Ann Otol 88 :1979
BILATERAL ABDUCTOR VOCAL CORD PARALYSIS IN CHARCOT-MARIE-TOOTH DISEASE D. M. VUCKOVICH, MD PAUL H. HOLINGER, MDt
PAUL C. HOLINGER, MD LAUREN D. HOLINGER, MD
CmCAGO, ILLINOIS
This report describes the unusual association of bilateral abductor vocal cord paralysis (BAbVCP) and Charcot-Marie-Tooth disease in a boy and his natural mother who have been followed for eight years. The boy initially presented with life-threatening respiratory distress at age ten years; BAbVCP was documented by direct laryngoscopy. Mirror laryngoscopy confirmed BAbVCP in the mother. Neurological diagnosis was made by history, physical examination, electromyography, and nerve conduction velocity studies. The BAbVCP may represent an additional genetic marker within the spectrum of heredodegenerative disorders. Of clinical importance is examination of voice and respiratory symptomatology of patients with heredodegenerative diseases and neurological work-up of patients with familial vocal cord paralysis. Further genetic and clinical studies of X cranial nerve involvement in heredodegenerative disorders are warranted.
Charcot-Marie-Tooth disease (CMT), or peroneal muscular atrophy, has only rarely been associated with the clinical suggestion of involvement of the X cranial nerve.':" Although other cases of familial bilateral abductor vocal cord paralysis (BAbVCP) (X nerve dysfunction) have been described.v? some with characteristics of lower motor neuron involvement;' these reports lack a precise description of the neurological involvement which would permit a firm diagnosis of CMT or one of the related heredodegenerative ataxic disorders. This report of two patients with CMT and BAbVCP was prompted by a review of the etiology of bilateral laryngeal paralysis in 389 cases, 149 of whom were children." Of the 389 cases, two, a boy and his mother, were documented as familial and are reported here in detail. In addition to illustrating the lifethreatening nature of the respiratory problems, several theoretical and genetic issues are highlighted by these two patients. CASE REPORTS
LM. The patient, a white Jewish male, was initially admitted to The Children's Memorial Hospital, Chicago,
July 7, 1969, when he was 10-years old, for increasing stridor and respiratory distress. Past history disclosed that he had been the 3.15 kg product of a full term uncomplicated pregnancy and a normal spontaneous vaginal delivery. He had a weak cry and stridulous breathing at birth. Familv history revealed that the patient's father, paternal grandmother, and two paternal uncles were diabetic, and that his paternal grandfather died of a heart attack at age 45 years; the patient's younger brother was mentally retarded. Direct larvngosconv during the 1969 hosnitalization confirmed the presence of bilateral ahductor vocal cord paralysis. and a tracheotomy was necessarv. Neurological consultation disclosed bilateral pes cavus, greater on the left than right, diffusely depressed deep tendon reflexes (DTR ), partial left foot drop with shortening of the left Achilles tendon, no cranial nerve involvement other than X, no sensory loss, and normal intelligence. There was no evidence of cerebellar deficit, ataxia, tremors. involuntary movements or scoliosis. There was no acanthocvtosis, retinitis pigmentosa, or steatorrhea; serum lipids were
tDr. Paul H. Hollnger died March 26. 1978. From the Harvard University School of Public Health, Boston, Massachusetts and the Psychosmatlc and Psychiatric Institute, Michael Reese Hospital and Medical Center; the Division of Child Neurology, Loyola University Medical Center and the Division of Neurology, Columbus Hospital; and the Department of Bronchology, The Children's Memorial Hospital. Chicago. Illinois.
205
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normal. The patient was decannulated successfully and discharged August 1, 1969. In October, 1969, the patient was seen again for outpatient neurological evaluation. Truncal muscles were of good strength and superficial reflexes intact. The reflexes of the upper extremities were slightly hypoactive. Examination of the lower extremities confirmed significant depression of DTR bilaterally. There was wasting of the muscles of the left leg and to a lesser degree of the right. There was substantial weakness of the distal musculature of the left leg and foot, and a minimal weakness of the right foot. Sensory changes to pinprick were demonstrated on both legs, greater on the left than right. The nerve conduction velocity (NCV) and latency studies were normal (1969-1977); electromyography (EMG) showed evidence of fasciculation and fibrillation potentials (1969-1977).'" In the subsequent seven years the patient has been hospitalized four times for respiratory distress. He usually responded well to medical management, though he needed a second tracheotomy (with subsequent decannulations) in 1974. BAbVCP was confirmed during each admission: he and his family refused a corrective arytenoidectomy because it would entail a permanent voice deficit. There has been little change in subsequent neurological examinations, with the exception of finding a weakness of the right pterygoid muscle. PM (Natural Mother of Patient). PM, a Caucasian female, was noted by her son's physicians to have stridulous breathing of which she did not complain. Outpatient neurological examination was conducted in October 1969, when she was 48-years-old. Cranial nerve examination demonstrated only a weakness of the left pterygoid muscle in addition to involvement of the vocal cords. Superficial abdominal reflexes were depressed. DTR were absent in upper and lower extremities. Bilateral pes cavus was present. There was wasting of the lower extremities bilaterally,
greater distal to the knee than proximal. Weakness of the lower extremities was noted, more marked on the left than the right and more distal than proximal; the extensors of the feet were most severely affected. Sensory changes in the lower extremities consisted of pinprick impairment extending to midthigh. Upper extremities manifested only minimal weakness of the extensors of the wrist and abductors of the shoulders. There were no sensory changes demonstrated in the upper extremities. When fatigued, PM had slight hand tremors bilaterally. Her gait was wide-based with slight ataxia. She appeared to have poor circulation and unusual sensitivity to cold, more so in the upper than lower extremity. There was no acanthocytosis, retinitis pigmentosa, or steatorrhea; serum lipids were normal. Mirror examination of the larynx on December 28, 1970, disclosed BAbVCP with abduction insufficient to give her an uncompromised airway. NCV and latency studies showed prolongation in some nerves (1977); EMG demonstrated substantial fasciculation as well as fibrillation potentials (1977). PB (Natural Brother of Patient). The patient's younger brother was found to be mentally retarded. He was not available for further neurological or Iaryngological evaluation. DISCUSSION
The term BAbVCP is generally used to describe the loss of the abductor function of the laryngeal musculature. The relationship between the location of lesions to the nucleus ambiguus, the vagus or its laryngeal branches (superior and recurrent laryngeal nerves) and the resulting position of the vocal cords has remained unclear because no consistent pattern of laryngeal contour can be observed following such lesions;" recent research has been directed at clarification of these issues," With the single exception of the cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve, all intrinsic muscles of the larynx are
'EMG and NCV results for patients LM and PM are available upon request.
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
VOCAL CORD PARALYSIS IN CMT DISEASE
innervated by the recurrent laryngeal branch of the X cranial nerve. The posterior cricoarytenoid is the only abductor of the vocal cords; it is also innervated by the recurrent laryngeal nerve. Bilateral lesions of the recurrent laryngeal nerves leave the vocal cords flaccid in or near the midline (adduction). Since adduction is the position of phonation, the voice is essentially normal. However, due to their configuration the paralyzed vocal cords act as a one-way valve; this readily allows expiration and phonation but compromises inspiration to cause inspiratory stridor or, occasionally, even complete respiratory obstruction. This paradox of normal phonation and inspiratory stridor is characteristic of BAbVCP. In contrast, in unilateral vocal cord paralysis, while the involved cord is flaccid in or near the midline (adduction), there is no respiratory embarrassment because abduction of the uninvolved cord on inspiration creates an adequate airway; however, the voice is weak and breathy with an appreciable air loss on attempted phonation. Charot-Marie-Tooth disease is a hereditary disorder belonging to a broad spectrum of degenerative diseases including olivopontocerebellar, cerebelloparenchymal, and spinocerebellar disorders, and the neuropathies. CMT usually begins with weakness and atrophy of the peroneal muscles and may advance to include other distal muscles of the leg and arm; it is also characterized by diminished or absent deep tendon reflexes in the affected areas and pes cavus. Charcot and Marie's paper in 18861 0 and Tooth's study later in the same year'! are generally acknowledged to be the first comprehensive descriptions of the disease, although, as Dyck and Lambert'? note, patients with peroneal muscular atrophy had been described earlier. Despite the long history of CMT, several aspects of the pathology, etiology, genetics, and laboratory findings remain unresolved. Clinical variants, including features of the hereditary cerebellar ataxias, optic atrophy, deafness, and other cranial nerve involvement have been reported.P ?" Such reports, together with EMG, NCV,
207
enzyme, and genetic studies, have led to hypotheses about the existence of transitional forms between, and various classifications of, CMT and other heredodegenerative diseases of the nervous system.Y?" Possible involvement of the X cranial nerve in CMT has occasionally been reported.v" Aoyama" described a case of CMT disease with bulbar changes including the vagal nuclei and their fibers. Bensaid et al" observed persistent atrial standstill in two members of one family affected by a neuromuscular genetic disease of the Charcot-Marie type. Affliction of the conducting system was a suggested explanation for the atrial standstill, and the degree of possible involvement of the visceral efferent of the vagus nerve was unresolved. With respect to familial BAbVCP, Plott" described congenital laryngeal abductor nerve paralysis accompanied by mental deficiency in three male siblings, one of whom also had a left abducens nerve palsy. Watters and Fitch" studied three male infants (two brothers and the male cousin of their mother) with marked physical and mental retardation; all had laryngeal stridor in the newborn period and one had documented BAbVCP. Cacek' reported familial BAbVCP in a father and two sons. The father manifested round shoulders and some muscle loss about the upper limbs; the sons exhibited round shoulders, foot drop, and absence of DTR in the upper and lower extremities. Gacek also presented a second family, the unaffected sister of the father of the first family and her three sons. All three sons had abnormalities of the upper and lower limbs and two had evidence of abducens nerve paresis. No one in the second family had BAbVCP. Cacek' and Plott" both note that the question remains unresolved as to whether the mental deficiency is secondary to anoxia produced by BAbVCP or whether the mental deficiency and paralysis are coexisting congenital defects. This report presents two cases of CMT-type of heredodegenerative disease with documented BAbVCP, i.e., CMT with X nerve involvement. The
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
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issue of etiology of the vocal cord paralysis in these apparent hereditary cases remains unresolved, although several mechanisms and sites for the lesions have been proposed."? Also unresolved is the etiology of the mental retardation frequently seen in these patients.':" Lack of more widespread changes of NCV and latencies in these two cases is unusual in classical CMT (classified recently under hereditary and motor sensory neuropathy type I [HMSN type 1]).19 However, the absence of significant involvement of NCV in CMT has been described in the spinal form of the disease, HMSN type II, which may have a more benign clinical course." It is possible that a spectrum of involvement, from specific lesions in the brain stem to global central nervous system dysfunction (e.g., mental retardation), could occur within the framework of CMT, representing additional genetic markers. These markers could be closely situated to a gene locus for CMT or related disorders. Such a gene
locus was postulated by Yakura et apo who noted that their results with Marie's ataxia and HLA genotypes were understandable if they assumed the ataxia gene locus to be on the sixth human chromosome near the HLA loci. This suggestion by Yakura et al has been supported by Jackson et al." In conclusion, this review of two family members with CMT and BAbVCP demonstrates the importance of additional neurologic evaluation of the cranial nerves in the patient and family with CMT or other heredodegenerative disorders. It is particularly important to evaluate voice or respiratory symptomatology, which may represent involvement of the vagus. This involvement may be a significant genetic marker. Recognition of vocal cord paralysis in more than one family member may be a manifestation of a heredodegenerative disease; complete neurologic investigation including EMG and NCV studies may reveal the true nature of the underlying disorder.
REFERENCES 1. Bertolotti M: Etude clinique sur trois cas de maladie familiale degenerative du systeme nerveux, Nouv Iconographie Salpetriere: 23:97-134, 1911 2. Aoyama T: Ein Fall von neurotischer Muskelatrophie mit bulbaren Veranderungen. Dtsch Z NervenheiIkd 40:207-220, 1910 3. Bensaid J, Gilgenkrantz JM, Fernandez F, et al: Paralysie auriculaire permanente familiale en rapport probable avec une maladie genetlque du type Charcot-Marie. Arch Mal Coeur 65:935-952, 1972 4. Gacek RR: Hereditary abductor vocal cord paralysis. Ann Otol Rhinol Laryngol 85: 90-93, 1976 5. Plott D: Congenital laryngeal-abductor paralysis due to nucleus ambiguus dysgenesis in three brothers. N Engl J Med 271: 593-597, 1964 6. Watters GV, Fitch N: Familial laryngeal abductor paralysis and psychomotor retardation. Clin Genet 4:429-433, 1973 7. Holinger LD, Holinger PC, Holinger PH: Etiology of bilateral abductor vocal cord paralysis: A review of 389 vases. Ann Otol Rhinol Laryngol 85:428-436, 1976 8. Kirchner JA: Pressman and Kelemen's Physiology of the Larynx. Rochester, Minne-
sota, American Academy of Ophthalmology and Otolaryngology, 1970 9. Gacek RR, Malmgren LT, Lyon MJ: Localization of adductor and abductor motor nerve fibers to the larynx. Ann Otol Rhinol Laryngol 86:770-776, 1977 10. Charcot JM, Marie P: Sur une forme particuliere d'atrophie musculaire progressive souvent familial debutant par les pieds et les iambes et atteignant plus tard les mains. Rev Med (Paris) 6:97-138, 1886 11. Tooth HH: The Peroneal Type of Progressive Muscular Atrophy, thesis. London, HK Lewis & Co. Ltd., 1886 12. Dyck PI, Lambert EH: Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. I. Neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol 18:603618, 1968 13. Schwartz AR: Charcot-Marie-Tooth disease: a 45-year follow-up. Arch Neurol 9: 623-634, 1963 14. Dyck PJ, Lambert EH, Mulder DW: Charcot-Marie-Tooth disease: nerve conduction and clinical studies of a large kinship. Neurology 13:1-11, 1963 15. Kaeser HE: Scapuloperoneal muscular atrophy. Brain 88:407-418, 1965
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
VOCAL CORD PARALYSIS IN CMT DISEASE
16. Siegel 1M: Charcot-Marie-Tooth disease: A diagnostic problem. JAMA 228:873, 1974 17. Dyck PI, Lambert EH: Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. II. Neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol 18: 619-625, 1968 18. Rosenberg RN, Chutorian A: Familial opticoacoustic nerve degeneration and polyneuropathy. Neurol 17:827-832, 1967 REPRINTS -
209
19. Dyck PI, Thomas PK, Lambert EH: Peripheral Neuropathy Vol. II. Philadelphia, W. B. Saunders, 1975, pp 834-855 20. Yakura H, Wakisaka A, Fujimoto S, et al: Hereditary ataxia and HL-A genotypes, letter to editor. N Engl J Moo 291:154-155, 1974 21. Jackson JF, Currier RD, Terasaki P, et al: Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. N Engl J Med 296:1138-1141, 1977
Paul C. Holinger, MD, 1500 Lake Shore Drive, Chicago, IL 60610.
THE COPYRIGHT REVISION ACT OF 1976, EFFECTIVE JANUARY 1, 1978 In view of the Copyright Revision Act of 1976, effective January 1, 1978, all manuscripts sent to the ANNALS OF OTOLOGY, RHINOLOGY & LARYNGOLOGY must be accompanied by a letter containing the following language before manuscripts can be reviewed for possible publication: "The author ( s) undersigned hereby transfers, assigns or otherwise conveys all copyright ownership to the ANNALS PUBLISHING COMPANY in consideration of the ANNALS taking action in reviewing and editing my (our) manuscript and in the event that such work is published by the ANNALS."
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
BILATERAL ABDUCTOR VOCAL CORD PARALYSIS IN CHARCOT-MARIE-TOOTH DISEASE D. M. VUCKOVICH, MD PAUL H. HOLINGER, MDt
PAUL C. HOLINGER, MD LAUREN D. HOLINGER, MD
CmCAGO, ILLINOIS
This report describes the unusual association of bilateral abductor vocal cord paralysis (BAbVCP) and Charcot-Marie-Tooth disease in a boy and his natural mother who have been followed for eight years. The boy initially presented with life-threatening respiratory distress at age ten years; BAbVCP was documented by direct laryngoscopy. Mirror laryngoscopy confirmed BAbVCP in the mother. Neurological diagnosis was made by history, physical examination, electromyography, and nerve conduction velocity studies. The BAbVCP may represent an additional genetic marker within the spectrum of heredodegenerative disorders. Of clinical importance is examination of voice and respiratory symptomatology of patients with heredodegenerative diseases and neurological work-up of patients with familial vocal cord paralysis. Further genetic and clinical studies of X cranial nerve involvement in heredodegenerative disorders are warranted.
Charcot-Marie-Tooth disease (CMT), or peroneal muscular atrophy, has only rarely been associated with the clinical suggestion of involvement of the X cranial nerve.':" Although other cases of familial bilateral abductor vocal cord paralysis (BAbVCP) (X nerve dysfunction) have been described.v? some with characteristics of lower motor neuron involvement;' these reports lack a precise description of the neurological involvement which would permit a firm diagnosis of CMT or one of the related heredodegenerative ataxic disorders. This report of two patients with CMT and BAbVCP was prompted by a review of the etiology of bilateral laryngeal paralysis in 389 cases, 149 of whom were children." Of the 389 cases, two, a boy and his mother, were documented as familial and are reported here in detail. In addition to illustrating the lifethreatening nature of the respiratory problems, several theoretical and genetic issues are highlighted by these two patients. CASE REPORTS
LM. The patient, a white Jewish male, was initially admitted to The Children's Memorial Hospital, Chicago,
July 7, 1969, when he was 10-years old, for increasing stridor and respiratory distress. Past history disclosed that he had been the 3.15 kg product of a full term uncomplicated pregnancy and a normal spontaneous vaginal delivery. He had a weak cry and stridulous breathing at birth. Familv history revealed that the patient's father, paternal grandmother, and two paternal uncles were diabetic, and that his paternal grandfather died of a heart attack at age 45 years; the patient's younger brother was mentally retarded. Direct larvngosconv during the 1969 hosnitalization confirmed the presence of bilateral ahductor vocal cord paralysis. and a tracheotomy was necessarv. Neurological consultation disclosed bilateral pes cavus, greater on the left than right, diffusely depressed deep tendon reflexes (DTR ), partial left foot drop with shortening of the left Achilles tendon, no cranial nerve involvement other than X, no sensory loss, and normal intelligence. There was no evidence of cerebellar deficit, ataxia, tremors. involuntary movements or scoliosis. There was no acanthocvtosis, retinitis pigmentosa, or steatorrhea; serum lipids were
tDr. Paul H. Hollnger died March 26. 1978. From the Harvard University School of Public Health, Boston, Massachusetts and the Psychosmatlc and Psychiatric Institute, Michael Reese Hospital and Medical Center; the Division of Child Neurology, Loyola University Medical Center and the Division of Neurology, Columbus Hospital; and the Department of Bronchology, The Children's Memorial Hospital. Chicago. Illinois.
205
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
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normal. The patient was decannulated successfully and discharged August 1, 1969. In October, 1969, the patient was seen again for outpatient neurological evaluation. Truncal muscles were of good strength and superficial reflexes intact. The reflexes of the upper extremities were slightly hypoactive. Examination of the lower extremities confirmed significant depression of DTR bilaterally. There was wasting of the muscles of the left leg and to a lesser degree of the right. There was substantial weakness of the distal musculature of the left leg and foot, and a minimal weakness of the right foot. Sensory changes to pinprick were demonstrated on both legs, greater on the left than right. The nerve conduction velocity (NCV) and latency studies were normal (1969-1977); electromyography (EMG) showed evidence of fasciculation and fibrillation potentials (1969-1977).'" In the subsequent seven years the patient has been hospitalized four times for respiratory distress. He usually responded well to medical management, though he needed a second tracheotomy (with subsequent decannulations) in 1974. BAbVCP was confirmed during each admission: he and his family refused a corrective arytenoidectomy because it would entail a permanent voice deficit. There has been little change in subsequent neurological examinations, with the exception of finding a weakness of the right pterygoid muscle. PM (Natural Mother of Patient). PM, a Caucasian female, was noted by her son's physicians to have stridulous breathing of which she did not complain. Outpatient neurological examination was conducted in October 1969, when she was 48-years-old. Cranial nerve examination demonstrated only a weakness of the left pterygoid muscle in addition to involvement of the vocal cords. Superficial abdominal reflexes were depressed. DTR were absent in upper and lower extremities. Bilateral pes cavus was present. There was wasting of the lower extremities bilaterally,
greater distal to the knee than proximal. Weakness of the lower extremities was noted, more marked on the left than the right and more distal than proximal; the extensors of the feet were most severely affected. Sensory changes in the lower extremities consisted of pinprick impairment extending to midthigh. Upper extremities manifested only minimal weakness of the extensors of the wrist and abductors of the shoulders. There were no sensory changes demonstrated in the upper extremities. When fatigued, PM had slight hand tremors bilaterally. Her gait was wide-based with slight ataxia. She appeared to have poor circulation and unusual sensitivity to cold, more so in the upper than lower extremity. There was no acanthocytosis, retinitis pigmentosa, or steatorrhea; serum lipids were normal. Mirror examination of the larynx on December 28, 1970, disclosed BAbVCP with abduction insufficient to give her an uncompromised airway. NCV and latency studies showed prolongation in some nerves (1977); EMG demonstrated substantial fasciculation as well as fibrillation potentials (1977). PB (Natural Brother of Patient). The patient's younger brother was found to be mentally retarded. He was not available for further neurological or Iaryngological evaluation. DISCUSSION
The term BAbVCP is generally used to describe the loss of the abductor function of the laryngeal musculature. The relationship between the location of lesions to the nucleus ambiguus, the vagus or its laryngeal branches (superior and recurrent laryngeal nerves) and the resulting position of the vocal cords has remained unclear because no consistent pattern of laryngeal contour can be observed following such lesions;" recent research has been directed at clarification of these issues," With the single exception of the cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve, all intrinsic muscles of the larynx are
'EMG and NCV results for patients LM and PM are available upon request.
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
VOCAL CORD PARALYSIS IN CMT DISEASE
innervated by the recurrent laryngeal branch of the X cranial nerve. The posterior cricoarytenoid is the only abductor of the vocal cords; it is also innervated by the recurrent laryngeal nerve. Bilateral lesions of the recurrent laryngeal nerves leave the vocal cords flaccid in or near the midline (adduction). Since adduction is the position of phonation, the voice is essentially normal. However, due to their configuration the paralyzed vocal cords act as a one-way valve; this readily allows expiration and phonation but compromises inspiration to cause inspiratory stridor or, occasionally, even complete respiratory obstruction. This paradox of normal phonation and inspiratory stridor is characteristic of BAbVCP. In contrast, in unilateral vocal cord paralysis, while the involved cord is flaccid in or near the midline (adduction), there is no respiratory embarrassment because abduction of the uninvolved cord on inspiration creates an adequate airway; however, the voice is weak and breathy with an appreciable air loss on attempted phonation. Charot-Marie-Tooth disease is a hereditary disorder belonging to a broad spectrum of degenerative diseases including olivopontocerebellar, cerebelloparenchymal, and spinocerebellar disorders, and the neuropathies. CMT usually begins with weakness and atrophy of the peroneal muscles and may advance to include other distal muscles of the leg and arm; it is also characterized by diminished or absent deep tendon reflexes in the affected areas and pes cavus. Charcot and Marie's paper in 18861 0 and Tooth's study later in the same year'! are generally acknowledged to be the first comprehensive descriptions of the disease, although, as Dyck and Lambert'? note, patients with peroneal muscular atrophy had been described earlier. Despite the long history of CMT, several aspects of the pathology, etiology, genetics, and laboratory findings remain unresolved. Clinical variants, including features of the hereditary cerebellar ataxias, optic atrophy, deafness, and other cranial nerve involvement have been reported.P ?" Such reports, together with EMG, NCV,
207
enzyme, and genetic studies, have led to hypotheses about the existence of transitional forms between, and various classifications of, CMT and other heredodegenerative diseases of the nervous system.Y?" Possible involvement of the X cranial nerve in CMT has occasionally been reported.v" Aoyama" described a case of CMT disease with bulbar changes including the vagal nuclei and their fibers. Bensaid et al" observed persistent atrial standstill in two members of one family affected by a neuromuscular genetic disease of the Charcot-Marie type. Affliction of the conducting system was a suggested explanation for the atrial standstill, and the degree of possible involvement of the visceral efferent of the vagus nerve was unresolved. With respect to familial BAbVCP, Plott" described congenital laryngeal abductor nerve paralysis accompanied by mental deficiency in three male siblings, one of whom also had a left abducens nerve palsy. Watters and Fitch" studied three male infants (two brothers and the male cousin of their mother) with marked physical and mental retardation; all had laryngeal stridor in the newborn period and one had documented BAbVCP. Cacek' reported familial BAbVCP in a father and two sons. The father manifested round shoulders and some muscle loss about the upper limbs; the sons exhibited round shoulders, foot drop, and absence of DTR in the upper and lower extremities. Gacek also presented a second family, the unaffected sister of the father of the first family and her three sons. All three sons had abnormalities of the upper and lower limbs and two had evidence of abducens nerve paresis. No one in the second family had BAbVCP. Cacek' and Plott" both note that the question remains unresolved as to whether the mental deficiency is secondary to anoxia produced by BAbVCP or whether the mental deficiency and paralysis are coexisting congenital defects. This report presents two cases of CMT-type of heredodegenerative disease with documented BAbVCP, i.e., CMT with X nerve involvement. The
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
208
HOLINGER ET AL
issue of etiology of the vocal cord paralysis in these apparent hereditary cases remains unresolved, although several mechanisms and sites for the lesions have been proposed."? Also unresolved is the etiology of the mental retardation frequently seen in these patients.':" Lack of more widespread changes of NCV and latencies in these two cases is unusual in classical CMT (classified recently under hereditary and motor sensory neuropathy type I [HMSN type 1]).19 However, the absence of significant involvement of NCV in CMT has been described in the spinal form of the disease, HMSN type II, which may have a more benign clinical course." It is possible that a spectrum of involvement, from specific lesions in the brain stem to global central nervous system dysfunction (e.g., mental retardation), could occur within the framework of CMT, representing additional genetic markers. These markers could be closely situated to a gene locus for CMT or related disorders. Such a gene
locus was postulated by Yakura et apo who noted that their results with Marie's ataxia and HLA genotypes were understandable if they assumed the ataxia gene locus to be on the sixth human chromosome near the HLA loci. This suggestion by Yakura et al has been supported by Jackson et al." In conclusion, this review of two family members with CMT and BAbVCP demonstrates the importance of additional neurologic evaluation of the cranial nerves in the patient and family with CMT or other heredodegenerative disorders. It is particularly important to evaluate voice or respiratory symptomatology, which may represent involvement of the vagus. This involvement may be a significant genetic marker. Recognition of vocal cord paralysis in more than one family member may be a manifestation of a heredodegenerative disease; complete neurologic investigation including EMG and NCV studies may reveal the true nature of the underlying disorder.
REFERENCES 1. Bertolotti M: Etude clinique sur trois cas de maladie familiale degenerative du systeme nerveux, Nouv Iconographie Salpetriere: 23:97-134, 1911 2. Aoyama T: Ein Fall von neurotischer Muskelatrophie mit bulbaren Veranderungen. Dtsch Z NervenheiIkd 40:207-220, 1910 3. Bensaid J, Gilgenkrantz JM, Fernandez F, et al: Paralysie auriculaire permanente familiale en rapport probable avec une maladie genetlque du type Charcot-Marie. Arch Mal Coeur 65:935-952, 1972 4. Gacek RR: Hereditary abductor vocal cord paralysis. Ann Otol Rhinol Laryngol 85: 90-93, 1976 5. Plott D: Congenital laryngeal-abductor paralysis due to nucleus ambiguus dysgenesis in three brothers. N Engl J Med 271: 593-597, 1964 6. Watters GV, Fitch N: Familial laryngeal abductor paralysis and psychomotor retardation. Clin Genet 4:429-433, 1973 7. Holinger LD, Holinger PC, Holinger PH: Etiology of bilateral abductor vocal cord paralysis: A review of 389 vases. Ann Otol Rhinol Laryngol 85:428-436, 1976 8. Kirchner JA: Pressman and Kelemen's Physiology of the Larynx. Rochester, Minne-
sota, American Academy of Ophthalmology and Otolaryngology, 1970 9. Gacek RR, Malmgren LT, Lyon MJ: Localization of adductor and abductor motor nerve fibers to the larynx. Ann Otol Rhinol Laryngol 86:770-776, 1977 10. Charcot JM, Marie P: Sur une forme particuliere d'atrophie musculaire progressive souvent familial debutant par les pieds et les iambes et atteignant plus tard les mains. Rev Med (Paris) 6:97-138, 1886 11. Tooth HH: The Peroneal Type of Progressive Muscular Atrophy, thesis. London, HK Lewis & Co. Ltd., 1886 12. Dyck PI, Lambert EH: Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. I. Neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol 18:603618, 1968 13. Schwartz AR: Charcot-Marie-Tooth disease: a 45-year follow-up. Arch Neurol 9: 623-634, 1963 14. Dyck PJ, Lambert EH, Mulder DW: Charcot-Marie-Tooth disease: nerve conduction and clinical studies of a large kinship. Neurology 13:1-11, 1963 15. Kaeser HE: Scapuloperoneal muscular atrophy. Brain 88:407-418, 1965
Downloaded from aor.sagepub.com at Purdue University Libraries on July 17, 2015
VOCAL CORD PARALYSIS IN CMT DISEASE
16. Siegel 1M: Charcot-Marie-Tooth disease: A diagnostic problem. JAMA 228:873, 1974 17. Dyck PI, Lambert EH: Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. II. Neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol 18: 619-625, 1968 18. Rosenberg RN, Chutorian A: Familial opticoacoustic nerve degeneration and polyneuropathy. Neurol 17:827-832, 1967 REPRINTS -
209
19. Dyck PI, Thomas PK, Lambert EH: Peripheral Neuropathy Vol. II. Philadelphia, W. B. Saunders, 1975, pp 834-855 20. Yakura H, Wakisaka A, Fujimoto S, et al: Hereditary ataxia and HL-A genotypes, letter to editor. N Engl J Moo 291:154-155, 1974 21. Jackson JF, Currier RD, Terasaki P, et al: Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. N Engl J Med 296:1138-1141, 1977
Paul C. Holinger, MD, 1500 Lake Shore Drive, Chicago, IL 60610.
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