Pontobulbar Palsy and Neurosensory Deafness (Brown-Vialetto-van Laere Syndrome) With Hyperintense Brainstem Nuclei on Magnetic Resonance Imaging: New Finding in Three Siblings

Abstract

Three siblings (one boy and two girls) with Brown-Vialetto-van Laere syndrome are reported. A peculiar feature of onset with hearing loss in a patient with multiple cranial nerve palsies and a positive family history suggests this diagnosis. In our family, an autosomal recessive mode of inheritance was seen. In addition, we observed that early onset was associated with rapid deterioration and death. Optic nerve involvement and hyperintensity of the brainstem nuclei on magnetic resonance imaging (MRI) are two new features described in this report.

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2

“…This finding is in contrast to reports of hyperintensity of brainstem nuclei (Koul et al , 2006; Malheiros et al , 2007), atrophy of the brainstem (Francis et al , 1993; Koc et al , 2003; Malheiros et al , 2007) and atrophy of the cerebellum (Francis et al , 1993; Koc et al , 2003) in genetically undifferentiated cohorts of patients with Brown-Vialetto-Van Laere syndrome.…”

“…Early onset weakness in the upper limbs and neck is almost invariably seen in patients with mutations in SLC52A2 , in contrast to those patients with SLC52A3 mutations or genetically unclassified Brown-Vialetto-Van Laere syndrome, in whom the onset of weakness is often more generalized (Green et al , 2010; Bosch et al , 2011). Another distinctive feature of patients with SLC52A2 mutations is a lack of upper motor neuron signs in the lower limbs, a commonly reported clinical feature of Brown-Vialetto-Van Laere syndrome (Gallai et al , 1981; Hawkins et al , 1990; Francis et al , 1993; Voudris et al , 2002; De Grandis et al , 2005; Dipti et al , 2005; Koul et al , 2006) and, in particular, reported in patients with mutations in SLC52A3 (Green et al , 2010). Furthermore, the most common initial presenting symptom reported in case reports and reviews of Brown-Vialetto-Van Laere syndrome is bilateral hearing loss (Gallai et al , 1981; Sathasivam, 2008).…”

“…It is notable that normal nerve conduction velocities have been reported in patients diagnosed with Brown-Vialetto-Van Laere syndrome (Voudris et al , 2002; Dipti et al , 2005; Koul et al , 2006) and that sensory loss and abnormalities on sensory nerve conduction studies have not been commonly recognized as part of the phenotype of Brown-Vialetto-Van Laere syndrome in cohorts of genetically undifferentiated patients (Sathasivam, 2008). This is in stark contrast with our cohort of patients with mutations in SLC52A2 who presented with sensory ataxia and nerve conduction studies revealing an axonal sensorimotor neuropathy.…”

Brown-Vialetto-Van Laere syndrome

“…The female to male ratio is approximately 3:1 in reported cases. This may be the result of reporting bias as males tend to be more severely affected and therefore die earlier in life [ 5 - 10 ].…”

Brown–Vialetto–van Laere and Fazio–Londe overlap syndromes: A clinical, biochemical and genetic study

“…Optic nerve involvement and hyperintensity of the brainstem nuclei on brain MRI have been described in three siblings who were clinically diagnosed as BVVL syndrome [21]. However in our patients with genetically confirmed BVVL no neuroradiological abnormalities were observed, in spite of having neuroimaging in one patient during severe clinical status.…”