Answer for BIR CoW 06 Nov 2022
Tubulinopathy
Findings
Bilateral head of caudate nucleus and putamen are fused. Left thalamus is relatively larger than the right thalamus. Absent both anterior limb of internal capsules. The lateral ventricle are asymmetric. Dysmorphic brain stem with mild atrophy of right midbrain and reduced AP diameter of pons.
Discussion
Dysmorphism or unusual orientation of the basal ganglia (60/80; 75%) is one of the pathognomonic features of tubulinopathies. It is suspected to result from abnormal axon guidance of the corticospinal tract through the internal capsule This appearance is the result of a combination of a dysgenesis of the anterior limb of internal capsule with a head of the caudate protruding into the ventral horn of the ventricles. Consequently, the lateral ventricles are enlarged with a hooked aspect of the anterior horn. This is an easily recognizable feature on brain MRI and increasing awareness should steer clinicians and neuroradiologists in the direction of specific molecular genetic testing. Of note, the thalamus is usually less enlarged and this sign is particularly visible in association with cortical malformations of mild to moderate severity milder neurological phenotype and only highly localized areas of irregular cortex, described as ‘focal polymicrogyria There is also a high association with ventriculomegaly, corpus callosal agenesis (up to 40%), and cerebellar hypoplasia of varying degrees in these patients as well Tubulins play an important role in neuronal migration in the developing foetal brain Abnormalities of microtubules impair axon navigation and result in diminished size of nerves and white matter bundles, manifesting in patients with tubulin mutations as abnormalities of the corpus callosum, cranial nerves and internal capsule. majority of tubulinopathies result from de novo mutations, others such as TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB5 and TUBG1 are autosomal dominant in inheritance Five common cortical malformation patterns have been described in tubulinopathies: microlissencephaly agyria-pachygyria central pachygyria polymicrogyria-like cortical dysplasia simplified gyral pattern
References
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? Nadia Bahi-Buisson, Karine Poirier, Franck Fourniol, Yoann Saillour, Stéphanie Valence, Nicolas Lebrun, Marie Hully, Catherine Fallet Bianco, Nathalie Boddaert, Caroline Elie . Overlapping cortical malformations and mutations in TUBB2B and TUBA1A Thomas D. Cushion, William B. Dobyns, Jonathan G. L. Mullins, Neil Stoodley, Seo-Kyung Chung, Andrew E. Fry, Ute Hehr, Roxana Gunny, Arthur S. Aylsworth, Prab Prabhakar Complication begets clarification in classification James Barkovich A Pachygyria-causing α-Tubulin Mutation Results in Inefficient Cycling with CCT and a Deficient Interaction with TBCB Guoling Tian, Xiang-Peng Kong, Xavier H. Jaglin, Jamel Chelly, David Keays,Nicholas J. Cowan
Findings
Bilateral head of caudate nucleus and putamen are fused. Left thalamus is relatively larger than the right thalamus. Absent both anterior limb of internal capsules. The lateral ventricle are asymmetric. Dysmorphic brain stem with mild atrophy of right midbrain and reduced AP diameter of pons.
Discussion
Dysmorphism or unusual orientation of the basal ganglia (60/80; 75%) is one of the pathognomonic features of tubulinopathies. It is suspected to result from abnormal axon guidance of the corticospinal tract through the internal capsule This appearance is the result of a combination of a dysgenesis of the anterior limb of internal capsule with a head of the caudate protruding into the ventral horn of the ventricles. Consequently, the lateral ventricles are enlarged with a hooked aspect of the anterior horn. This is an easily recognizable feature on brain MRI and increasing awareness should steer clinicians and neuroradiologists in the direction of specific molecular genetic testing. Of note, the thalamus is usually less enlarged and this sign is particularly visible in association with cortical malformations of mild to moderate severity milder neurological phenotype and only highly localized areas of irregular cortex, described as ‘focal polymicrogyria There is also a high association with ventriculomegaly, corpus callosal agenesis (up to 40%), and cerebellar hypoplasia of varying degrees in these patients as well Tubulins play an important role in neuronal migration in the developing foetal brain Abnormalities of microtubules impair axon navigation and result in diminished size of nerves and white matter bundles, manifesting in patients with tubulin mutations as abnormalities of the corpus callosum, cranial nerves and internal capsule. majority of tubulinopathies result from de novo mutations, others such as TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB5 and TUBG1 are autosomal dominant in inheritance Five common cortical malformation patterns have been described in tubulinopathies: microlissencephaly agyria-pachygyria central pachygyria polymicrogyria-like cortical dysplasia simplified gyral pattern
References
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? Nadia Bahi-Buisson, Karine Poirier, Franck Fourniol, Yoann Saillour, Stéphanie Valence, Nicolas Lebrun, Marie Hully, Catherine Fallet Bianco, Nathalie Boddaert, Caroline Elie . Overlapping cortical malformations and mutations in TUBB2B and TUBA1A Thomas D. Cushion, William B. Dobyns, Jonathan G. L. Mullins, Neil Stoodley, Seo-Kyung Chung, Andrew E. Fry, Ute Hehr, Roxana Gunny, Arthur S. Aylsworth, Prab Prabhakar Complication begets clarification in classification James Barkovich A Pachygyria-causing α-Tubulin Mutation Results in Inefficient Cycling with CCT and a Deficient Interaction with TBCB Guoling Tian, Xiang-Peng Kong, Xavier H. Jaglin, Jamel Chelly, David Keays,Nicholas J. Cowan
Note:
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!