Pontobulbar palsy and neurosensory deafness (Brown-Vialetto-Van Laere syndrome) with possible autosomal dominant inheritance.

Abstract

A female with the Brown-Vialetto-Van Laere syndrome is described. The patient's father, a paternal uncle, and possibly a paternal first cousin had neurosensory deafness and a paternal aunt had clinical symptoms indicative of the syndrome. This family raises the possibility that the. disorder is genetically heterogeneous with autosomal recessive and autosomal dominant forms. Alternatively, it could be caused by a mutant gene on the X chromosome.The Brown-Vialetto-Van Laere syndrome is a rare condition characterised by bilateral nerve deafness accompanied by cranial nerve disorders, usually involving the motor components of the seventh, and ninth to twelfth nerves.'5 In some cases, there is involvement of the spinal motor nerves and less commonly of upper motor neurones. The onset of the disease is usually in childhood. Although most reported cases are sporadic,' 3-`1 0 familial cases have been described.2 3 11 12The present paper describes an affected girl whose father and a paternal uncle had bilateral neurosensory deafness, and whose paternal aunt had bilateral neurosensory deafness and muscle weakness. It is suggested in this family that inheritance may be autosomal dominant or, alternatively, X linked. Case report The proband was born at term after a normal delivery. There was no history of adverse factors during the antenatal period. Development was normal. She was a healthy, athletic young girl who was a good swimmer with no neuromuscular problems before the onset of her illness. At the age of 12 years, over the course of a few weeks, she experienced rapid onset neurosensory deafness. The following year she developed rapidly progressive weakness with clumsiness of her upper limbs and difficulty in washing, dressing, writing, and combing her hair. At that time her mother noted she tended to shake and twitch particular at night. During the day she was sleepy. She also complained of shortness of breath. It was also noticed that she was unable to rise from lying, her speech was soft, and she had difficulty with swallowing.When aged 131/2 years, she was treated with steroids for 12 months, during which time her condition improved. When she was 15 years old she began to deteriorate again. On clinical examination of the cranial nerves the fields of vision were full and the pupillary responses were normal. The optic discs were pale but the optic fundi were normal. Visual acuity was normal. The external ocular movements were full. There was no ptosis. There was unsustained nystagmus on lateral gaze. The corneal responses were present. The jaw jerk was not obtained. There was weakness of the orbicularis oculi but muscles around the mouth had normal power. There was severe neurosensory deafness. The gag reflex was normal. The sternomastoid muscles were weak. The tongue was was small, wasted, and fasciculating.There was marked wasting of the muscles of the hands and forearms, more severe distally (MRC grade 2) than proximally (MRC grade 3/4). Power in the legs was grade 4-proximally and normal distally. The ten...

A Brazilian family with Brown-Vialetto-van Laere syndrome with autosomal recessive inheritance

“…Several types of inheritance have been described in BVVL: autosomal dominant or an alternative X linked 23,24 autosomal recessive 15 , besides sporadic cases and even from autoimmune origin 25,26 . The cases described in Brazil were all sporadic 9,10 , and the present series is the first with a clear autosomal recessive inheritance: the pedigree showing two generations of consanguineous marriages in witch all affected were females, strongly suggests this hypothesis.…”

Four novel C20orf54 mutations identified in Brown–Vialetto–Van Laere syndrome patients

“…20 Even possible autosomal dominant inheritance of BVVLS has been described in a few families. 18,19,22,23 The possibility that a single mutated allele in a gene can be cause of disease when usually two mutated alleles are causative has been considered for some neurologic disorders, such as for Parkinson's disease with respect to PARKN and for some myopathies such as limb-girdle muscular dystrophy with respect to TTN. [24][25][26][27] The case of SOD1 mutations with respect to amyotrophic lateral sclerosis, which like BVVLS is a motor neuron disorder, is also interesting.…”

“…Variable expressivity and incomplete penetrance with respect to BVVLS have been discussed in the past because some relatives of BVVLS-affected individuals were observed who presented with only some of the clinical features of BVVLS. [18][19][20][21] In some families, mildly affected patients were diagnosed only after more severely affected sibs had been identified. 20 Even possible autosomal dominant inheritance of BVVLS has been described in a few families.…”

Auditory neuropathy spectrum disorder with Brown–Vialetto–Van Laere syndrome: challenges in hearing rehabilitation

“…1 Most familial cases have an autosomal recessive inheritance pattern, with a few cases showing autosomal dominant or X-linked inheritance. [4][5][6] Sensorineural hearing loss is a common presenting symptom, although the disease can also present with subtle neurological features such as limb weakness and slurred speech. The disease course is unpredictable, with death occurring in 40 per cent of cases within 5 years of onset; however, a similar percentage of patients survive for more than 10 years after onset of the first symptom.…”