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Year : 2022  |  Volume : 70  |  Issue : 2  |  Page : 794--795

The “Z”-Shaped Brainstem—A Tale of Two Distinct Gene Mutations

Chinky Chatur1, Ankit Balani2, Kshitij Mankad1,  
1 Department of Paediatric Neuroradiology, Great Ormond Street Hospital for Children, London, UK
2 Lysholm Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, UCLH Foundation Trust, London, UK

Correspondence Address:
Dr. Ankit Balani
Lysholm Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, UCLH Foundation Trust, London

How to cite this article:
Chatur C, Balani A, Mankad K. The “Z”-Shaped Brainstem—A Tale of Two Distinct Gene Mutations.Neurol India 2022;70:794-795

How to cite this URL:
Chatur C, Balani A, Mankad K. The “Z”-Shaped Brainstem—A Tale of Two Distinct Gene Mutations. Neurol India [serial online] 2022 [cited 2022 Aug 11 ];70:794-795
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Full Text

Dear Sir,

The Z-shaped brainstem has been commonly associated and described with congenital muscular dystrophy. We read with a great deal of interest, the manuscript titled “Z-shaped brainstem and other magnetic resonance imaging findings in congenital muscular dystrophy” by DM Cecil et al. in the May–June 2016 issue of Neurology India, Volume 64, Issue 3.[1] The manuscript is intelligently written with self-explanatory images describing imaging findings of congenital muscular dystrophy, in particular, Z-shaped brainstem which refers to hypoplastic pons with the small ventral notch.

Sir, we would, hereby, like to make a pertinent contribution based on our recent experience of two patients with two different genetic mutations and, hence, different diagnoses with similar morphology of brainstem, thus, emphasizing that Z-shaped brainstem is not an entity exclusively reserved for congenital muscular dystrophy.

A female child was born to non-consanguineous parents by spontaneous vaginal delivery at term with meconium-stained liquor. In view of poor respiratory effort and bradycardia, she was resuscitated and put on ventilatory support immediately after birth. She had an episode of generalized tonic-clonic seizure on day 1 of life which was controlled with phenobarbitone. Neurological examination showed reduced muscle tone without muscle weakness. Deep tendon reflexes were present in all four limbs, however, were difficult to elicit. Biochemical evaluation including whole blood count, very-long-chain fatty acids, creatinine kinase, cholesterol, serum calcium, magnesium, phosphate, liver function test, and biotinidase was normal.

Magnetic resonance imaging (MRI) done on day 7 of life in view of perinatal hypoxia showed “Z”-shaped or kinked brainstem which was hypoplastic, had partial midline cleft and asymmetrical focal bulges involving the right side of the medulla oblongata and left hemipons. Cerebellum was small and dysplastic. Also, there were fused basal ganglia structures with dysgenesis of anterior limbs of internal capsules (“absent/dysgenetic ALIC sign”), diffuse bilateral perisylvian dysgyria-polymicrogyria and hypoplastic corpus callosum [Figure 1]. Imaging findings were suggestive of a likely diagnosis of tubulinopathy.{Figure 1}

The differentials included dystroglycanopathies, however, in view of the hypoplastic corpus callosum, absent/dysgenetic anterior limbs of internal capsules, normal creatine kinase and normal electromyography, they were unlikely. Genetic testing was offered in view of suspicion of tubulinopathies which confirmed heterozygous mutation in the TUBA1A gene (c.691A>C).

Tubulinopathies, which are associated with mutations in the tubulin genes, represent a spectrum of complex brain malformations characterized by multiple cortical and subcortical abnormalities of the corpus callosum, brainstem, basal ganglia, internal capsules, and white matter.[2],[3]

Our second case is that of a male child who was diagnosed to have ventriculomegaly on antenatal ultrasound. He was born to non-consanguineous parents by emergency cesarean section at 38 weeks 6 days due to non-progression of labor. His APGAR scores were 5 at 1 min and 6 at 5 min. Neurological examination showed that he had at least antigravity strength in all joints of all limbs and a normal tone with no pyramidal signs. Deep tendon reflexes were present with no clonus and no abnormal posturing. His breathing pattern was regular and normal. MRI done on day 3 of life showed markedly hypoplastic pons with small ventral cleft giving “Z”-shaped appearance to the brainstem, cobblestone cortical malformation in bilateral frontal and perisylvian regions, hypoplastic cerebellum with few microcysts, absence of the septum pellucidum, and hypoplastic corpus callosum [Figure 2]. The imaging findings suggested a diagnosis of an alpha dystroglycanopathy. Ophthalmological examination showed bilateral microphthalmia (corneal diameters of 8 mm), bilateral central vitreoretinal dysplasia and bilateral persistent fetal vasculature. The aforementioned findings pointed toward the diagnosis of Walker-Warburg/muscle-eye brain disease. Genetic testing revealed a homozygous mutation in the POMGnT1 gene with c. 303delinsCTp. (Glu102Ter) pathogenic sequence variant, thus, confirming the diagnosis of Walker-Warburg syndrome.{Figure 2}

Thus, we present a tale of two distinct genetic mutations of TUBA1A and POMGnT1 genes, responsible for different pathologies, that is, tubulinopathy and dystroglycanopathy in two children with a common imaging finding of “Z”-shaped or kinked brainstem.

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1Cecil DM, Chaturvedi A, Kapoor D. Z-shaped brainstem and other magnetic resonance imaging findings in congenital muscular dystrophy. Neurol India 2016;64:577-8.
2Bahi-Buisson N, Poirier K, Fourniol F, Saillour Y, Valence S, Lebrun N, et al. The wide spectrum of tubulinopathies: What are the key features for the diagnosis? Brain 2014;137:1676-700.
3Goncalves FG, Freddi TA, Taranath A, Lakshmanan R, Goetti R, Feltrin FS, et al. Tubulinopathies. Top Magn Reson Imaging 2018;27:395-408.