Infantile progressive bulbar palsy
Encyclopedia
Infantile Progressive Bulbar palsy is a rare type of progressive bulbar palsy
that occurs in children. The disease exists in both rapid and slow onsets, and involves inflammation of the gray matter of the bulb (Wilson 1909). Infantile PBP is a disease that manifests itself in two forms: Fazio Londe syndrome
(FL) and Brown-Vialetto-Van-Laere syndrome (BVVL).
, spinal motor nerves, and upper motor neurons (Voudris 2002).
(Prahbu 2005). However, several cases of BVVL have suggested that the syndrome may be autosomal dominant or X linked (Sathasivam 2000).
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).
To date, there is no test of confirmation for BVVL, although as of 2008, BVVL researchers are searching to isolate the responsible gene(s) for both BVVL and Fazio-Londe syndromes, as it has been proposed that Fazio-Londe disease and Brown-Vialetto-Van-Laere syndrome are a phenotypically associated condition. Visit http://www.bvvlinternational.org for more information.
of the tongue, and neurological disorders from the cranial nerves (Prahbu 2005). Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts
(Prahbu 2005). The first symptoms in nearly all cases of BVVL is progressive deafness, and the first initial symptoms are seen anywhere from one to three years (Sathasivam 2000). Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia
, retinitis pigmentosa
, epilepsy
, mental retardation
, and autonomic dysfunction (Sathasivam 2000). Non- neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness
, and hypertension
.
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 reflex
es. 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).
feeding and assisted ventilation
, while steroids may or may not help patients (Sathasivam 2000).
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)
Progressive bulbar palsy
Progressive bulbar palsy is a medical condition. It belongs to a group of disorders known as motor neuron diseases . PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex, spinal cord,...
that occurs in children. The disease exists in both rapid and slow onsets, and involves inflammation of the gray matter of the bulb (Wilson 1909). Infantile PBP is a disease that manifests itself in two forms: Fazio Londe syndrome
Fazio Londe syndrome
Fazio-Londe disease, also called progressive bulbar palsy of childhood, is an inherited motor neuron disease found in children and young adults.Progressive bulbar palsy is characterized by progressive paralysis of muscles innervated by cranial nerves....
(FL) and Brown-Vialetto-Van-Laere syndrome (BVVL).
Brown-Vialetto-Van-Laere syndrome (pontobulbar palsy with deafness)
Brown-Vialetto-Van-Laere syndrome (BVVL) is a rare degenerative disorder that is characterized by progressive sensorineural deafness (Voudris 2002). BVVL is marked by a number of cranial nerve palsies including those of the motor components involving the 7th and 9th-12th cranial nervesCranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
, spinal motor nerves, and upper motor neurons (Voudris 2002).
Origin
A sporadic case of BVVL was first classified by the late 19th century American physician C.H. Brown in 1894. The disease was further studied by 20th century Italian physician E. Vialetto in 1936, and then by 20th century Belgian physician Van Laere in 1966 (Sathasivam 2000).Epidemiology
Worldwide, there are thirty-eight known cases of Brown-Vialetto-Van-Laere syndrome (Voudris 2002). BVVL was first described in a Portuguese family, and has since been described in a number of ethnic groups. Reports have shown that BVVL infects females more than males at a rate of 5:1 respectively. However, males usually exhibit more severe symptoms, an earlier onset of deafness and a tendency to die earlier in life (Voudris 2002).Etiology
The etiology of BVVL is unknown (Prahbu 2005). Since about half of the 38 BVVL patients have no recognized symptoms in parents or relatives, it is thought that BVVL might be of autosomal recessive inheritanceDominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...
(Prahbu 2005). However, several cases of BVVL have suggested that the syndrome may be autosomal dominant or X linked (Sathasivam 2000).
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
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
. Neurological examination showed low muscle tone; dorsal scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
; 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).
To date, there is no test of confirmation for BVVL, although as of 2008, BVVL researchers are searching to isolate the responsible gene(s) for both BVVL and Fazio-Londe syndromes, as it has been proposed that Fazio-Londe disease and Brown-Vialetto-Van-Laere syndrome are a phenotypically associated condition. Visit http://www.bvvlinternational.org for more information.
Symptoms
Major features of BVVL include facial and neck weakness, fasciculationFasciculation
A fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
of the tongue, and neurological disorders from the cranial nerves (Prahbu 2005). Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts
Corticospinal tract
The corticospinal or pyramidal tract is a collection of axons that travel between the cerebral cortex of the brain and the spinal cord....
(Prahbu 2005). The first symptoms in nearly all cases of BVVL is progressive deafness, and the first initial symptoms are seen anywhere from one to three years (Sathasivam 2000). Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia
Cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum.-References:...
, retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, and autonomic dysfunction (Sathasivam 2000). Non- neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness
Color blindness
Color blindness or color vision deficiency is the inability or decreased ability to see color, or perceive color differences, under lighting conditions when color vision is not normally impaired...
, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Prognosis
The clinical course of BVVL can vary from one patient to another. There have been cases with progressive deterioration, deterioration followed by periods of stabilization, and deterioration with abrupt periods of increasing severity (Prahbu 2005).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
Stridor
Stridor is a high pitched wheezing sound resulting from turbulent air flow in the upper airway. Stridor is a physical sign which is produced by narrow or obstructed airway path. It can be inspiratory, expiratory or biphasic . Inspiratory stridor is common...
and harshness of voice. Three weeks later, the child showed apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
, 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
Nerve conduction study
A nerve conduction study is a test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body.Nerve conduction velocity is a common measurement made during this test...
. At fourteen months, the child developed dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their 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
Extraocular muscles
The extraocular muscles are the six muscles that control the movements of the eye . The actions of the extraocular muscles depend on the position of the eye at the time of muscle contraction.-List of muscles:-Importance:...
responsible for eye movements, bilateral facial palsy, weakness of jaw muscles and tongue, and sever weakness of upper extremities with disappearance of tendon reflex
Tendon reflex
Tendon reflex may refer to:*A stretch reflex, when the stretch is created by a blow upon a muscle tendon. This is the usual definition of the term...
es. 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).
Treatment
Patients with BVVL need symptomatic treatment and supportive care. This could include gastrostomyGastrostomy
Gastrostomy refers to a surgical opening into the stomach. Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression....
feeding and assisted ventilation
Ventilation (physiology)
In respiratory physiology, ventilation is the rate at which gas enters or leaves the lung. It is categorized under the following definitions:-Sample values:...
, while steroids may or may not help patients (Sathasivam 2000).
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
Narcosis
Narcosis may refer to:* Narcosis, the unconsciousness induced by a narcotic drug* Nitrogen narcosis, an effect of diving deep with nitrogen* Hydrogen narcosis, an effect of diving deep with hydrogenIn music:* Narcosis , an English metal band...
. 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)