Pontine tegmental cap dysplasia: report of two new cases from Kuwait.

We describe two patients (a Filipino boy aged 2.7 years and a Kuwaiti girl aged 4.8 Years) with clinical and MRI findings consistent with the diagnosis of pontine tegmental cap dysplasia (PTCD) and compare them with 23 other cases reported in the literature. Both presented with feeding problems (VII nerve), sensori-neural deafness (VIII nerve) and hypotonia from birth and later developed corneal opacities due to loss of corneal sensation (V nerve). They have severe psychomotor developmental delay. The MRI of their brain showed a flattened ventral pons, vaulted "cap"- like structure protruding into 4th ventricle and a "molar tooth" sign. One of our patients also had Tetralogy of Fallot (TOF) successfully corrected. The other had no extracranial manifestations. The findings in our patients are similar to those reported except for the occurrence of TOF which has not been reported before in association with PTCD.

Interpeduncular heterotopia in Joubert syndrome: a previously undescribed MR finding.

The so-called molar tooth sign is the radiologic hallmark of JSRD. Joubert syndrome is a rare, most often autosomal-recessive disorder with a characteristic malformation of the midhindbrain. We describe 3 patients with JSRD and the additional MR finding of tissue resembling heterotopia in the interpeduncular fossa, which in one patient was combined with a more extensive intramesencephalic heterotopia. Interpeduncular heterotopia has not been reported previously, either in the context of JSRD or as a separate entity. This new imaging feature enlarges the spectrum of brain stem abnormalities in JSRD. In view of the underlying ciliopathy, it seems likely that the interpeduncular heterotopia results from misdirected migration.

Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging.

OBJECTIVE: Biomarkers to monitor neurological dysfunction in Neuronopathic Gaucher disease (NGD) are lacking. Diffusion tensor imaging (DTI) is a technique which allows us to probe the microstructure of the white-matter of the brain, in-vivo. The aim of this study was to investigate the value of DTI to visualise and quantify white matter integrity in children with NGD and Type I Gaucher. DESIGN: DTI was performed and fractional anisotropy (FA), mean diffusivity (MD), axial (λ(axial)) diffusivity and radial (λ(radial)) diffusivity maps calculated. Tract-based spatial statistics (TBSS) was used to perform a voxel-wise statistical analysis of the main white matter structures compared to age-sex matched control groups. SETTING: The study was performed at Great Ormond Street Children's Hospital NHS Trust PATIENTS: Four NGD and three Type I Gaucher paediatric patients were recruited RESULTS: The findings suggest the presence of microstructural white matter changes in NGD patients primarily in the middle cerebellar peduncles compared to an age-sex matched control group. This finding is relevant to the clinical manifestation of ataxia seen in NGD. Diffuse non-specific changes were seen in the Type I patients, but without a focal point. CONCLUSIONS: This study is the first to use DTI to examine the Gaucher brain. While the numbers studied are small, the results suggest that DTI may be an attractive surrogate marker of NGD, worthy of further exploration for use in clinical studies.

Sim1 and Sim2 are required for the correct targeting of mammillary body axons.

The mammillary body (MB), and its axonal projections to the thalamus (mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract, MTEG), are components of a circuit involved in spatial learning. The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We have found that MB neurons are generated and that they survive at least until E18.5 in embryos lacking both Sim1 and Sim2 (Sim1(-/-);Sim2(-/-)). However, the MTT and MTEG are histologically absent in Sim1(-/-);Sim2(-/-) embryos, and are reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating a contribution of the latter to the development of MB axons. We have generated, by homologous recombination, a null allele of Sim1 (Sim1(tlz)) in which the tau-lacZ fusion gene was introduced, allowing the staining of MB axons. Consistent with the histological studies, lacZ staining showed that the MTT/MTEG is barely detectable in Sim1(tlz/tlz);Sim2(+/-) and Sim1(tlz/tlz);Sim2(-/-) brains. Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2, which code for secreted molecules that induce the repulsion of ROBO1-producing axons, are expressed in the midline at the level of the MB, whereas Robo1 is expressed in the developing MB. The expression of Rig-1/Robo3, a negative regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2 double mutants, raising the possibility that the growth of mutant MB axons towards the midline is caused by a decreased sensitivity to SLIT. Finally, we found that Sim1 and Sim2 act along compensatory, but not hierarchical, pathways, suggesting that they play similar roles in vivo.

Vermian agenesis and unsegmented midbrain tectum. Case report.

A male infant had spells of tachypnea leading to apnea. He had vermian agenesis and and unsegmented midbrain tectum. This identifies the time of teratogenesis at about embryonic stage XVII to XVII (40 days gestation).