Abstract
Rationale: Mutations in the alpha-1a Tubulin (TUBA1A) gene have recently been described in patients with
malformations of cortical development ranging from perisylvian to posteriorly predominant pachygyria with
associated malformations of the corpus callosum and cerebellum.
Methods: MRI of the brain, EEG, cardiac and renal ultrasound, and X-ray of the spine were carried out.
MLPA analysis of LIS1, DCX, POMT1, POMGnT1, FLNA genes as well as sequencing of DCX and
TUBA1A genes were performed.
Results: The proband, a 18-month old boy, was born at term after an uneventful pregnancy. Head
circumference at birth was 31 cm. He presented with severe hypotonia and feeding difficulties, and
developed neonatal convulsions for which treatment with phenobarbital, phenytoin and valproate was
initiated. Early EEGs showed episodes of high voltage delta activity with diffuse irregular spikes, followed
by episodes of low voltage activity with very little variation. Seizures eventually were controlled by
vigabatrin, topiramate and phenobarbital. MRI of the brain showed frontoparietal agyria and less severe
pachygyria over the occipital and temporal lobes. The anterior limb of the internal capsule was small, the
corpus callosum was thin and there was severe ventriculomegaly. The sylvian fissure was verticalised.
There was mild hypoplasia of the inferior vermis and the medio-inferior aspect of the cerebellar lobes.
Cardiac and renal ultrasounds were normal. X-ray of the spine showed a spina bifida occulta at S2. MLPA
analysis revealed no duplicaton or deletion in the above mentioned genes. Mutation analysis of TUBA1A
showed that the patient was heterozygous for a novel missense mutation c.629A>G (p.Tyr210Cys). The
mutation was absent in both parents.
Conclusions: Patients with lissencephaly often present with neonatal seizures. Mutation analysis of
TUBA1A is indicated in patients with lissencephaly, especially in the presence of microcephaly and associated malformations including dysgenesis of the anterior limb of the interal capsule, thin corpus
callosum, and inferior vermis hypoplasia.
malformations of cortical development ranging from perisylvian to posteriorly predominant pachygyria with
associated malformations of the corpus callosum and cerebellum.
Methods: MRI of the brain, EEG, cardiac and renal ultrasound, and X-ray of the spine were carried out.
MLPA analysis of LIS1, DCX, POMT1, POMGnT1, FLNA genes as well as sequencing of DCX and
TUBA1A genes were performed.
Results: The proband, a 18-month old boy, was born at term after an uneventful pregnancy. Head
circumference at birth was 31 cm. He presented with severe hypotonia and feeding difficulties, and
developed neonatal convulsions for which treatment with phenobarbital, phenytoin and valproate was
initiated. Early EEGs showed episodes of high voltage delta activity with diffuse irregular spikes, followed
by episodes of low voltage activity with very little variation. Seizures eventually were controlled by
vigabatrin, topiramate and phenobarbital. MRI of the brain showed frontoparietal agyria and less severe
pachygyria over the occipital and temporal lobes. The anterior limb of the internal capsule was small, the
corpus callosum was thin and there was severe ventriculomegaly. The sylvian fissure was verticalised.
There was mild hypoplasia of the inferior vermis and the medio-inferior aspect of the cerebellar lobes.
Cardiac and renal ultrasounds were normal. X-ray of the spine showed a spina bifida occulta at S2. MLPA
analysis revealed no duplicaton or deletion in the above mentioned genes. Mutation analysis of TUBA1A
showed that the patient was heterozygous for a novel missense mutation c.629A>G (p.Tyr210Cys). The
mutation was absent in both parents.
Conclusions: Patients with lissencephaly often present with neonatal seizures. Mutation analysis of
TUBA1A is indicated in patients with lissencephaly, especially in the presence of microcephaly and associated malformations including dysgenesis of the anterior limb of the interal capsule, thin corpus
callosum, and inferior vermis hypoplasia.
| Original language | English |
|---|---|
| Pages (from-to) | 151-151 |
| Number of pages | 1 |
| Journal | Epilepsia |
| Volume | Suppl |
| Issue number | 50 |
| Publication status | Published - 6 Oct 2009 |
| Event | Finds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden Duration: 21 Sep 2009 → 25 Sep 2009 |
Keywords
- TUBA1A
- lissencephaly