflect the brain? J Med Genet 1998; 35: 920–923. 5 Uyanik G, Morris-Rosendahl DJ, Stiegler J, Klapecki J, Gross C, Berman Y et al. Location Intracranial subarachnoid cysts are usually supratentorial, and type of mutation in the LIS1 gene do not predict phenotypic severity. Neurology but primarily in the temporal fossa and not parafalcine as in 2007; 69: 442–447. this patient.7 Although microphthalmia is common in type 2 6 EI Ayoubi M, de Bethmann O, Monset-Couchard M. Lenticulostriate Echogenic lissencephaly syndromes, it is not a frequent finding in vessels: clinical and sonographic study of 70 neonatal cases. Pediatr Radiol 2003; 33: Miller–Dieker syndrome. 697–703. 7 Osborn AG, Preece MT. Intracranial cysts: radiologic-pathologic correlation and imaging The clinical presentation of children with grade 1 type 1 approach. Radiology 2006; 239: 650–664. lissencephaly is also usually typical. They are hypotonic at birth, 8 Rivas MV, Alvarez LA, Altman N. Pictoral review: Miller Dieker syndrome. 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