Megarbane et al. reported for the first time a consanguineous Lebanese family (Nair 2006). This family demonstrates the autosomal recessive inheritance of the disorder. The family had three affected children that all presented the same severe symptoms, however, the parents and other siblings had no signs of the disease. The first case involved an eight-year-old boy, whose hearing and walking impairment started at two years of age. Upon examining the boy, it was found that he was weak, completely deaf, and hypotonic. Neurological examination showed low muscle tone; dorsal scoliosis; tongue contractions; a small number of spontaneous movements; neck, shoulder and upper arm muscular weakness; clawed hands; absent deep tendon reflexes; and no Babinski response. Upon radiological examination, the patient showed left curved scoliosis and thin diaphyses of the long bones. The patient died at five, most likely due to respiratory failure. The patient’s younger brother suffered from the same disease, and demonstrated limited speech and vocalization by the age of seven. He also showed similar neurological symptoms as his brother, and died four months after the onset of symptoms. The third case in the immediate family was the two patients’ sister who died at the age of four with symptoms similar to her brothers. Finally, the patients had a cousin whose neurological features were identical to his cousins. All of these patients had symptoms indicative of BVVL. It is thought that identification of the gene responsible for the family’s disorder would be a major step in knowing the etiology of this disease (Nair 2006).
BVVL syndrome is often found in late childhood and adolescents, however, seven cases have been found with symptoms starting within the first five years (Voudris 2002).
The youngest case of BVVL was documented by Voudris (Voudris 2002). The patient was a male infant who had a normal birth and neonatal period, healthy parents and no family history of neurological disorders. This male was the youngest patient in literature who featured severe symptoms of BVVL syndrome. At twelve months, the patient developed an upper respiratory infection and demonstrated both stridor and harshness of voice. Three weeks later, the child showed apnea, suspension of external breathing, and was artificially ventilated for three days. However, aside from slight bilateral facial weakness the patient showed a relatively normal neurological examination with normal motor and sensory nerve conduction. At fourteen months, the child developed dysphagia, or difficulty swallowing, and was then fed with a catheter. Between fifteen and eighteen months, the patient showed progressive neurological degeneration with symptoms such as paralysis of extraocular muscles responsible for eye movements, bilateral facial palsy, weakness of jaw muscles and tongue, and sever weakness of upper extremities with disappearance of tendon reflexes. Between eighteen and twenty-one months, the child became lethargic and unresponsive, lost interchange between sleep and awakening, and no longer reacted to any visual or auditory stimulation. The patient died at twenty-one months of respiratory failure. This particular case of BVVL syndrome differs from others in that the patient had severe symptoms at an unusually early age. While no autopsy on the child was performed, researchers are hoping that the unusual symptoms in this case and other similar cases can be used to provide a link between BVVL syndrome and Fazio-Londe disease (Voudris 2002).
The syndrome can be fatal or protracted for a longer period. There are three documented cases of BVVL where the patient died within the first five years of the disease. On the contrary, at least fourteen patients have survived more than 10 years after the onset of their first symptom, and several cases have survived 20-30 years after the onset of their first symptom (Sathasivam 2000).
Families with multiple cases of BVVL and more generally, multiple cases of Infantile Progressive Bulbar Palsy, can show variability in age of disease onset and survival. Dipti and Childs described such a situation in which a family had five children that had Infantile PBP. In this family, three siblings showed sensorineural deafness and other symptoms of BVVL at an older age. The other two siblings showed symptoms of Fazio-Londe disease and died before the age of two (Dipti 2005).
The first report of BVVL syndrome in Japanese literature was of a woman that had BVVL and showed improvement after such treatments. The patient was a sixty-year-old woman that had symptoms such as sensorineural deafness, weakness, and atrophy since she was 15 years old. Around the age of 49 the patient was officially diagnosed with BVVL, intubated, and then attached to a respirator to improve her CO2 narcosis. After the treatments, the patient still required respiratory assistance during sleep; however, the patient no longer needed assistance by a respirator during the daytime (Hiroshi 2005).
Differential diagnosis of BVVL includes Boltshauser syndrome, Madras disease, progressive bulbar paralysis of Fazio Londe, Nathalie syndrome and ALS (Nair 2006)