Abstract
Malformations of the cerebral cortex are an important cause of developmental disabilities and epilepsy. Neurological disorders caused by abnormal neuronal migration have been observed to occur with mutations in tubulin genes. The α- and β-tubulin genes encode cytoskeletal proteins, which play a role in the developing brain. TUBA1A mutations are associated with a wide spectrum of neurological problems, which are characterized by peculiar clinical details and neuroradiologic patterns. This manuscript describes the case of a nine-year-old girl with microcephaly, mild facial dysmorphisms, epileptic seizures, and severe developmental delay, with a de novo heterozygous c.320A>G [p.(His 107 Arg)] mutation in TUBA1A gene, and the clinical aspects and neuroimaging features of “lissencephaly syndrome” are summarized. This case shows that TUBA1A mutations lead to a variety of brain malformations ranging from lissencephaly with perisylvian pachygyria to diffuse posteriorly predominant pachygyria, combined with internal capsule dysgenesis, cerebellar dysplasia, and callosal hypotrophy. This peculiar neuroradiological pattern, in combination with the usually severe clinical presentation, suggests the need for future molecular studies to address the mechanisms of TUBA1A mutation-induced neuropathology.
Highlights
The term malformation of cortical development describes a group of disorders that are associated with several neurologic problems, including neurodevelopment delay and epilepsy
According to the stage at which the neurodevelopmental process is disrupted, these disorders are divided into three groups: cases due to abnormal cell proliferation and apoptosis, those secondary to abnormal cell migration, and those that depend on abnormal postmigrational development [1]
Mutations of genes that are involved in neurogenesis, cell replication, and neuronal migration are associated with these clinical conditions
Summary
The term malformation of cortical development describes a group of disorders that are associated with several neurologic problems, including neurodevelopment delay and epilepsy. According to the stage at which the neurodevelopmental process is disrupted, these disorders are divided into three groups: cases due to abnormal cell proliferation and apoptosis, those secondary to abnormal cell migration, and those that depend on abnormal postmigrational development [1]. Mutations of genes that are involved in neurogenesis, cell replication, and neuronal migration are associated with these clinical conditions. LiMn.uMtautitoantisonins αin/αβ/-βtu-tbuubluinlingegneensesmmigihgthtalatletrerththeeddyynnaammicicfufunncctitoionnssooffmmicicrroottuubbuulleessaannddccaauussee aa wwiiddee ssppeeccttrruumm ooff cceerreebbrraall mmaallffoorrmmaattiioonnss,, iinncclluuddiinngg mmiiccrroocceepphhaallyy,, lliisssseenncceepphhaallyy,, ppaacchhyyggyyrriiaa,, bbaanndd hheetteerroottooppiiaa,, aabbnnoorrmmaall wwhhiittee mmaatttteerr ttrraaccttss aanndd ccrraanniiaall nneerrvveess,, aanndd mmaallffoorrmmaattiioonnss ooff tthhee mmiidd-- aanndd hhiinnddbbrraaiinn [[77]]. AAlltthhoouugghh eexxppeerriimmeennttaall aanndd cclliinniiccaall ddaattaa iinnddiiccaattee tthhee ccrriittiiccaall rroollee ooff mmiiccrroottuubbuulleess dduurriinngg nneeuurraall ddeevveellooppmmeenntt,,ththeererlealtaiotinosnhsihpibpetbweetweneethne tchlienicclailnpichaelnpohtyepneoatynpdethaenmd utthaetiomnsutianttiohnesgeinnesthinevgoelvneeds iinnvtohlevseydnitnhethsiessoyfntthhiesspisrootfetihnisispnroottepinreicsisneolyt pdreeficniseedly. FaonriftehsetaTtiUoBnAs.1FAogretnhee, cTaUseBAre1pAorgtesnhea, vcaesdeersecproibretsdhtahvaet adlethscoruibgehdctohratticaallthmoaulgfohrmcoarttiicoanl rmesaelfmorbmlinatgiocnlarsessiceaml blilsinsegnccleapsshiaclayl cliosuseldncbeephdaeltyecctoedulidnbaelldpeatteicetnetds winitahllmpauttiaetniotsnswoitfhthmisugtaetnioe,nsspoefcitfihciscgoemnbe,insapteiocinfiscocfofmeabtiunraetsiocnosulodf bfeeatiudreensticfioeudlddebpeeinddeinntgifioend tdheeppenardtiincuglaorngtehneeptiacratilctuerlaartiognentehtaict iasltperraestieonnt t[h8–a1t 0i]s. pCreosnesnetq[u8e–n1t0l]y., tChoendseesqcureipnttiloyn, tohfeaddedsictrioipntaiol npaotfieandtds iwtioitnhaml puatatiteionntsswinitthhemTuUtaBtiAo1nAs ignetnheeisTUesBseAn1tAialgteonbeeitsteerssdeenfitinael tthoebseptteecrtrduemfinoef pthheensopteycptreusmassoofcpiahteendowtyipthesTaUsBsoAc1iaAtemduwtaittihonT.UTBhAis1mAamnuustacrtiiopnt .pTrehsiesnmtsaanpuasctireipntt wpriethseandtse naopvaotiheentterwozityhgoausdTe UnBoAvo1Ahmetuertaotziyognoaunsd TsuUmBmA1aArizmesutthaeticolniniacnaldasspuemctms aanridzenseuthroeimclaingiicnagl faesapteucrtessaonfd“lnisesuernocimepahgailnygsfyenadturoremseo”f.“lissencephaly syndrome”
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