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Hypotonia, congenital nystagmus, and abnormal auditory brainstem response
Hypotonia, Congenital Nystagmus, and Abnormal Auditory Brainstem Response Pen-Jung Wang, MD, R o n g - L o n g C h e n , M D , and Y u - Z e n Shen, M D
A Taiwanese boy, 1 year, 8 months of age, is reported with poor weight gain, hypotonia, trunk ataxia, motor developmental retardation, and horizontal pendular nystagmus with only wave I on auditory brainstem responses. Our patient clinically resembled 9 patients reported in the Japanese literature. Because of its male predominance, occurrence in siblings, early onset, nonprogressive course, and characteristic auditory brainstem response findings, the syndrome may be of genetic origin and attributable to a dysgenetic brainstem lesion. Wang P-J, Chen R-L, Shen Y-Z. Hypotonia, congenital nystagmus, and abnormal auditory brainstem response. Pediatr Neurol 1989;5:381-3.
retardation, or other relevant diseases. He was born at term by vacuum extraction delivery without subsequent asphyxia or neonatal jaundice. Birth weight was 2,900 gm. Horizontal pendular nystagmus was observed soon after birth. Developmental milestones were delayed. He developed head control at 7 months, rolled over at 9 months, and sat with support at 1 year, 8 months of age. He has never learned to crawl and stand with support. This patient had 2 previous admissions to other hospitals for poor appetite and poor weight gain, at 4 and 8 months of age, respectively. The following tests were normal: blood gases, electrolytes, thyroid function, electroencephalography (EEG), and cranial computed tomography (CT; Fig 1). No definite diagnosis was determined. Rehabilitation was not effective. On admission, body length was 72 cm (< 3 S.D.), weight 6.9 kg (< 3 S.D.), and head circumference 44.5 cm (< 3 S.D.; Fig 2). There were no abnormalities of the chest, heart, abdomen, or external genitalia. Trunk ataxia, mild hypotonia, head tremor, and 2-3 Hz horizontal pendular nystagmus were observed. Muscle power and auditory behavior responses were normal. Deep tendon reflexes were slightly exaggerated; however, no pathologic reflex was elicited. Normal laboratory tests included blood count, electrolytes, blood gases, liver function, ammonia, blood glucose, pyruvate, lactate, thyroid function, urine amino acid, and urine methylmalonic acid. CK was slightly elevated (161 IU/L) with BB type 9.93%, MB type 11.65%, and MM type 79.01%. Chest and skull radiographs were normal. Bone age was appropriate for age. Sonographic examinations of the kidney and heart were normal. Electromyography failed to disclose myopathy or neuropathy. Auditory brainstem responses stimulated by 4 KHz clicks - - 80 dB (left side) and 90 dB (right side) - - revealed only wave I with absence of the following wave (Fig 3). A child psychiatrist found no evidence of psychosocial factors contributing to the patient's failure-to-thrive.
Discussion The clinical data of our patient and 9 others from the literature are summarized in Table 1. No definite perinatal
Introduction Japanese authors have reported 9 Japanese infants or boys with hypotonia, psychomotor retardation, congenital horizontal pendular nystagmus with head nodding or tremor, and only wave I or waves I and II on auditory brainstem responses (ABRs) [1-3]. These patients often developed spastic diplegia by 2 years of age. A brain lesion with a possible genetic origin was believed to be responsible for this peculiar syndrome. We present a Taiwanese patient with similar clinical manifestations and review the Japanese literature.
Case Report This boy, 1 year, 8 months of age, was admitted to our hospital with nystagmus, growth failure, and psychomotor retardation. There was no family history of consanguinity, congenital anomaly, psychomotor
From the Department of Pediatrics; National Taiwan University Hospital; Taipei, Taiwan; Republic of China.
Figure 1. Normal CT at 8 months of age.
Communications should be addressed to: Dr. Wang; Department of Pediatrics; National Taiwan University Hospital; No. 1 Chang-Teh Street; Taipei, Taiwan; 10006 Republic of China. Received May 1, 1989; accepted August 29, 1989.
Wang et al: Hypotonia and Abnormal ABR
381
mal in 5 patients, while 1 patient had lnild braifl atrophy. The characteristics of these patients included: (1) All males; (2) Congenital nystagmus: (3) Psychomotor retardation: (4) Hypotonia and developed spastic diplegia by 2 years of age; (5) Six patients presented with growth failure (the other 4 patients were not described in the literature); (6) Nonprogressive course; and, (7) Abnormal ABRs revealing only wave I or only waves I and II. Clinically, hypotonia began in early infancy and spastic diplegia by 2 years of age; the nonprogressive courses were similar to cerebral palsy. Because of the occurrence in siblings and male predominance, a genetic origin is suspected. From clinical observation of our patient, growth failure appeared to be related to poor appetite, rather than difficulty in feeding or malabsorption. The precise cause of poor appetite remains unknown. Normal ABRs consist of a sequence of up to 7 waves. Earlier studies attempted to relate wave I to the acoustic nerve, wave II to the cochlear nucleus and trapezoid body, wave III to the superior olive, wave IV to the lateral lemniscus, wave V to the inferior colliculus, wave VI to the medial geniculate body of the thalamus, and wave VII to the medial geniculate body or auditory radiation 14-6]. It is difficult+ however, to make an unequivocal correlation between the individual wave and brainstem structures throughout the direct recordings from the Vicinity of presumed generators in humans [7-9]. It is now believed that most waves are probably generated by more than one anatomic structure and that each structure may contribute to more than one wave. Recent studies also suggested that both waves I and II may relate to the acoustic nerve and type III to the cochlear nucleus [10,1l]. With this interpretation, the most likely site for the generation of wave II or III is the cochlear nucleus; however, the superior olivary nucleus should also be considered. The abnormal ABR findings of only wave I or waves I and II are non-
Figure 2. Appearance of the patient at I year, 8 months ~)/"age revealing growth failure and mild hypotonia.
or postnatal insult was observed in these patients. Patients 7 and 8 are siblings. Patients 2, 3, and 9 presented with seizures and abnormal EEG findings. CT scans were norpvolt -1 1
J
~
,
/
~
_
.
.
.
_
~
.
~
. . . . Right Ear (90 dB)
RI
Left Ear (80 dB) ~a2
81
I
I
I
I
I
M~EC
I
I
l
I
I
Figure 3. ABRs stimulated by 4 KHz clicks--80 dB (left side) and 90 dB (right side)--revealed only wave l with absence of the following waves.
382
PEDIATRIC NEUROLOGY
Vol. 5 No. 6
Table 1. Clinical data of 9 males presenting with hypotonia, nystagmus, psychomotor retardation, and abnormal ABRs Patient No./Ref. No.
Age at Diagnosis (yrs/mos)
Nationality
Birth Weight (gms)
Hypotonia
Growth Failure
Psychomotor Retardation
Auditory Brainstem Responses
1/[ l ]
0/3
Japanese
2,625
+ (NB)
+
?
+
I
2*/[ 1]
0/7
Japanese
2,500
+ (NB)
+
?
+
I
3"/[1]
0/11
Japanese
2,650
+ (3 mos)
+
?
+
I,II
4/[2]
I/0
Japanese
3,590
+
+
+
+
I,II
5/[ 1]
1/1
Japanese
3,500
+
+
?
+
I,II
6/[3]
3/0
Japanese
3,500
+
+
+
+
I,II
7+/[2]
3/1
Japanese
2,750
+ (3 mos)
+
+
+
1,II
8t/[2]
6/1
Japanese
2,950
+
+
+
+
I,II
9*/[2]
8/4
Japanese
2,020
+
+
+
+
I,II
Present patient
1/8
Taiwanese
2,900
+ (NB)
+
+
+
I
Nystagmus
* Patient had seizures. * Patients 7 and 8 are siblings. Abbreviation: NB = Newborn
specific and suggest brainstem lesions, such as posterior fossa tumors, degenerative diseases, and brain death. Based on male predominance and occurrence in siblings, this peculiar syndrome may be attributed to a genetically determined dysgenetic brainstem lesion.
References [1] Kaga K, Yokochi K. Seven infants showing wave I and II of auditory brainstem responses, congenital horizontal nystagmus, and hypotonia. Auditory 1985;28:91-6. [2] Uchida T, Kitazurni E, Yokochi K. Four cases with congenital brainstem lesions. Shonika Shinryo 1985;48:1445-9. [3] Aiba K, Yokochi K, Ishikawa T. A case of ataxic diplegia, mental retardation, congenital nystagmus, and abnormal auditory brainstem responses showing only wave I and II. Brain Dev 1986;8:630-2. [4] Starr A, Achor J. Auditory brainstem responses in neurological disease. Arch Neurol 1975;32:761-8.
[5] Starr A, Hamilton AE. Correlation between confirmed sites of neurological lesions and abnormalities of far-field auditory brainstem responses. Electroencephalogr Clin Neurophysiol 1976;41:595-608. [6] Stockard JJ, Rossiter VS. Clinical and pathologic correlates of brainstem auditory response abnormalities. Neurology 1977;27:316-25. [7] Hashimoto I. Auditory evoked potentials from the human midbrain: Slow b r a i n s t e m responses. E l e c t r o e n c e p h a l o g r Clin Neurophysiol 1982;53:652-7. [8] Moiler AR, Jannetta PJ. Evoked potentials from the inferior colliculus in man. Electroencephalogr Clin Neurophysiol 1982;53: 612-20. [9] Moiler AR, Jannetta PJ. Interpretation of brainstem auditory evoked potentials: Results from intracranial recordings in humans. Scand Audiol 1983; 12:125-33. [10] Hashimoto I, Ishiyama Y, Yoshimoto I, Nemoto S. Brain-stem auditory-evoked potentials recorded directly from human brain-stem and thalamus. Brain 1981;104:841-59. [11] M011er AR, Jannetta PJ. Auditory evoked potentials recorded from the cochlear nucleus and its vicinity in man. J Neurosurg 1983; 59:1013-8.
Wang et al: Hypotonia and Abnormal ABR
383
A Taiwanese boy, 1 year, 8 months of age, is reported with poor weight gain, hypotonia, trunk ataxia, motor developmental retardation, and horizontal pendular nystagmus with only wave I on auditory brainstem responses. Our patient clinically resembled 9 patients reported in the Japanese literature. Because of its male predominance, occurrence in siblings, early onset, nonprogressive course, and characteristic auditory brainstem response findings, the syndrome may be of genetic origin and attributable to a dysgenetic brainstem lesion. Wang P-J, Chen R-L, Shen Y-Z. Hypotonia, congenital nystagmus, and abnormal auditory brainstem response. Pediatr Neurol 1989;5:381-3.
retardation, or other relevant diseases. He was born at term by vacuum extraction delivery without subsequent asphyxia or neonatal jaundice. Birth weight was 2,900 gm. Horizontal pendular nystagmus was observed soon after birth. Developmental milestones were delayed. He developed head control at 7 months, rolled over at 9 months, and sat with support at 1 year, 8 months of age. He has never learned to crawl and stand with support. This patient had 2 previous admissions to other hospitals for poor appetite and poor weight gain, at 4 and 8 months of age, respectively. The following tests were normal: blood gases, electrolytes, thyroid function, electroencephalography (EEG), and cranial computed tomography (CT; Fig 1). No definite diagnosis was determined. Rehabilitation was not effective. On admission, body length was 72 cm (< 3 S.D.), weight 6.9 kg (< 3 S.D.), and head circumference 44.5 cm (< 3 S.D.; Fig 2). There were no abnormalities of the chest, heart, abdomen, or external genitalia. Trunk ataxia, mild hypotonia, head tremor, and 2-3 Hz horizontal pendular nystagmus were observed. Muscle power and auditory behavior responses were normal. Deep tendon reflexes were slightly exaggerated; however, no pathologic reflex was elicited. Normal laboratory tests included blood count, electrolytes, blood gases, liver function, ammonia, blood glucose, pyruvate, lactate, thyroid function, urine amino acid, and urine methylmalonic acid. CK was slightly elevated (161 IU/L) with BB type 9.93%, MB type 11.65%, and MM type 79.01%. Chest and skull radiographs were normal. Bone age was appropriate for age. Sonographic examinations of the kidney and heart were normal. Electromyography failed to disclose myopathy or neuropathy. Auditory brainstem responses stimulated by 4 KHz clicks - - 80 dB (left side) and 90 dB (right side) - - revealed only wave I with absence of the following wave (Fig 3). A child psychiatrist found no evidence of psychosocial factors contributing to the patient's failure-to-thrive.
Discussion The clinical data of our patient and 9 others from the literature are summarized in Table 1. No definite perinatal
Introduction Japanese authors have reported 9 Japanese infants or boys with hypotonia, psychomotor retardation, congenital horizontal pendular nystagmus with head nodding or tremor, and only wave I or waves I and II on auditory brainstem responses (ABRs) [1-3]. These patients often developed spastic diplegia by 2 years of age. A brain lesion with a possible genetic origin was believed to be responsible for this peculiar syndrome. We present a Taiwanese patient with similar clinical manifestations and review the Japanese literature.
Case Report This boy, 1 year, 8 months of age, was admitted to our hospital with nystagmus, growth failure, and psychomotor retardation. There was no family history of consanguinity, congenital anomaly, psychomotor
From the Department of Pediatrics; National Taiwan University Hospital; Taipei, Taiwan; Republic of China.
Figure 1. Normal CT at 8 months of age.
Communications should be addressed to: Dr. Wang; Department of Pediatrics; National Taiwan University Hospital; No. 1 Chang-Teh Street; Taipei, Taiwan; 10006 Republic of China. Received May 1, 1989; accepted August 29, 1989.
Wang et al: Hypotonia and Abnormal ABR
381
mal in 5 patients, while 1 patient had lnild braifl atrophy. The characteristics of these patients included: (1) All males; (2) Congenital nystagmus: (3) Psychomotor retardation: (4) Hypotonia and developed spastic diplegia by 2 years of age; (5) Six patients presented with growth failure (the other 4 patients were not described in the literature); (6) Nonprogressive course; and, (7) Abnormal ABRs revealing only wave I or only waves I and II. Clinically, hypotonia began in early infancy and spastic diplegia by 2 years of age; the nonprogressive courses were similar to cerebral palsy. Because of the occurrence in siblings and male predominance, a genetic origin is suspected. From clinical observation of our patient, growth failure appeared to be related to poor appetite, rather than difficulty in feeding or malabsorption. The precise cause of poor appetite remains unknown. Normal ABRs consist of a sequence of up to 7 waves. Earlier studies attempted to relate wave I to the acoustic nerve, wave II to the cochlear nucleus and trapezoid body, wave III to the superior olive, wave IV to the lateral lemniscus, wave V to the inferior colliculus, wave VI to the medial geniculate body of the thalamus, and wave VII to the medial geniculate body or auditory radiation 14-6]. It is difficult+ however, to make an unequivocal correlation between the individual wave and brainstem structures throughout the direct recordings from the Vicinity of presumed generators in humans [7-9]. It is now believed that most waves are probably generated by more than one anatomic structure and that each structure may contribute to more than one wave. Recent studies also suggested that both waves I and II may relate to the acoustic nerve and type III to the cochlear nucleus [10,1l]. With this interpretation, the most likely site for the generation of wave II or III is the cochlear nucleus; however, the superior olivary nucleus should also be considered. The abnormal ABR findings of only wave I or waves I and II are non-
Figure 2. Appearance of the patient at I year, 8 months ~)/"age revealing growth failure and mild hypotonia.
or postnatal insult was observed in these patients. Patients 7 and 8 are siblings. Patients 2, 3, and 9 presented with seizures and abnormal EEG findings. CT scans were norpvolt -1 1
J
~
,
/
~
_
.
.
.
_
~
.
~
. . . . Right Ear (90 dB)
RI
Left Ear (80 dB) ~a2
81
I
I
I
I
I
M~EC
I
I
l
I
I
Figure 3. ABRs stimulated by 4 KHz clicks--80 dB (left side) and 90 dB (right side)--revealed only wave l with absence of the following waves.
382
PEDIATRIC NEUROLOGY
Vol. 5 No. 6
Table 1. Clinical data of 9 males presenting with hypotonia, nystagmus, psychomotor retardation, and abnormal ABRs Patient No./Ref. No.
Age at Diagnosis (yrs/mos)
Nationality
Birth Weight (gms)
Hypotonia
Growth Failure
Psychomotor Retardation
Auditory Brainstem Responses
1/[ l ]
0/3
Japanese
2,625
+ (NB)
+
?
+
I
2*/[ 1]
0/7
Japanese
2,500
+ (NB)
+
?
+
I
3"/[1]
0/11
Japanese
2,650
+ (3 mos)
+
?
+
I,II
4/[2]
I/0
Japanese
3,590
+
+
+
+
I,II
5/[ 1]
1/1
Japanese
3,500
+
+
?
+
I,II
6/[3]
3/0
Japanese
3,500
+
+
+
+
I,II
7+/[2]
3/1
Japanese
2,750
+ (3 mos)
+
+
+
1,II
8t/[2]
6/1
Japanese
2,950
+
+
+
+
I,II
9*/[2]
8/4
Japanese
2,020
+
+
+
+
I,II
Present patient
1/8
Taiwanese
2,900
+ (NB)
+
+
+
I
Nystagmus
* Patient had seizures. * Patients 7 and 8 are siblings. Abbreviation: NB = Newborn
specific and suggest brainstem lesions, such as posterior fossa tumors, degenerative diseases, and brain death. Based on male predominance and occurrence in siblings, this peculiar syndrome may be attributed to a genetically determined dysgenetic brainstem lesion.
References [1] Kaga K, Yokochi K. Seven infants showing wave I and II of auditory brainstem responses, congenital horizontal nystagmus, and hypotonia. Auditory 1985;28:91-6. [2] Uchida T, Kitazurni E, Yokochi K. Four cases with congenital brainstem lesions. Shonika Shinryo 1985;48:1445-9. [3] Aiba K, Yokochi K, Ishikawa T. A case of ataxic diplegia, mental retardation, congenital nystagmus, and abnormal auditory brainstem responses showing only wave I and II. Brain Dev 1986;8:630-2. [4] Starr A, Achor J. Auditory brainstem responses in neurological disease. Arch Neurol 1975;32:761-8.
[5] Starr A, Hamilton AE. Correlation between confirmed sites of neurological lesions and abnormalities of far-field auditory brainstem responses. Electroencephalogr Clin Neurophysiol 1976;41:595-608. [6] Stockard JJ, Rossiter VS. Clinical and pathologic correlates of brainstem auditory response abnormalities. Neurology 1977;27:316-25. [7] Hashimoto I. Auditory evoked potentials from the human midbrain: Slow b r a i n s t e m responses. E l e c t r o e n c e p h a l o g r Clin Neurophysiol 1982;53:652-7. [8] Moiler AR, Jannetta PJ. Evoked potentials from the inferior colliculus in man. Electroencephalogr Clin Neurophysiol 1982;53: 612-20. [9] Moiler AR, Jannetta PJ. Interpretation of brainstem auditory evoked potentials: Results from intracranial recordings in humans. Scand Audiol 1983; 12:125-33. [10] Hashimoto I, Ishiyama Y, Yoshimoto I, Nemoto S. Brain-stem auditory-evoked potentials recorded directly from human brain-stem and thalamus. Brain 1981;104:841-59. [11] M011er AR, Jannetta PJ. Auditory evoked potentials recorded from the cochlear nucleus and its vicinity in man. J Neurosurg 1983; 59:1013-8.
Wang et al: Hypotonia and Abnormal ABR
383