Dept. of Obstetrics and Gynecology, Karl-Franzens University, Auenbruggerplatz 14, A - 8010 Graz, Austria

Synonyms: Tongue gigantism, enlarged or protruding tongue.

Definition: In children and adults: a resting tongue that protrudes beyond the teeth or alveolar ridge or mandible.

Prevalence: Depends on the underlying disorder (e.g., present in 97.5% of Beckwith-Wiedemann syndrome cases¹: incidence 0.73:10,000 live births², congenital hypothyroidism: incidence 2.5: 10,000 live births³).

Etiology: When isolated it is usually sporadic, except for two families in which an autosomal dominant transmission has been described. Otherwise, depends on the underlying disorder (see Table 1).

Pathogenesis: Depends on the underlying disorder. In this case, sonographic appearance at 27 weeks suggests development at mid-trimester or earlier. In cases of Beckwith-Wiedeman syndrome, it is part of the generalized visceromegaly probably secondary to fetal hyperinsulinism¹ (although it is not present in diabetic fetopathy). This is mediated by elevated hPL levels in chronic hypoglycemia due to hyperplasia of Langerhans" islet cells⁴ or by raised growth factors, especially in familial cases where cytogenetic abnormalities involving bands p13-15 of chromosome 11 can be found (p15-pter) ^5,6,7. Recently uniparental paternal disomy has been shown to be the underlying disorder in some cases of Beckwith-Wiedemann syndrome using 11p15.5 markers⁸- a region that also carries the code for insulin and insulin-like growth hormones⁹.

Diagnosis: Protrusion of the tip of the tongue past an imaginary line drawn on a sagittal scanning plane between the mandible and maxilla (fig 3) or past the lower lip on an axial scan.

Associated anomalies: Depends on the underlying disorder. So far only diagnosed by prenatal ultrasound in cases of Beckwith-Wiedemann syndrome, other features of which include hydramnios (due to impaired fetal swallowing and possibly to increased urine production¹⁰), omphalocele, nephromegaly, gigantism (sometimes hemihypertrophy), hepatomegaly, genital anomalies ^4,10-12, cystic adrenal glands⁴, heart defects¹. In the absence of an omphalocele, a careful search for markers of trisomy 21 is indicated.

Differential diagnosis: See Table 1. Sometimes a biopsy of the tongue is necessary to confirm diagnosis in childhood¹³. If macroglossia is associated with an omphalocele, this is diagnostic of Beckwith-Wiedemann syndrome.

Prognosis: Depends on degree and underlying disorder.

Recurrence risk: Function of the underlying disorder.

Management: Function of the underlying disorder.

MESH: Macroglossia-diagnosis, Beckwith-Wiedemann syndrome, omphalocele. BDE 0618 MIM 153630 ICD9 750.1 CDC 750.120

Address correspondence to Martin C. H. Haeusler, MD, Dept. of Obstetrics and Gynecology, Karl-Franzens University, Auenbruggerplatz 14, A - 8010 Graz, Austria, Ph: 43-316-385-2201, Fax 43-316-385-3061 ¶ From the Department of Pediatric Surgery

Introduction

Macroglossia poses a difficult differential diagnosis. It can be an isolated finding without any pathological significance or can be associated with various syndromes or diseases, which will be summarized in this article. Macroglossia may develop in adults, children or fetuses depending on the etiology. The prenatal diagnosis of macroglossia has been made so far in four cases of Beckwith-Wiedemann syndrome at 28 to 39 weeks gestation^4,10,14,15. We present a fifth case diagnosed at 27 weeks and discuss the definition of macroglossia and the importance of this finding which, in combination with an omphalocele, is diagnostic of Beckwith-Wiedemann syndrome.

Case report

A 34-year-old G₅P₀ had four previous pregnancies, three of which ended in spontaneous abortions at 12, 15, 12 weeks gestation. The other pregnancy resulted in an intrauterine death at 26 weeks, and the fetus showed an omphalocele but no other evidence of the Beckwith-Wiedemann syndrome.

She was referred in this pregnancy at 21 weeks gestation because of a fetal abdominal wall defect. The ultrasound examination⁵¹ showed a singleton fetus with an omphalocele (26 mm in diameter). The biometry was appropriate for gestational age, the amount of amniotic fluid was normal, and no other malformations were evident. Amniocentesis showed a normal female karyotype (46,XX). Amniotic fluid levels of alpha-fetoprotein and acetylcholinesterase were normal. At 25 weeks gestation the mother was admitted because of preeclampsia (Blood pressure: 140/90, increasing proteinuria from 4.7 g/l to 13.3 g/l, raised liver enzymes–gGT 36 U/l, LDH 227 U/l–, uric acid 6.6 mg/100ml).

A repeat ultrasound at 27 weeks showed polyhydramnios; the biparietal diameter, head circumference and femur were just below the 90^th percentile and the diameter of the omphalocele was 38mm (fig.1).

Fig. 2: Left: Midsagittal scan of fetal head at 27 weeks gestation. Arrow indicates macroglossia. Right: Profile of same neonate"s face 4 weeks after birth. Note protruding tongue (arrow).

The diagnosis of Beckwith-Wiedemann syndrome was made based on the combination of macroglossia and an omphalocele.

At 31 weeks a cesarean section was performed because of fetal distress after premature rupture of the membranes. A baby girl was delivered with Apgar scores of 4 and 5 (1 and 5 minutes). She weighed 1540g (50^th percentile¹⁶), and was 380mm long (3^rd percentile¹⁷). Cord blood arterial and venous pH were 7.02 and 7.06, respectively; blood glucose was 46mg/100ml. The neonate was infused with 10% glucose. One hour after delivery, a pediatric surgeon was able to reduce the contents of the omphalocele into the abdominal cavity. Ultrasonography of the kidneys was normal.

The postnatal course was complicated by respiratory distress syndrome, intraventricular hemorrhage grade 1-2, and bowel perforation after meconium ileus, necessitating partial resection of the ileum on the 10^th day. The infant was extubated on the 30^th day. Macroglossia (fig. 2) made feeding difficult so that a nasogastric tube was still being used at the most recent follow-up at 6 months. Neurophysiological development was normal so far and a partial glossectomy may be considered.

Discussion

Definition

Macroglossia is defined, in children and adults, as a resting tongue that protrudes beyond the teeth or alveolar ridge¹⁸ or mandible¹⁹. Overgrowth can involve the tongue and floor of the mouth and can extend to contiguous structures in the neck and oral area²⁰.

Diagnosis

Computed tomography has been used to measure width and structures at the tongue base²¹ such as the hyoglossus and genioglossus muscles. There are no objective measurements throughout pregnancy of normal or abnormal fetal tongue size. This is because it is difficult to define reproducible points on or related to the fetal tongue length. Maximal fetal tongue width can be measured but is of no practical value. Future ultrasound technology will perhaps allow depiction and measurement similar to computed tomography. Until then fetal tongue size can be regarded as normal if, for most of the observation time, the tip of the tongue remains behind a imaginary line drawn on a sagittal scanning plane between the mandible and maxilla (fig. 3) or within the lower lip on an axial scan (fig. 4) and tongue movements are observed. In the four cases reported to date, different degrees of fetal macroglossia were described: increased appearence¹⁰ , subtle protrusion of fetal tongue beyond lips⁴ -similar to fig. 2, or extreme opening of the mouth by protruding tongue^14,15.

Fig. 3: Midsagittal scan of fetal face showing a normal sized tongue (T) not exceeding imaginary line between maxilla and mandible (*) at 27 weeks gestation.

Fig. 4: Axial scan at 27 weeks gestation at the level of the tongue, showing a normal sized tongue (+++), the lip of which is within the lower lip (L). Spine (SP) and pharynx (*) epiglottis between tongue and pharynx.

Differential diagnosis

Table 1 lists the differential diagnosis of neonatal macroglossia and highlights the fact that, to our knowledge, macroglossia was diagnosed prenatally only in cases of Beckwith-Wiedemann syndrome, although the pediatric literature cites several other conditions associated with macroglossia.

Imaging the fetal tongue is crucial in cases of a fetal omphalocele or in fetuses with a family history of Beckwith-Wiedemann syndrome since the interpretation of a sonographically detected omphalocele changes significantly in the presence of macroglossia. Only Beckwith-Wiedemann syndrome is associated with of these two malformations²³. Thus, in contrast with other cases of omphalocele, where there is a significant risk of chromosomal anomalies¹², the procedure-related risk of fetal karyotyping could be avoided in cases of Beckwith-Wiedemann syndrome. The karyotyping could thus be done postnatally, rather than prenatally and include gene imprinting.

A case of isolated fetal macroglossia has hitherto not been reported and would probably need histopathologic evaluation.

Conclusion

There are many causes of congenital macroglossia although, to our knowledge, only four reported cases have been diagnosed prenatally, all as part of the Beckwith-Wiedemann syndrome. Improvement in imaging techniques and heightened awareness of sonographers may lead to earlier prenatal diagnosis even in cases other than Beckwith-Wiedemann syndrome.

Longitudinal studies will be necessary to show at which gestation overgrowth of the fetal tongue may begin, and studies on fetal swallowing may improve our knowledge of the development of hydramnios in cases of macroglossia.

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