Regrowth of tongue following reduction glossoplasty in the neonatal period for Beckwith-Wiedemann macroglossia

Case Report

A 24-year-old female gravida 4, para 2, aborta 1 patient was referred to our centre at 32 weeks gestation for pre-eclampsia. There was no history of maternal diabetes. An obstetrical ultrasound demonstrated fetal macroglossia and a frank breech presentation. BeckwithWiedemann syndrome was suspected. The parents were nonconsanguineous and of normal height and appearance, and their two children were also normal with respect to birth and development.

Due to worsening maternal pre-eclampsia, the female fetus was delivered by cesarean section. Oral endotracheal intubation was performed in the delivery room for anticipated airway obstruction. Apgar scores were 4 and 7 at 1 and 5 minutes, respectively. The placenta was noted to be large. The child was macrosomic (weight 2.63 kg; head circumference 29.5 cm; length 49.5 cm) and had obvious macroglossia, with inability to retract the tongue into the mouth. Umbilical root enlargement (3 cm) and earlobe pits were present. On palpation, the kidneys were assessed as being enlarged. A grade II systolic murmur was present at the left sternal border. The pulse pressure was widened. The initial serum glucose level was 2.8 mmol/L.

An abdominal ultrasound performed on the second day of life demonstrated enlarged kidneys and pancreas. An echocardiogram demonstrated a 3-mm patent ductus arteriosus, which was successfully closed with indomethacin. A genetics consultation was obtained, and the clinical findings and investigations were noted to be most consistent with Beckwith-Wiedemann syndrome. The differential diagnosis included Perlman's syndrome and Simpson-Golabi-Behmel syndrome.

The child developed hyaline-membrane disease, requiring ventilatory support. She was extubated at 8 days of life but required emergent reintubation for upper-airway obstruction secondary to macroglossia. She was once again extubated at age 17 days but was able to remain extubated on this occasion. However, she did have intermittent airway obstruction, requiring supplemental oxygen and frequent repositioning.

A reduction glossoplasty was performed at age 22 days. A tracheostomy was performed at the outset of the procedure to facilitate airway management. Dexamethasone was used perioperatively (1.5 mg twice daily beginning on the day prior to surgery and continuing until the third postoperative day) to minimize postoperative edema. The tongue measured 7 cm from foramen cecum to tip, and 4.5 cm at its widest part (Fig. 1). A central and vertical tongue reduction was performed (Fig. 2). The tongue was closed in three layers with absorbable suture. Postoperatively, the tongue was able to fit into the oral cavity (Fig. 3). The resected specimen measured 5.3 x 3.5 x 1.0 cm and weighed 9.1 g. Histologic examination demonstrated normal skeletal muscle.

The child began successful oral feeding at 3 weeks postoperatively and required frequent feeds to prevent hypoglycemia. By the third postoperative month, however, the tongue had returned to, and exceeded, its original size (Fig. 4), and the child was no longer able to take oral feeds. She required nasogastric feeding, and subsequently, a gastrostomy feeding tube was placed. The tracheostomy remained in place to prevent upperairway obstruction. Magnetic resonance imaging (MRI) of the oral cavity showed a massively enlarged tongue, the MRI appearance of the tissue being most consistent with muscle, rather than edema or scar tissue.

Discussion

Beckwith-Wiedemann syndrome (BWS) was first described in 1963 by Beckwith,l who reported the autopsy results of three unrelated infants who had died in the neonatal period. In 1964, Wiedemann2 described a familial form of the syndrome. The incidence is estimated at 0.07 per 1000 births, with approximately 15% of cases being familial and the rest sporadic.3

The most consistent finding in BWS is macroglossia, which is present in 82 to 99% of affected individuals.3,4 Other frequent findings include macrosomia (71-87%)34 and abdominal wall abnormalities, including a spectrum of defects ranging from omphalocele to diastasis recti (75-77%).3,4 Other common findings include renal and genitourinary abnormalities (4762%),34 nephromegaly in 23% of individuals,4 earlobe abnormalities, ear creases and posterior helical pits (38-75%),34 and nevus flammeus of the face (3262%).34 Craniofacial anomalies, including midface hypoplasia, prominent occiput, and flat nasal bridge, may be present in approximately 39% of cases.4 Cardiac anomalies are less common in BWS patients, and are seen in 9 to 15% of cases.3,4

Hypoglycemia is present in approximately half of affected individuals and was suspected as a frequent cause of death in an early series reported by Beckwith. It is associated with hyperinsulinemia and may correlate to the hyperplasia of pancreatic islets seen on histologic examination. Unrecognized hypoglycemia, which may persist through the first months of life, may be associated with neurologic damage, which is seen in 9 to 12% of BWS patients.3,4

Figure

Hemihypertrophy is present in 12 to 23% of individuals3,4 and is associated with an increased risk of developing both benign and malignant neoplasms. The most common neoplasms to arise in BWS patients are nephroblastoma, adrenocortical carcinoma, and hepatoblastoma.5 Histologic examination of the kidney demonstrates rests of abnormal nephrogenesis, which may relate to the increased incidence of nephroblastoma. The finding that 7.5% of all BWS patients develop childhood neoplasms, most of which are malignant, should prompt screening with abdominal ultrasound and serum alpha-fetoprotein determinations.5

Chromosomal abnormalities involving the short arm of chromosome 11 have been described in cases of BWS.6 Linkage studies of familial BWS have identified chromosome 11p15 as the locus of the abnormality. The inheritance pattern of familial BWS appears to be autosomal dominant with variable penetrance.

Recent evidence has implicated insulin-like growth factor 2 (IGF-2) in the pathogenesis of BWS. Linkage studies have mapped the gene for IGF2 to chromosome 11p15 and imprinting may be important in regulation of this gene.6,7 Insulin-like growth factor-2 production during normal fetal development is highest in tissues affected by overgrowth in BWS.7

Macroglossia may be a particularly troublesome aspect of BWS, and reduction glossoplasty may be required in about half of patients.8 Macroglossia may present with a spectrum of complications that require intervention. The airway may be compromised at rest, intermittently, related to position, or during feeding. It may cause difficulty feeding, swallowing, and in management of saliva. Older children and adults may have difficulties with speech. The presence of an enlarged tongue may lead to the patient being perceived as mentally impaired. Inability to retract the tongue within the oral cavity can lead to drying, cracking, ulceration, and secondary infection of the tip. Additionally, untreated macroglossia may lead to orofacial maldevelopment with open bite and widening of the dental arches.8-14

Figure 2

The histologic findings in Beckwith-Wiedemann macroglossia have been variously described as showing muscular hyperplasia914 or no abnormality.8

The various techniques of reduction glossoplasty classified by Valcek et al.lo as vertical, central, marginal, anterolateral pedicle, and horizontal filleting. We chose the combined central and vertical technique in the management of our patient to provide reduction in tongue length and width without the complication of an insensate, globular tongue seen with a marginal resection.ll

The macroglossia of Beckwith-Wiedemann syndrome tends to regress with time,5 but up to half of cases require surgery.3 Rimell et al.lS recommend tracheostomy and observation for infants with obstructive macroglossia due to BWS, and later tonsillectomy and adenoidectomy for residual airway obstruction in childhood. Mixter et al.11 obtained good relief of airway obstruction following reduction glossoplasty.

The case presented is unusual in that reduction glossoplasty was performed in the neonatal period. In published series,8,11-14 the age at the time of operation varies from approximately 5 months to early adulthood with good long-term results. We chose to perform surgery in the neonatal period in an attempt to control the airway. Secondary benefits of surgery were felt to include early oral sucking and feeding, with development of normal swallowing reflexes and normal or near-normal speech patterns, improved appearance, and prevention of orthodontic complications.

McManamny et al.8 reported that 3 of 16 patients with BWS macroglossia presenting for tongue reduction required a second operation to adequately reduce the tongue size. This was attributed to an inadequate primary reduction rather than a regrowth of lingual tissue. Kveim et al.14 reported one of three patients requiring a second operative procedure due to "additional growth of the tongue."

The degree of regrowth of the tongue in our patient is unique and may relate to the young age at which she underwent the procedure. There may be persistent overactivity of the Beckwith-Wiedemann growth factors in the early postnatal period, with subsequent diminution at a later age. Sippell et al.16 documented an increased overall growth rate in BWS patients until the age period of 4 to 6 years. After that point, the growth rate fell to approximate the normal population. Weng et al.l7 observed a similar effect and speculated that this was the result of IGF-2 activity being greatest in the youngest BWS patients. Similarly, Chitayat et al.ls documented two cases of BWS with postnatal onset of symptoms, including macroglossia. They observed an increase in the size of the tongue during the first few months of life, and gradual improvement of the condition after 6 months of age.

Our observations of tongue regrowth following reduction glossoplasty in the neonatal period suggests that the optimal management of severe BWS macroglossia should include a period of supportive care, including nutritional support and tracheostomy, if indicated for airway obstruction. It may be beneficial to delay the reduction procedure until such time as the rate of tongue growth decreases, a period of probably at least 6 months.

Figure 3

Figure 4

References

References

1. Beckwith JB. Extreme cytomegaly of the adrenal fetal cortex, omphalocele, hyperplasia of the kidneys and pancreas, and leydig cell hyperplasia-another syndrome? Presented at the annual meeting of Western Society for Pediatric Research, Los Angeles, California, November 11,1963.

2. Wiedemann HR. Complexe malformatif familial l'avec hernie ombilicale et macroglossie, un "syndrome nouveau." J Genet Hum 1964;13:223-232.

References

3. Elliott M, Maher ER. Beckwith-Wiedemann syndrome. J Med Genet 1994; 31:560-564.

4. Sotelo-Avila C, Gonzalez-Crussi F, Fowler JW. Complete and incomplete forms of Beckwith-Wiedemann syndrome: their oncogenic potential. J Pediatr 1980; 96:47-50.

5. Olney AH. Overgrowth syndromes. Pediatr Ann 1990; 19: 119-137.

References

6. Waziri M, Patil SR, Hanson JW, Bartley JA. Abnormality of chromosome 11 in patients with features of BeckwithWiedemann syndrome. J Pediatr 1983; 102:873-876.

7. Hedborg F, Holmgren L, Sandstedt B, Ohlsson R. The cell type-specific IGF2 expression during early human development correlates to the pattern of overgrowth and neoplasia in the Beckwith-Wiedemann syndrome. Am J Pathol 1994; 145:802-817.

8. McManamny DS, Barnett JS. Macroglossia as a presentation of the Beckwith-Wiedemann syndrome. Plast Reconstr Surg 1985; 75:170-176.

References

9. Vogel JE, Mulliken JB, Kaban LB. Macroglossia: a review of the condition and a new classification. Plast Reconstr Surg 1986; 78:715-723.

10. Velcek FT, Klotz DH, Hill CH, et al. Tongue lesions in children. J Pediatr Surg 1979; 14:238-246.

11. Mixter RC, Ewanowski SJ, Carson LV. Central tongue reduction for macroglossia. Plast Reconstr Surg 1993; 91: 1159-1162.

References

12. Morgan WE, Friedman EM, Duncan NO, Sulek M. Surgical management of macroglossia in children. Arch Otolaryngol Head Neck Surg 1996; 122:326-329.

13. Massengill R, Pickrell K. Surgical correction of macroglossia. Pediatrics 1978; 61:485-488.

14. Kveim M, Fisher JC, Jones KL, Gruer B. Early tongue resection for Beckwith-Wiedemann macroglossia. Ann Plast Surg 1985; 14:142-144.

References

15. Rimell FL, Shapiro AM, Shoemaker DL, Kenna MA. Head and neck manifestations of Beckwith-Wiedemann syndrome. Otolaryngol Head Neck Surg 1995; 113:262-265. 16. Sippell WG, Partsch CJ, Wiedemann HR. Growth, bone maturation, and pubertal development in children with the EMG-syndrome. Clin Genet 1989; 35:20-28. 17. Weng EY, Moeschler JB, Graham JM Jr. Longitudinal observations on 15 children with Wiedemann-Beckwith syndrome. Am J Med Genet 1995; 54:366-373. 18. Chitayat D, Rothchild A, Ling E, et al. Apparent postnatal onset of some manifestations of the Wiedemann-Beckwith syndrome. Am J Med Genet 1990; 36:434-439.