Child with Abnormal Head – Is it Megalencephaly–Polymicrogyria–Polydactyly–Hydrocephalus Syndrome?
Dear Editor, A child presenting with macrocephaly poses a diagnostic dilemma due to its varied etiologies. It has to be investigated, and neuroimaging plays an essential role in it. There are varied imaging phenotypes described (not present in all cases), and in our case, we describe imaging findings in brain and spine – not described earlier – in a genetically proven case of megalencephaly–polymicrogyria–polydactyly hydrocephalus (MPPH) syndrome. Although many heritable or nonheritable causes are identified, few rare syndromes with their genetic basis are also being increasingly identified.[1] In 2004, a syndrome with anatomical MPPH was described, with more and more clinical and radiological findings being added to describe this condition. Recently, we came across a 9-year-old boy with normal antenatal history and without history of consanguinity brought by the parents with complaints of global developmental delay, seizures, and autism spectrum disorder (ASD). His magnetic resonance imaging (MRI) brain and screening of spine were done, and findings were recorded [Figure 1a-h].Figure 1: (a and b) Arrows represent bilateral perisylvian polymicrogyria (BPP) (T2WI axial brain, T2WI coronal brain; respectively); (c and d) Arrows represent BPP and a small posterior fossa without Chiari malformation (T1WI inversion recovery coronal brain, T2WI sagittal spine; respectively); (e and f) Arrows represent normal cerebrovertebral junction and presence of thoracic cord syrinx (T2WI sagittal cervical spine, T2WI sagittal dorsolumbar spine; respectively); (g and h) Arrows represent long-segment syringomyelia involving the central part of cord (T2WI sagittal cervicodorsal spine, T2WI axial dorsal/thoracic spine; respectively)MRI revealed hydrocephalus, megalencephaly, bilateral perisylvian polymicrogyria (BPP) [Figure 1a-c], small posterior fossa, and syringomyelia without evidence of Chiari malformation [Figure 1d-h]. Though most of the MRI findings are described, the presence of syringomyelia without Chiari malformation is being reported for the first time. Furthermore, generalized small posterior fossa has not been reported, though hypoplasia of the brainstem has been reported earlier. MPPH is a relatively recently described disorder with 100 or less cases reported till date.[2] It presents with big size of head, polydactyly, developmental delay, autism, seizures, etc. There is absence of any cutaneous vascular malformations. Our patient had postaxial polydactyly and neurological manifestations. Apart from findings described in a classic case, note was made of unique MRI findings not described earlier. Isolated syringomyelia in the absence of Chiari malformation and small posterior fossa have not been reported, till date. Our case has long-segment syrinx involving the 5th–12th thoracic vertebral levels. The cerebrovertebral junction and cerebellar tonsils were unremarkable. Hence, it is the first case report in the world to show the presence of syringomyelia in the absence of Chiari malformation in a genetically proven (PIK3R2 gain of function mutation) case of MPPH syndrome, which itself is very rare (100 or less cases reported till now). Out of the two cases described to have syrinx,[2] one had germline AKT 3 mutation and associated type 1 Chiari malformation.[3] Another case had a CCND 2 variant. It had brainstem hypoplasia and cervical cord syrinx.[4] Till date, dorsal or thoracic cord long-segment syringomyelia has not been described in the absence of Chiari malformation,[5] that too, in a genetically proven case of PIK3R2 gain of function.[2,3] More and more research is required to explain the presence of syrinx in these cases. The mechanism to explain syrinx in a case of Chiari malformation may not hold true in MPPH syndrome, as in our case. It is also interesting to note whether our case can lead to a genetic basis of the development of syrinx. Colpocephaly in the absence of overt hydrocephalus has also been described in MPPH syndrome.[6] Our patient has a gain-of-function PIK3R2, which is strongly associated with BPP and the most common genetic cause of MPPH.[7] It encodes key proteins within the mammalian target of rapamycin pathway. This pathogenic gain-of-function variants in PIK3R2 occur in sporadic tumors, particularly endometrial cancer, in the absence of any other findings of MPPH syndrome.[8] The presence of this mutation with syringomyelia in the absence of Chiari malformation has not been described till date, and here, a report is made to this association, which adds to the scarce literature available about this rare condition.[8] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that the name and initials will not be published and due efforts will be made to conceal the patient identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
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