OBJECTIVE To describe fetal, clinical, radiological, morphological features of TUBB3 related syndrome. METHODS We report two families each of two generations harboring a novel and a previously described heterozygous TUBB3 pathogenic variants. We compared these patients with other published TUBB3-related cases. We describe the pathological features of dysgyria in the two aborted fetuses. RESULTS The mother and son from family 1 had a history of mild developmental delay in motor and language skills and demonstrated mild cerebellar signs and mirror movements. Neuroimaging findings included: hypoplastic corpus callosum (CC), asymmetric ventriculomegaly and cerebellar vermis hypoplasia in all patients and frontal dysgyria in three. Autopsy of the fetal brain showed an unusual shape and orientation of the frontal sulci and gyri with normal cortical layering and no abnormal cell types. The mother of family 2 had congenital strabismus, mild muscle weakness on the right and a past history of developmental delay. Fetal brain MRI showed abnormal cerebral sulcation, hemispheric asymmetry, asymmetric ventriculomegaly, dysmorphic short CC and frontal cortical interdigitation. Autopsy demonstrated fronto-parietal predominant dysgyria, bilateral ventriculomegaly, hippocampal and CC hypoplasia, abnormal Sylvian fissure. Lamination and neuron morphology in the areas of dysgyria were normal. CONCLUSIONS TUBB3 related cortical malformations can be mild, consistent with dysgyria rather than typical pachygyria or polymicrogyria. The autopsy findings in fetal TUBB3 related dysgyria are abnormal orientation of sulci and gyri, but normal neuron morphology and layering. We suggest that TUBB3 - associated brain malformations can be suspected in-utero which in turn can aid in prognostic counselling and interpretation of genetic testing.

中文翻译：

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常染色体显性遗传 TUBB3 相关综合征：胎儿、放射学、临床和形态学特征

目的 描述 TUBB3 相关综合征的胎儿、临床、放射学、形态学特征。方法我们报告了两个家族，每一代都有一个新的和先前描述的杂合 TUBB3 致病变异。我们将这些患者与其他已发表的 TUBB3 相关病例进行了比较。我们描述了两个流产胎儿的旋转障碍的病理特征。结果 家庭 1 的母子有轻微的运动和语言发育迟缓病史，并表现出轻微的小脑体征和镜像运动。神经影像学发现包括：所有患者的胼胝体发育不全（CC）、不对称脑室扩大和小脑蚓部发育不全，以及三个患者的额叶回旋障碍。胎儿大脑的尸检显示额叶沟和脑回的形状和方向异常，皮质分层正常，没有异常细胞类型。家庭 2 的母亲有先天性斜视、右侧轻度肌无力和发育迟缓既往史。胎儿脑部MRI显示脑沟异常，半球不对称，不对称脑室扩大，畸形短CC和额叶皮质交错。尸检显示额顶叶为主的旋转障碍、双侧脑室扩大、海马和 CC 发育不全、侧裂异常。回旋障碍区域的分层和神经元形态正常。结论 与 TUBB3 相关的皮质畸形可能是轻微的，与旋转障碍一致，而不是典型的脑回或多小脑回。胎儿TUBB3相关的脑回旋障碍的尸检结果是脑沟和脑回方向异常，但神经元形态和分层正常。我们建议可以在子宫内怀疑与 TUBB3 相关的脑畸形，这反过来有助于预后咨询和基因检测的解释。