DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1980,22

ZUSAMMENFASSUNG Angeborene Arrhrogryposis multiplex hervorgerufen durch eine angeborene Myasthenie Verminderte fetale Bewegungen konnen eine Arhrogryposis multiplex hervorrufen. Es

gibt mehrere bestimmte neuromuskulare Erkrankungen, die als Ursache fur dieses Syndrom in Frage kommen; die angeborene Myasthenie ist bisher jedoch nicht als mogliche Ursache in Betracht gezogen worden. Die Autoren berichten uber einen Fall einer angeborenen Myasthenie, die zu einer Arthrogryposis multiplex gefiihrt hat.

RESUMEN Artrogriposis mu’ltiple conghita debida a miastenia congknita

La disminuci6n de movimientos fetales puede causar artrogriposis mliltiple congknita. Diversas alteraciones neuromusculares diferentes pueden causar este sindrome, per0 la miastenia conghi ta no ha sido considerada como una causa posible. Los autores aportan un caso de miastenia congknita que dio lugar a una artrogriposis mliltiple congknita.

REFERENCES Brooke. M. H. (1973) ‘Coneenital fiber tvoe diserooortion.’ In: Kakulas. B. A. fEd.) Proceedings o f the

2nd International Congre; on Muscul~; Diseise;, Purr 2: Clinical Studies i n Myology. Amiterham: Excerpta Medica. pp. 147-159.

- Engel, W. K. (1969) ‘ The histiographic analysis of human muscle biopsies with regard to fiber types. I: Adult male and female.’ Neurology, 19, 221-233.

Byers, R. K., Banker, B. Q. (1961) ‘Infantile muscular atrophy.’ Archives of Neurology, 5, 140-164. Clarke, R. R., van de Velde, R. L. (1971) ‘Congenital myasthenia gravis.’ American Journal of Diseuses of Children. 122, 356-361.

Colling-Salting, A. (1978) ‘Enzyme histochemistry on skeletal muscle of the human fetus.’ Journal of the Neurological Sciences, 39, 169- 185.

Donner, M., Rapola, J., Somer, H. (1975) ‘Congenital muscular dystrophy.’ Neuropadiatrie, 6, 239-258. Drachman. D. B. f1971) ‘The svndrome of arthrogrvDosis multiolex coneenita.’ Birth Defects. Oriainal -.

Article Series, 7,‘(2), 90-97. . - Y

- Banker. B. 0. f 1961) ‘Arthrogryposis multiplex congenita.’ Archives o/ Neurology. 5, 77-93. Jago, R. H. (1970) ‘Arthrogryposis’ following -treatment of maternal tetanus with- muscle relaxants.’

Krugliak, L., Gadoth, N., Behar, A. ( 1978) ‘Neuropathic forms of arthrogryposis multiplex congenita.’ Archives of Disease in Childhood, 45, 277-279.

Journal o the Neurological Sciences, 37, 179- 185.

multiple congenital anomalies.’ Journal of Pediatrics, 94, 47-5 1.

and adolescence.’ Neurology, 10, 1007-1014.

and the neonate.’ Archives of Neurology, 33, 459-465.

myasthenia gravis.’ Lancet, 1, 441-442.

McComb, R . D., Markesbury, W. R., O’Connor, w. N. (1979) ‘Fatal neonatal nemaline myopathy with

Millichap, J. C., Dodge, P. R. (1960) ‘Diagnosis and treatment of myasthenia gravis in infancy, childhood

Sarnat, H. B., O’Connor, T., Byrne, P. A. (1976) ‘Clinical effects of myotonic dystrophy on pregnancy

Vincent, A,, Newson-Davies, J. (1979) ‘Absence of anti-acetylcholine receptor antibodies in congenital

Sandifer Syndrome: an Unappreciated Clinical Entity

Steven L. Werlin Bernard J. D’Souza Walter J. Hogan Wylie J. Dodds Ronald C. Arndorfer

Introduction Since the first description of the Sandifer

syndrome (Kinsbourne and Oxon 1964),

Correspondence to Steven L. Werlin, M.D., Department of Pediatrics, Milwaukee Children’s Hospital, 1700 West Winconsin Avenue, Mil- waukee, Wisconsin 53233.

374

only a few reports of the symptom complex of hiatal hernia, gastro-esophageal reflux, body posturing and torticollis have appeared in the medical literature (Sutcliffe 1969, Gellis and Feingold 197 1, Bray et al. 1977, Murphy and Gellis 1977). Children with this condition are frequently

CASE REPORTS

considered to have a primary neurological disease (Snyder 1969, Chutorian 1974, CASE 1 Bray et a/. 1977); consequently, early A two-week-old girl was admitted to hospital

for episodes of body stiffening followed by apnea,

disorder is important if were preceded by coughing, sneezing and emesis. exhaustive neurological investigations are Full extension of all extremities occurred during to be avoided. Further, accurate diagnosis the apneic spells. Laboratory evaluation, in- of the Sandifer syndrome allows ap- cluding blood and cerebrospinal fluid cultures

and EEG, were normal. An upper gastro- propriate therapy for this benign 'On- intestinal series demonstrated reflux of the barium dition: response to treatment generally is from the stomach into the esophagus. On excellent . esophageal manometric study, resting lower

We report five cases of the syndrome. esophageal sphincter pressure was IOmmHg. Esophageal manometric studies and Multiple episodes of spontaneous gastro-

esophageal reflux were demonstrated by an intraluminal pH monitoring were intraluminal pH electrode. Ten minutes after the in confirming the diagnosis* I n One subcutaneous injection of bethanechol (0.075mg/ patient, gastro-esophageal reflux was kg). lower esophageal sphincter pressure rose to demonstrated only by intraluminal pH 38mmHg. After the bethanechol injection monitoring. spontaneous reflux no longer occurred. Eso-

phageal peristalsis was normal. She was treated with antireflux measures, consisting of 'thickened'

Method feedings and upright positioning in an infant seat. Esophageal manometric studies were No further episodes of postural abnormalities or

performed according to the methods apnea have been noted during a follow-up period described by Dodds (1976) and Arndorfer Of six months. ef a/. (1977). We now use a 9-lumen CASE manometric tube assembly, only 4.5mm in A 16day-old girl was admitted to the hospital outer diameter. A pH probe to measure for evaluation of three episodes of shaking, intraluminal esophageal pH, inserted body stiffening, and hyperextension of both arms, through the central lumen, emerges from followed by limpness. These episodes occurred

only after feeding and were associated with the assembly via a side port located 3cm emesis. During her hospital admission the infant above a sleeve Sensor 4cm in length, which regurgitated after most feedings. An EEG was is used to monitor lower esophageal normal but an upper gastro-intestinal series sphincter pressure. When positioned demonstrated gastro-esophageal reflux. Despite

sphincter pressure and normal peristalsis on the 4cm-s1eeve records i ts pressure manometry, on several occasions the pH electrode continuously, despite axial ITwement of recorded a sudden drop in intraluminal pH, the esophagus during respiration and associated with transient inappropriate lower swallowing (Dent 1976). Six lateral esophageal sphincter relaxation during constant recording orifices are spaced Over a gcm monitoring of the gastro-esophageal junction

with the sleeve sensor. The patient was treated

pressure activity in the esophageal body. Vomiting stopped and no further episodes of Another recording orifice at the distal abnormal posturing have occurred during the margin of the sleeve records intragastric past nine months. pressure. During pressure recording, the

CASE 3 assembly lumens are infused slowly with An eight-month-old girl was referred for water (O' 5m1'min) by a pneumohydraulic evaluation of torticollis. The medical history infusion Pump with minimum compliance revealed postprandial regurgitation during the (Arndorfer er a/. 1977). previous two months, but the torticollis could

Case reports

recognition Of the pathophysiology Of the occurring Over a 48-hour period. These episodes

straddling the lower esophageal sphincter, the demonstration of normal lower esophageal

segment above the 'Ieeve device to record with 'thickened' feedings and upright positioning,

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not be related to the regurgitation. Results of a physical examination, including a complete neurological evaluation, were normal. An upper gastro-intestinal series failed to show either gastro-esophageal reflux or a hiatal hernia. Esophageal manometric study demonstrated normal peristalsis, and the lower esophageal sphincter pressure was 28mmHg. Esophageal pH monitoring did not record any episodes of gastro- esophageal reflux during a 30-minute observation period. Because gastro-esophageal reflux may be intermittent and the patient was fasting for the study, esophagoscopy was performed. Esophagitis was observed in the distal 3cm of the esophagus. The patient was treated with antacids, 'thickened' feedings and upright posture in an infant seat. Complete resolution of the torticollis occurred within one month and has persisted.

CASE 4 A 12-week-old boy was admitted for evaluation

of recurrent vomiting. Previous diagnostic evaluation had included three normal upper gastro-intestinal series, as well as normal skull X-rays, CT scan and EEG. Formula changes had not been helpful. On the day before admission the infant experienced three episodes of shaking, thought to be seizures by the parents. Results of physical and neurological examinations were normal, as was the EEG. Esophageal manometric evaluation revealed normal esophageal motor function; the lower esophageal sphincter pressure was 46mmHg. However, episodes of gastro- esophageal reflux were shown by esophageal pH monitoring. He was treated with 'thickened' feedings and upright positioning. Vomiting decreased dramatically. Three weeks after discharge, another episode of pseudo-seizures, associated with vomiting, occurred at home. He has remained well for the ensuing five months.

CASE 5 A nine-day-old girl was admitted to hospital

for episodes of apnea, shaking, cyanosis and choking during the previous three days. These episodes were followed by vomiting of white mucus and food. The child otherwise had been well. Blood and cerebrospinal fluid cultures were negative. Upper gastro-intestinal X-ray series showed gastro-esophageal reflux. A technecium sulfur-colloid scan revealed reflux of the nuclide to the level of the pharynx. Esophageal manom- etric evaluation showed lower esophageal sphincter pressure of 35mmHg, and normal peristalsis. Spontaneous gastro-esophageal reflux was recorded by the intraluminal pH electrode.

Infusions of 0.5ml of 0.1 NHCI into the distal, mid, and proximal esophagus were followed by emesis. Control infusions of saline had no effect. The infant was treated with upright positioning and 'thickened' feedings, with resolution of all symptoms. She has remained well for five months. At age five months esophageal motility was re-evaluated and was found to be normal. Gastro- esophageal reflux was not elicited and the sensitivity to acid was no longer present.

Discussion The early reports of Sandifer syndrome

stressed the association of hiatal hernia with dystonic posturing (Kinsbourne 1964, Sutcliffe 1969, Gellis and Feingold 1971). Additionally, mild cases with only torticollis have been reported (Murphy and Gellis 1977). Recent reports indicate that dystonic posturing may be associated with gastro-esophageal reflux even when a hiatal hernia is not demonstrated (Murphy and Gellis 1977, Bray el a/. 1977). A hiatal hernia was not demonstrated in any of our patients, therefore demonstration of a hiatal hernia is not a requirement for the diagnosis of Sandifer syndrome.

Although the precise etiology of the syndrome remains unknown, it is ex- tremely important for the physician to recognize the patient with Sandifer s y n d r o m e . Ant iconvulsant t h e r a p y invariably fails, but treatment of the underlying gastro-esophageal reflux will eliminate the symptoms (Bray et al. 1977). Treatment of the gastro-esophageal reflux will also decrease the risk of the complica- tions and reflux, such as aspiration pneumonia, hematemesis and esophageal stricture. Additionally, the added expense of exhaustive neurological evaluation becomes unnecessary.

The body posturings of patients with Sandifer syndrome are believed to represent a response to discomfort associated with gastro-esophageal reflux. However, the posturings may increase the reflux (Kinsbourne 1964). Acid perfusion of the esophagus, performed in only one

376

CASE REPORTS

patient (Case 9, demonstrated extreme sensitivity to small quantities of acid. It is possible that other children with this syndrome have an acute esophageal sensitivity to refluxed gastric contents, so that minimal exposure of the esophagus to acid may initiate all or part of the symptom complex.

We believe that the Sandifer syndrome is more common than generally recog- nized. The cases reported here were seen within a one-year period. Infants and children with torticollis, dystonic postur- ing or atypical seizures should be evaluated for Sandifer syndrome if results of neurological examination are normal, especially when there is a history of vomiting. Although gastro-esophageal reflux may frequently be diagnosed by upper gastro-intestinal series, at times more sophisticated studies-such as

techneciurn scintiscans, intraluminal pH monitoring or esophagoscopy-may be needed to confirm the diagnosis. Medical treatment is the treatment of choice unless there are severe complications of gastro- esophageal reflux: it is simple, relatively short-term and usually successful.

Acknowkdgement: We are indebted to Drs. June Dobbs and Carl Eisenberg for referring Cases 4 and 5 respectively, and to Mrs. Pauline King for typing the manuscript.

This Study was supported in part by USPHS Grant No. AM 15540.

AUTHORS' APPOINTMENTS Steven L . Werlin, M.D., Assistant Professor of Pediatrics; Bernard J. D'Souza, M.D., Assistant Professor of Neurology; Walter J. Hogan, M.D., Professor of Medicine; Wylie J. Dodds. M.D., Professor of Radiology; Ronald C. Arndorfer; The Medical College of Wisconsin, Milwaukee, Wisconsin.

SUMMARY Five cases of Sandifer syndrome are reported, and the authors suggest that frequently

the diagnosis may be overlooked, especially when the patient has a milder or incomplete form of the syndrome. None of the children had hiatal hernia, so this is not an essential requirement for the syndrome. The findings in these five cases suggest that the abnormal posturing associated with this syndrome may be the result of extreme sensitivity of the esophagus to refluxed gastric acid.

RESUME Le syndrome de Sandifer: une entit4 clinique dkprkcike

Cinq cas de syndrome de Sandifer sont rapportks et les auteurssuggkrent que le diagnostic peut t tre souvent nkgligt, spkcialement quand le malade prksente une forme lkgkre ou incompltte du syndrome. Aucun des enfants n'avaient de hernie hiatale et celle-ci n'est donc pas une manifestation essentielle du syndrome. Les donnkes des cinq cas suggkrent que les postures anormales assocites au syndrome peuvent Etre le rksultat de 1'extrEme sensibilitt de I'oesophage au reflux d'acide gastrique.

ZUSAMMENFASSUNG Sandifer Syndrom: ein wenig beachtetes klinisches Bild

Es wird uber funf Falle mit einem Sandifer Syndrom berichtet. Die Autoren sind der Ansicht, da13 die Diagnose vermutlich haufig nicht gestellt wird, besonders dann, wenn der Patient eine mildere oder inkomplette Form des Syndroms aufweist. Keines der Kinder hatte eine Hiatushernie, diese ist also fur das Syndrom nicht ausschlaggebend. Die Befunde dieser funf Falle lassen vermuten, daR die Fehlhaltung, die bei diesem Syndrom

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DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1980,22

auftritt, moglicherweise mit der starken Empfindlichkeit des Oesophagus gegen die aufsteigende Magensaure zusammenhangt.

RESUMEN Sindrome de Sandifer: una entidad clinica no apreciada

Se aportan cinco casos de sindrome de Sandifer y 10s autores sugieren que con frecuencia el diagnbstico puede ser pasado por alto, especialmente cuando el paciente tiene una forma menor o incompleta del sindrome. Ninguno de 10s niiios tenia una hernia de hiato, por lo que iste no es un requisito esencial para el sindrome. Los hallazgos en 10s cinco casos sugieren que la anomalia postural asociada con este sindrome puede ser el resultado de un a extrema sensibilidad del es6fago a1 reflujo hcido ghstrico.

REFERENCES Arndorfer, R. C., Stef, J. J., Dodds, W. J. , Linehan, J . H., Hogan, W. J. (1977) ‘Improved infusion system

Bray, P. F., Herbst, J. J., Johnson, D. G., Book, L. S . , Ziter, P. A., Condon, V. R. (1977) ‘Childhood

Chutorian, A. M. (1974) ‘Benign paroxysmal torticollis, tortipelvis, and retrocollis of infancy.’ Neurology,

Dent, J. (1976) ‘A new technique for continuous sphincter pressure measurement.’ Gasrroenterology,

Dodds, W. J. (1976) ‘Instrumentation and methods for intraluminal esophageal manometry.’ Archives

Gellis, S. S. , Feingold, M. (1971) ‘Syndrome of hiatus hernia with torsion spasms and abnormal posturing.’

Kinsbourne, M., Oxon, D. M. (1964) ‘Hiatus hernia with contortions of the neck.’ Lancet. 1, 1058-1061. Murphy, W. J., Gellis, S. S. (1977) ‘Torticollis with hiatus hernia in infancy, Sandifer syndrome.’ American

Snyder, C. H. (1969) ‘Paroxysmal torticollis in infancy.’ American Journal of Diseases of Children. 117,

Sutcliffe, J. (1969) ‘Torsion spasms and abnormal postures in children with hiatus hernia, Sandifer’s

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24, 366-367.

71, 263-267.

of Internal Medicine, 136, 5 15-523.

American Journal of Diseases of Children, 121, 43-54.

Journal of Diseases of Children, 131, 564-565.

458-460.

syndrome.’ Progress in Pediatric Radiology, 2, 190- 197.

378