Macroglossia in children and adults

An abnormally large or abnormally wide tongue – macroglossia, usually occurs in children and is considered a relatively rare anomaly. Macroglossia usually means a long-term painless enlargement of the tongue. [ 1 ], [ 2 ]

According to ICD-10, it is classified as a congenital malformation of the digestive system with the code Q38.2, although the tongue is also one of the sense organs (since it has taste buds) and part of the articulatory apparatus...

It should be borne in mind that an enlarged tongue may not only be congenital, and in such cases its hypertrophy is classified as an oral disease with the code K14.8.

Doctors may call this pathology differently, dividing it into congenital (true or primary) and acquired (secondary). [ 3 ]

Epidemiology

According to clinical statistics, macroglossia in Beckwith-Wiedemann syndrome occurs in approximately 95% of children with this pathology; while the prevalence of the syndrome itself is estimated at 1 case per 14-15 thousand newborns. And in 47% of children with macroglossia, this syndrome is the basis of the anomaly.

In general, congenital syndromic macroglossia accounts for 24-28% of all cases and approximately the same number for congenital hypothyroidism.

According to some data, 6% of patients have a family history of macroglossia. [ 4 ], [ 5 ]

Causes macroglossia

The most common reasons why macroglossia occurs in newborns (neonatal macroglossia) include:

• Beckwith-Wiedemann syndrome (hemihyperplasia) and Down syndrome;
• primary form of amyloidosis;
• insufficient production of hormones by the thyroid gland - congenital primary hypothyroidism in children, as well as cretinism (cretinism athyreotic) - a rare form of congenital deficiency of thyroid hormones and hypothyroid-muscular hypertrophy (Kocher-Debré-Semillen syndrome);
• malformation of the lymphatic vessels of the tongue - lymphangioma; [ 6 ]
• hemangioma - a benign tumor formed by blood vessels (often occurring in congenital Klippel-Trenaunay-Weber syndrome).

Macroglossia in a child can be observed in genetically determined diseases, primarily in mucopolysaccharidoses type I and type II (Hunter syndrome); hereditary generalized glycogenosis 2 - Pompe disease (with accumulation of glycogen in tissues).

Macroglossia with abnormal jaw development and cleft palate is observed in more than 10% of children with Pierre Robin syndrome. A significantly widened tongue is often protruded in children with Angelman syndrome (associated with the loss of part of the genes on chromosome 15), as well as craniofacial dysostosis - Crouzon syndrome.

In young age, the presence of a hormonally active tumor of the anterior pituitary gland leads to hypersecretion of STH (growth hormone somatotropin) and the development of acromegaly, among the symptoms of which is an increase in the size of the nose, lips, tongue, etc. In old age, the size of the tongue can increase with AL amyloidosis, tooth loss syndrome (edentulism). [ 7 ]

The etiology of macroglossia has also been associated with endocrine and metabolic disorders; myxedema; Hashimoto's autoimmune thyroiditis; neurofibromatosis;multiple myeloma leading to paraamyloidosis (Lubarsh-Pick syndrome); cystic hygroma or thyroglossal duct cyst; rhabdomyosarcoma. [ 8 ], [ 9 ]. Macroglossia may also develop as a side effect in HIV-infected patients taking lopinavir and ritonavir. [ 10 ]

Macroglossia observed in acquired diseases usually occurs due to chronic infectious or inflammatory diseases, malignancies, endocrine disorders and metabolic disorders. These include hypothyroidism, amyloidosis, acromegaly, cretinism, diabetes mellitus and inflammatory conditions such as syphilis, tuberculosis, glossitis, benign and malignant tumors such as lymphoma, neurofibromatosis, allergic reactions, radiation, surgery, polymyositis, head and neck infections, trauma, bleeding, lymphangioma, hemangioma, lipoma, venous congestion etc. [ 11 ]

Risk factors

The above-mentioned pathologies and diseases are factors that increase the risk of tongue enlargement as one of the signs of their clinical manifestation.

The altered gene in dominant genetic abnormalities is inherited from either parent or may be the result of a new mutation. And the risk of passing on the abnormal gene is 50%.

Pathogenesis

The mechanism of development of congenital macroglossia is rooted in hypertrophy of the muscular (striated) tissue of the tongue, which is formed in the fetus at 4-5 weeks of pregnancy from embryonic connective tissue (mesenchyme) of the ventral and medial muscular rudiments (myotomes) at the bottom of the pharynx and the postauricular parts of the gill arches, as well as from myoblasts of the occipital somites (primary segments of the mesoderm). The normal size of the tongue varies and changes with age, with the greatest growth occurring in the first 8 years after birth and reaching full growth at 18 years. [ 12 ]

Beckwith-Wiedemann syndrome is associated with abnormalities of chromosome 11p15.5, encoding the protein IGF2 – insulin-like growth factor 2, which is a mitogen that stimulates cell division. And the pathogenesis of macroglossia in this case is due to increased cell proliferation during the formation of muscle tissue of the tongue. [ 13 ]

Disruption of the metabolism of glycosaminoglycans of the intercellular matrix of tissues due to enzyme deficiency in mucopolysaccharidosis leads to their accumulation, including in the muscles that form the tongue. And in amyloidosis, the pathological change in the size of the tongue is a consequence of the infiltration of its muscle tissue by amyloid, which is synthesized by abnormal plasma cells of the bone marrow and is an amorphous extracellular glycoprotein of fibrous structure.

Symptoms macroglossia

The first signs of macroglossia are an enlarged and/or thickened tongue, which often protrudes from the oral cavity and may have folds and cracks.

Symptoms associated with this pathology manifest themselves in the form of:

• difficulties in feeding infants and difficulties in eating by children and adults;
• dysphagia (swallowing disorders);
• sialorrhea (drooling);
• speech disorders of varying degrees;
• stridor (wheezing);
• snoring and sleep apnea.

Symptoms associated with macroglossia in congenital hypothyroidism, caused by a deficiency of thyroid hormones, may include excess weight and low body temperature, drowsiness, prolonged jaundice, umbilical hernia, muscle dystonia, constipation, and later, delayed teething, hoarseness, and delayed mental and physical development of the child. [ 14 ]

The mongoloid facial type and macroglossia are the external signs of trisomy 21, that is, congenital Down syndrome, which was first described in the middle of the 19th century by the English doctor J. Down, who defined this condition as mongolism. Only in the second half of the last century did the syndrome receive its current name.

An extra copy of chromosome 21 is the cause of a failure of the gene-regulatory mechanism of intrauterine development, causing typical morphological disorders in the formation of the facial part of the skull. Describing the recognizable phenotype of patients with this syndrome, specialists note such common external signs as: orthognathic facial profiling characteristic of representatives of the Mongoloid race (that is, the face is vertically flatter, with a low bridge of the nose), pronounced zygomatic arches, as well as a slightly raised eye shape toward the temporal edge of the superciliary arch.

The tip of the thickened tongue often protrudes from the slightly open mouth, since the abnormal development of the skull bones results in a short upper jaw, which leads to malocclusion and open bite. For this reason, macroglossia in Down syndrome is considered relative, since the tissues of the tongue do not have histological changes.

Complications and consequences

The list of complications and negative consequences of an abnormally enlarged tongue includes:

• ulceration and necrosis of the tissues of the tip of the tongue (and sometimes the oral mucosa);
• maxillofacial anomalies and malocclusion;
• problems with articulation;
• obstruction of the upper respiratory tract (with hypertrophy of the posterior part of the tongue);
• depression and psychological problems.

Diagnostics macroglossia

Traditionally, diagnosis begins with a thorough history, physical examination, and comparison of all presenting symptoms to identify the cause of the enlarged tongue.

It should be borne in mind that many healthy newborns stick out their tongues above the edges of the gums and between the lips, and this is typical of their stage of development, because the tongue of a baby in the first months of life is quite wide and occupies the entire oral cavity, touching the gums and pads on the inner surfaces of the cheeks (which is physiologically determined - the need for sucking).

Laboratory tests may include tests for serum STH levels, thyroid hormones, including thyroid stimulating hormone in the blood of newborns (test for congenital hypothyroidism ), urine glycosaminoglycans (GAG), etc.

The following are carried out:

• thyroid gland research,
• genetic research.

Instrumental diagnostics are used to visualize the facial part of the skull (X-ray), as well as to examine the tongue (ultrasound, computed tomography and magnetic resonance imaging).

During antenatal diagnostics (ultrasound screening of pregnant women), macroglossia in the fetus can be detected by ultrasound - if visualization techniques in the appropriate planes are used during the ultrasound examination. [ 15 ]

Differential diagnosis

Differential diagnostics is designed to distinguish macroglossia from acute angioedema or swelling of the tongue in gastrointestinal diseases and diabetes, as well as its inflammation (glossitis).

Treatment macroglossia

Treatment depends on the underlying cause and severity. In mild cases, correction of articulation disorders by a speech therapist and bite disorders by an orthodontist may be sufficient.

Only surgical treatment can reduce the tongue: an operation is performed – partial glossectomy (most often, wedge-shaped), which not only improves the appearance, but also optimizes the functions of the tongue. [ 16 ]

In addition, if possible, it is necessary to treat the diseases that caused the enlargement of the tongue. [ 17 ]

Prevention

Preventive measures for this pathology have not been developed, but before planning a pregnancy, it is advisable to consult a geneticist if there were congenital anomalies in the family.

Forecast

The underlying cause and severity of the symptoms macroglossia causes determines its prognosis. Unfortunately, in congenital disorders, the prognosis is poor. In most cases, the clinical course is usually favorable. In patients with complications, interventions should be considered to improve clinical outcomes. The prognosis ultimately depends on the severity, underlying etiology, and success of treatment.