Macroglossia in children and adults

A disproportionately large or abnormally wide tongue - macroglossia, as a rule, occurs in children and is considered a fairly rare anomaly. Macroglossia usually means prolonged 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 the enlargement of the tongue can be not only congenital, and in such cases its hypertrophy is attributed to diseases of the oral cavity with the code K14.8.

Doctors can call this pathology differently with a division into congenital (true or primary) and acquired (secondary). [3]

Epidemiology

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

And in general, congenital syndromic macroglossia accounts for 24-28% of all cases, and about the same - for congenital hypothyroidism.

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

Causes macroglossia

The most common causes of macroglossia in newborns (neonatal macroglossia) include:

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

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

Macroglossia against the background of abnormal development of the jaws and cleft palate is observed in more than 10% of children with  Pierre Robin's syndrome . Often, a significantly dilated tongue is sticking out in children with  Angelman's syndrome  (associated with the loss of some genes on chromosome 15), as well as craniofacial dysostosis -  Cruson's syndrome .

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

The etiology of macroglossia is also associated with endocrine and metabolic disorders; myxedema ; Hashimoto's autoimmune thyroiditis; neurofibromatosis ; leading to paraamyloidosis (Lubarsh-Pick syndrome)  multiple myeloma ; cystic hygroma or cyst of the thyroid-lingual duct; rhabdomyosarcoma . [8], [9]... Macroglossia can 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, malignant neoplasms, 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 pathologies and diseases listed above are factors that increase the risk of tongue enlargement as one of the signs of their clinical manifestation.

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

Pathogenesis

The mechanism of development of congenital macroglossia lies in the hypertrophy of the muscle (striated) tissue of the tongue formed in the fetus at 4-5 weeks of gestation from the embryonic connective tissue (mesenchyme) of the ventral and medial muscle rudiments (myotomes) at the bottom of the pharynx and behind the ear of the branchial arches, as well as 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 of age.[12]

Beckwith-Wiedemann syndrome is associated with abnormalities of chromosome 11p15.5, which encodes the IGF2 protein, insulin-like growth factor 2, which belongs to mitogens that stimulate cell division. And the pathogenesis of macroglossia in this case is due to increased cell proliferation during the formation of the 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, a pathological change in the size of the tongue is a consequence of the infiltration of its muscle tissue with amyloid, which is synthesized by abnormal plasma cells of the bone marrow and is an amorphous extracellular glycoprotein of a fibrous structure. 

Symptoms macroglossia

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

Symptoms associated with this pathology appear as:

• Difficulty feeding babies and difficulty eating for children and adults
• dysphagia (swallowing disorders);
• sialorrhea (salivation);
• speech disorders of varying degrees;
• stridor (wheezing);
• snoring and sleep apnea.

Symptoms caused by a deficiency of thyroid hormones, which are accompanied by macroglossia in congenital hypothyroidism, can manifest themselves as overweight and low body temperature, drowsiness, prolonged jaundice, umbilical hernia, muscular dystonia, constipation, and later - delayed teething, hoarseness and physical delay child development. [14]

Mongoloid face type and macroglossia are external signs of trisomy 21, that is, congenital  Down syndrome , which was first described by the English physician J. Down in the middle of the 19th century, who defined this condition as Mongolism. Only in the second half of the last century, the syndrome received its current name.

An extra copy of chromosome 21 is the cause of the failure of the gene-regulatory mechanism of intrauterine development, which causes typical morphological disorders in the formation of the facial part of the skull. Describing the recognizable phenotype of patients with this syndrome, experts note such general external signs as: orthognathic facial profiling characteristic 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 to the temporal edge of the superciliary arc section of the eyes.

The tip of the thickened tongue is often poked out of the parted mouth, since the upper jaw is short due to the abnormal development of the bones of the skull, which leads to a violation of the occlusion and an open bite. Because of this, 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 of the oral mucosa);
• maxillofacial anomalies and malocclusion;
• problems with articulation;
• obstruction of the upper airways (with hypertrophy of the back of the tongue);
• depression and psychological problems.

Diagnostics macroglossia

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

It should be borne in mind that many healthy newborns protrude the tongue above the edges of the gums and between the lips, and this is characteristic of their stage of development, because the tongue in an infant in the first months of life is wide enough and occupies the oral cavity completely, touching the gums and pads on the inner surfaces of the cheeks ( which is due physiologically - the need for sucking).

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

Are carried out:

• studies of the thyroid gland ,
• genetic research .

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

In the course of antenatal diagnostics (with ultrasonographic screening of pregnant women), macroglossia in the fetus can be detected by ultrasound - if imaging techniques in the appropriate planes are used during it. [15]

Differential diagnosis

Differential diagnosis is intended to distinguish macroglossia from acute angioedema or swelling of the tongue in diseases of the gastrointestinal tract 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 malocclusion by an orthodontist may be sufficient.

And only surgical treatment can reduce the tongue: an operation is performed - a partial glosssectomy (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 increase in the size of the tongue. [17]

Prevention

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

Forecast

The prognosis also depends on the underlying cause and severity of the symptoms that macroglossia causes. Unfortunately, congenital diseases are disappointing. 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 the treatment.