Gastroesophageal Dysfunction in Cornelia de Lange Syndrome

By Michelle Cates, Deborah F. Billmire, Marilyn J. Bull, and Jay L. Grosfeld Indianapolis, Indiana

�9 Children with Cornelia de Lange (CDL) syndrome present with feeding problems related to swallowing incoordination, poor esophageal motility, and gastro- esophageal reflux (GER). These abnormalities of esopha- geal function result in failure to thrive and lifethreatening aspiration pneumonia. Severe GER was documented in four patients with CDL syndrome. Three were managed success- fully with an antireflux procedure (Nissen fundoplication) and a concomitant feeding gastrostomy. These observa- tions confirm the high incidence of abnormal esophageal function in patients with CDL syndrome, and suggest that an antireflux procedure and feeding gastrostomy are important considerations in their clinical mangement. �9 1989 by Grune & Strat ton, Inc.

INDEX WORDS: Cornelia de Lange syndrome; gastro- esophageal reflux; Nissen fundoplication; disordered eso- phageal motility.

M ORE THAN 250 cases of Cornelia de Lange (CDL) syndrome have been reported since

1933 when the first patients with this condition were described by the Dutch pediatrician, Cornelia de Lange. ~ Although the hallmarks of the syndrome consist of characteristic facial features and skeletal anomalies, gastrointestinal (GI) malformation and malfunction frequently accompany this disorder. 2 In fact, GI complications are the second most frequent cause of death in these children?

Little information regarding CDL syndrome is available in the surgical literature. The recognition of significant gastroesophageal reflux (GER) in four of five children with CDL syndrome followed at the James Whitcomb Riley Hospital for Children in Indi- anapolis prompted this report. The purpose of this article is to acquaint the surgeon with the clinical manifestations of this syndrome and to suggest that an antireflux operation may be a lifesaving procedure.

CASE REPORTS

Patient 1

A 5-year-old white girl with CDL syndrome had microcephaly, typical facial features, two ulnar digits absent on the left hand (Fig 1), growth and developmental delay, and a seizure disorder. A

From the Section of Pediatric Surgery, Department of Surgery, Indiana University School of Medicine and the James Whitcomb Riley Hospital for Children, Indianapolis.

Address reprint requests to Jay L. Grosfeld, MD, Surgeon- in-Chief J.W. Riley Hospital for Children (K21), 702 Barnhill Dr, Indianapolis, IN 46223.

�9 1989 by Grune & Stratton, Inc. 0022-3468/89/2403-0004503.00/0

pyloromyotomy was performed at 8 weeks of age for hypertrophic pyloric stenosis. She had symptomatic GER since early infancy with frequent vomiting after feedings and recurrent episodes of right middle lobe pneumonia. Initial treatment with thickened feedings, antacids, and bethanechol resulted in some improvement; however, severe symptoms recurred by the time the baby was 21/2 years of age. Evaluation at that time with an upper GI contrast study showed nasopharyngeal reflux (Fig 2), poor esophageal motility, an aberrant right subclavian artery (Fig 3), and significant GER to the level of the upper esophagus. A Nissen fundoplication procedure and gas- trostomy were performed. The girl required an emergency laparot- omy on the third postoperative day for a bowel obstruction that was due to mid-small bowel intussusception. This was successfully treated by intraoperative manual reduction, and her subsequent course was uneventful. She was last seen 2 years postoperatively without any further vomiting or pneumonia and tolerating gas- trostomy feedings.

Patient 2

A full-term small-for-gcstational-age black male was diagnosed with CDL syndrome in the newborn period with a number of anomalies including the absence of radii and three ulnar digits, a heart murmur, microcephaly, typical facial features of CDL syn- drome, growth failure, and mental retardation. He was followed sporadically in the outpatient clinic until he was 5 years of age and was admitted with pneumonia, bronchospasm, and iron deficiency anemia. An upper GI contrast study showed very poor esophageal motility, and a hiatal hernia with GER to the level of the upper esophagus. Despite conservative medical treatment with upright and inclined positioning, antacids, and bethanccbol, persistent vomiting was noted, which prevented adequate caloric intake. A Nisscn fundoplication and gastrostomy were performed when the boy was 5 years and 3 months of age. The patient was last seen 9 months postoperatively with no evidence of vomiting or aspiration pneumo- nia. Nutrition was maintained with gastrostomy feedings.

Patient 3

A 14-month-old white boy was diagnosed as having CDL syn- drome at 5 months of age. He presented with typical facies, growth retardation, and developmental delay. Feeding problems were noted shortly after birth with the baby spitting up formula; this led to frequent episodes of nonbitious vomiting by 7 months of age. No history of wheezing or pneumonia was elicited. A barium csophago- gram showed significant GER to the level of the thoracic inlet with no evidence of esophageal dysmotility or aspiration. At fiberoptic esophagoscopy, marked friability of the entire length of the esopha- geal mucosa was noted with exudate and ulceration in the distal third consistent with severe reflux esophagitis. When the baby was 14 months old, a Nissen fundoplication and placement of a Stamm gastrostomy were performed without complication. At 10 months postoperatively, the boy has been doing well except for one episode of Streptococcus pneumoniae bacteremia that responded to antibiotics. Feedings are well tolerated through the gastrostomy tube.

Patient 4

This 2J/2-year-old white girl was diagnosed in early infancy as having CDL syndrome. This was associated with microcephaly, typical facies, growth retardation, flexion contractures of both

248 Journal of Pediatric Surgery, Vol 24, No 3 (March), 1989: pp 248-250

GER IN CORNELIA OE LANGE SYNDROME 249

Fig 1. Left hand of pat ient 1 with absent ulnar digits.

elbows, cleft palate, and a heart murmur. She had experienced episodes of vomiting following meals since early infancy. An upper GI contrast swallow at 10 months of age showed nasopharyngeal reflux, poor esophageal motility with distal esophageal spasm, and an aberrant right subclavian artery. The parents refused an opera- tion and desired to continue attempts at conservative management. Repeat contrast studies were performed when she was 22 months of age for persistent vomiting. The findings were similar, and in addition, GER and some aspiration were observed. At 27 months of age, she remains symptomatic with vomiting, but has had no history of pneumonia.

DISCUSSION

The characteristic features of CDL syndrome include low birth weight, growth retardation, develop- mental delay, hirsutism, and typical morphologic fea- tures. 3,4

The typical facies are microcephaly, synostosis, a low hairline, anteverted nostrils, thin lips, and a long philtrum. Upper limb anomalies, including absent radii and ulnar digits, are also commonly observed. The diagnosis is based on recognition of the typical pattern of anomalies. There is neither an associated chromosomal abnormality nor a recognized pattern of inheritance.

Feeding difficulties have been recorded in 70% to 100% of reported cases. 2,5 These include frequent eme- sis, swallowing incoordination, and aspiration. Func- tional abnormalities on upper GI contrast studies include nasopharyngeal reflux, poor esophageal motili- ty, and significant GER. Structural anomalies of the GI tract have also been observed including pyloric stenosis, duodenal stenosis, malrotation, and intestinal duplications. 2'6 These problems may contribute to the morbidity and mortality observed in patients with CDL syndrome. Respiratory (aspiration) and GI com- plications are the two most common causes of mortali- ty. 3

The four patients examined in this study confirm the high incidence of GER and feeding difficulties observed in this group of children. Lachmann et aP also documented the frequency of pathologic GER and stressed the important therapeutic value of an antire- flux procedure in reducing the risk of aspiration and esophageal stricture from longstanding acid reflux.

Although a successful antireflux operation prevents aspiration of gastric contents, dysfunctional swallow- ing and poor esophageal motility may be a continued cause of pulmonary complications. These latter find-

250 CATES ET AL

Fig 2. Massive nasopharyngeal reflux during barium swallow,

ings, in association with underlying growth retarda- tion, suggest that use of gastrostomy feedings may be advantageous in the overall management of patients with CDL syndrome. Gastrostomy feedings resulted in improved caloric intake and maintained nutrition in all three infants reported herein who underwent surgery.

These observations indicate the need to fully evalu- ate the nature of feeding difficulties in children with CDL syndrome. Our findings suggest that the optimal management of symptomatic GER in the neurologi- cally impaired patient with CDL syndrome includes a Nissen fundoplication procedure and concomitant Stamm gastrostomy placement. 7

Fig 3. Upper GI contrast study shows posterior esophageal impression due to aberrant right subclavian artery.

REFERENCES

1. Lachman R, Funamura J, Szalay G: Gastrointestinal abnor- malities in the Cornelia de Lange syndrome. Mt Sinai J Med 48:236-240, 1981

2. Schlesinger B, Clayton B, Bodiar M, et al: Typus degenera- tiuus amstelodamensis. Arch Dis Child 38:349-357, 1963

3. Berg JM, McCreary BD, Ridler MAC, et al: The de Lange Syndrome. Pergamon, 1970, pp 109-115

4. Abraham JM, Russell A: de Lange syndrome: A study of nine examples. Acta Paediatr Scand 57:339-353, 1968

5. Hawley DP, Jackson LG, Kurmit DM: Sixty-four patients with Brachmann-de Lange syndrome: A survey. Am J Med Genet 20:453-459, 1983

6. Kurlander G J, DeMyer W: Roentgenology of the Brachmann- de Lange syndrome. Radiology 88:101-110, 1957

7. Dedinsky GK, Vane DW, Black CT, et al: Complications and reoperation after Nissen fundoplication in childhood. Am J Surg 153:177+183, 1987