Although it may be asymptomatic, symptoms usually are more likely to be present and more severe with larger tongue enlargements. Signs and symptoms include:

- Dyspnea - difficult, noisy breathing, obstructive sleep apnea or airway obstruction

- Dysphagia - difficulty swallowing and eating

- Dysphonia - disrupted speech, possibly manifest as lisping

- Sialorrhea - drooling

- Angular cheilitis - sores at the corners of the mouth

- Crenated tongue - indentations on the lateral borders of the tongue caused by pressure from teeth ("pie crust tongue")

- Open bite malocclusion - a type of malocclusion of the teeth

- Mandibular prognathism - enlarged mandible

- Mouth breathing

- Orthodontic abnormalities - including diastema and tooth spacing

A tongue that constantly protrudes from the mouth is vulnerable to drying out, ulceration, infection or even necrosis.

The ICD-10 lists macroglossia under "other congenital malformations of the digestive system". Definitions of macroglossia have been proposed, including "a tongue that protrudes beyond the teeth during [the] resting posture" and "if there is an impression of a tooth on the lingual border when the patients slightly open their mouths". Others have suggested there is no objective definition of what constitutes macroglossia. Some propose a distinction between "true macroglossia", when histologic abnormalities correlate with the clinical findings of tongue enlargement, and "relative macroglossia", where histology does not provide a pathologic explanation for the enlargement. Common examples of true macroglossia are vascular malformations, muscular enlargement and tumors; whilst Down syndrome is an example of relative macroglossia. "Pseudomacryglossia" refers to a tongue that is of normal size but gives a false impression of being too large in relation to adjacent anatomical structures. The Myer classification subdivides macroglossia into generalized or localized.

Examples of congenital disorders which affect the tongue include:

- Aglossia - complete absence of the tongue at birth

- Ankyloglossia (tongue tie) - where the lingual frenum tethers the tongue to the floor of the mouth. If it interferes with oral hygiene and feeding, frenectomy may be indicated.

- Hypoglossia - congenitally short tongue

- Microglossia

- Macroglossia - an abnormally large tongue, seen in some disorders such as Down syndrome (although macroglossia can be an acquired condition as well).

- Hamartomata - for example Leiomyomatous hamartoma

- Glossoptosis

- Choristomata - For example, osseous choristoma of the tongue, a very rare condition characterized by a nodule on the dorsum of the tongue containing mature lamellar bone without osteoblastic or osteoclastic activity. Cartilagenous (chondroid), and glial choristomas may also very rarely occur on the tongue.

- Lingual thyroid

- Cleft tongue (bifid tongue) - completely cleft tongue is a rare condition caused by a failure of the lateral lingual swellings to merge. More common is an incompletely cleft tongue, appearing as midline fissure. This is normally classed as fissured tongue.

Tongue diseases can be congenital or acquired, and are multiple in number. Considered according to a surgical sieve, some example conditions which can involve the tongue are discussed below. Glossitis is a general term for tongue inflammation, which can have various etiologies, e.g. infection.

Crenated tongue (also called scalloped tongue, pie crust tongue, lingua indentata, or crenulated tongue) is a descriptive term for the appearance of the tongue when there are indentations along the lateral borders (the sides), as the result of compression of the tongue against the adjacent teeth.

The oral mucosa in the area of crenation is usually of normal color, but there may be erythema (redness) if exposed to a high degree of friction or pressure. Crenated tongue is usually asymptomatic and harmless.

It is not a disease as such, but usually results from habits where the tongue is pressed against the lingual surfaces (the side facing the tongue) of the dental arches, or from any cause of macroglossia (enlarged tongue), which in itself has many causes such as Down syndrome.

Where crenation is caused by parafunctional habits, there may also be associated bruxism, linea alba, or morsicatio buccarum.

Beckwith–Wiedemann syndrome (; abbreviated BWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features.

Common features used to define BWS are:

- macroglossia (large tongue),

- macrosomia (above average birth weight and length),

- microcephaly

- midline abdominal wall defects (omphalocele/exomphalos, umbilical hernia, diastasis recti),

- ear creases or ear pits,

- neonatal hypoglycemia (low blood sugar after birth).

- Hepatoblastoma

Dental open bite occurs in patients where the anterior teeth fail to touch. However, this is not accompanied by the skeletal tendency of having an open bite. Thus this type of open bite may happen in patients who have horizontal or hypodivergent growth pattern. These patients have normal jaw growth and do not have the long face syndrome. The anterior open bite in these patients may be caused by Macroglossia, Tongue thrusting habit or digit sucking habits. Some of the characteristics of a dental open bite include:

- Normal lower anterior facial height

- Horizontal/Hypodivergent growth pattern

- Occlusal plane diverges after the premolar contact

- Under-eruption of the anterior incisors

- Over-eruption of the posterior incisors

- Proclined upper and lower incisors

- No vertical maxillary excess or gummy smile

- Presence of habits such as thumb sucking, tongue thrusting

- Spacing between anterior incisors due to their proclination

Most children with BWS do not have all of these five features. In addition, some children with BWS have other findings including: nevus flammeus, prominent occiput, midface hypoplasia, hemihypertrophy, genitourinary anomalies (enlarged kidneys), cardiac anomalies, musculoskeletal abnormalities, and hearing loss. Also, some premature newborns with BWS do not have macroglossia until closer to their anticipated delivery date.

Given the variation among individuals with BWS and the lack of a simple diagnostic test, identifying BWS can be difficult. In an attempt to standardize the classification of BWS, DeBaun et al. have defined a child as having BWS if the child has been diagnosed by a physician as having BWS and if the child has at least two of the five common features associated with BWS (macroglossia, macrosomia, midline abdominal wall defects, ear creases/ear pits, neonatal hypoglycemia). Another definition presented by Elliot et al. includes the presence of either three major features (anterior abdominal wall defect, macroglossia, or prepostnatal overgrowth) or two major plus three minor findings (ear pits, nevus flammeus, neonatal hypoglycemia, nephromegaly, or hemihyperplasia).

While most children with BWS do not develop cancer, children with BWS do have a significantly increased risk of cancer. Children with BWS are most at risk during early childhood and should receive cancer screening during this time.

In general, children with BWS do very well and grow up to become adults of normal size and intelligence, usually without the syndromic features of their childhood.

Patient with skeletal open bites that accompany dental open bites may have Adenoid faces or Long face syndrome. They are said to have what is known as "Hyperdivergent Growth Pattern" which includes characteristics such as:

- Increased Lower Anterior Facial Height

- Occlusal plane diverges after the 1st molar contact

- May accompany dental open bite

- Narrow nostrils with upturned nose

- Dolicofacial or Leptoprosopic face pattern

- Constricted maxillary arch

- Bilateral Posterior Crossbite

- High and narrow palatal vault

- Presence of crowding in teeth

- Mentalis muscle strain upon forcibly closing of lips

- Possible gummy smile with increased interlabial gap

Cephalometric analysis features of skeletal open bite may include:

- Increased Frankfurt-Mandibular Plane angle

- Steep Occlusal Plane Angle

- Increased SN-MP Angle

- Short Mandibular ramus

- Increased mandibular body length

- Downward and backward position of mandible

- Increased gonial angle

- Proclined upper incisors, retroclined or upright lower incisors

- Posterior part of maxilla is tipped downwards

- Posterior facial height equals 1/2 of anterior facial height

- Increased hard tissue Lower Anterior Facial Height

- Increased total anterior facial height

- Short mandibular ramus

Viken Sassouni developed Sassouni analysis which indicates that patient's with long face syndrome have 4 of their bony planes (mandibular plane, occlusal plane, palatal plane, SN plane) steep to each other.

Factors that can contribute to tongue thrusting include macroglossia (enlarged tongue), thumb sucking, large tonsils, hereditary factors, ankyloglossia (tongue tie), and certain types of artificial nipples used in feeding infants, also allergies or nasal congestion can cause the tongue to lie low in the mouth because of breathing obstruction and finally contributing to tongue thrusting. In addition, it is also seen after prolonged therapy by levodopa in Parkinsonism, also it occurs as extra pyramidal side effect (Acute muscular dystonia) after use of Neuroleptics (Anti-Psychotics).

Tongue thrust (also called reverse swallow or immature swallow) is the common name of orofacial muscular imbalance, a human behavioral pattern in which the tongue protrudes through the anterior incisors during swallowing, speech, and while the tongue is at rest. Nearly all infants exhibit a swallowing pattern involving tongue protrusion, but by six months of age most lose this reflex allowing for the ingestion of solid foods.

Since 1958, the term "tongue thrust" has been described and discussed in speech and dental publications by many writers. Many school-age children have tongue thrust. For example, according to recent literature, as many as 67–95 percent of children 5–8 years old exhibit tongue thrust, which may be associated with or contributing to an orthodontic or speech problem. Up to the age of four, there is a possibility that the child will outgrow tongue thrust. However, if the tongue thrust swallowing pattern is retained beyond that age, it may be strengthened.

In traditional Chinese medicine, scalloping of the tongue is said to indicate qi vacuity. In some homeopathic sources, scalloping of the tongue is said to be indicative of high blood pressure.

Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem: excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, exaggerated jaundice, and low body temperature. If fetal deficiency was severe because of complete absence (athyreosis) of the gland, physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue (macroglossia).

In the era before newborn screening, less than half of cases of severe hypothyroidism were recognized in the first month of life. As the months proceeded, these babies would grow poorly and be delayed in their development. By several years of age, they would display the recognizable facial and body features of cretinism. Persistence of severe, untreated hypothyroidism resulted in severe mental impairment, with an IQ below 80 in the majority. Most of these children eventually ended up in institutional care.

Characteristics include varying degrees of developmental disability, epilepsy, hypotonia, and both hypopigmentation and hyperpigmentation. Patients also exhibit a distinctive facial structure, characterized by high foreheads, sparse hair on the temple, a wide space between the eyes, epicanthal folds, and a flat nose. Vision and hearing impairments may occur. Patients may also exhibit congenital heart defects, gastroesophageal reflux, cataracts, and supernumerary nipples. Diaphragm problems seen in newborns can lead to death shortly after birth.

- As patients pass into adolescence, the syndrome is characterized by a coarse and flat face, macroglossia, prognathism, inverted lower lip, and psychomotor retardation with muscular hypertonia and contractures.

Around the world, the most common cause of congenital hypothyroidism is iodine deficiency, but in most of the developed world and areas of adequate environmental iodine, cases are due to a combination of known and unknown causes. Most commonly there is a defect of development of the thyroid gland itself, resulting in an absent (athyreosis) or underdeveloped (hypoplastic) gland. A hypoplastic gland may develop higher in the neck or even in the back of the tongue. A gland in the wrong place is referred to as "ectopic", and an ectopic gland at the base or back of the tongue is a "lingual" thyroid. Some of these cases of developmentally abnormal glands result from genetic defects, and some are "sporadic," with no identifiable cause. One Japanese study found a statistical correlation between certain organochlorine insecticides and dioxin-like chemicals in the milk of mothers who had given birth to infants with congenital hypothyroidism.

In some instances, hypothyroidism detected by screening may be transient. One common cause of this is the presence of maternal antibodies that temporarily impair thyroid function for several weeks.

Cretinism is an old term for the state of mental and physical retardation resulting from untreated congenital hypothyroidism, usually due to iodine deficiency from birth because of low iodine levels in the soil and local food sources. The term, like so many other 19th century medical terms, acquired pejorative connotations as it became used in lay speech. It is now rarely used by physicians.

It is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. ICF syndrome patients exhibit facial anomalies which include hypertelorism, low-set ears, epicanthal folds and macroglossia.

Pallister–Killian syndrome (also tetrasomy 12p mosaicism or Pallister mosaic aneuploidy syndrome) is an extremely rare genetic disorder occurring in humans. Pallister-Killian occurs due to the presence of the anomalous extra isochromosome 12p, the short arm of the twelfth chromosome. This leads to the development of tetrasomy 12p. Because not all cells have the extra isochromosome, Pallister-Killian is a mosaic condition (more readily detected in skin fibroblasts).

It was first described by Philip Pallister in 1977 and further researched by Maria Teschler-Nicola and Wolfgang Killian in 1981.

ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare autosomal recessive immune disorder.

Features that result from high level of GH or expanding tumor include:

- Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin

- Soft tissue swelling of internal organs, notably the heart with attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech

- Generalized expansion of the skull at the fontanelle

- Pronounced brow protrusion, often with ocular distension (frontal bossing)

- Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing

- Hypertrichosis, hyperpigmentation and hyperhidrosis may occur in these patients.

- Acrochordon (skin tags)

- Carpal tunnel syndrome

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.

Angular cheilitis is a fairly non specific term which describes the presence of an inflammatory lesion in a particular anatomic site (i.e. the corner of the mouth). As there are different possible causes and contributing factors from one person to the next, the appearance of the lesion is somewhat variable. The lesions are more commonly symmetrically present on both sides of the mouth, but sometimes only one side may be affected. In some cases, the lesion may be confined to the mucosa of the lips, and in other cases the lesion may extend past the vermilion border (the edge where the lining on the lips becomes the skin on the face) onto the facial skin. Initially, the corners of the mouth develop a gray-white thickening and adjacent erythema (redness). Later, the usual appearance is a roughly triangular area of erythema, edema (swelling) and breakdown of skin at either corner of the mouth. The mucosa of the lip may become fissured (cracked), crusted, ulcerated or atrophied. There is not usually any bleeding. Where the skin is involved, there may be radiating rhagades (linear fissures) from the corner of the mouth. Infrequently, the dermatitis (which may resemble eczema) can extend from the corner of the mouth to the skin of the cheek or chin. If "Staphylococcus aureus" is involved, the lesion may show golden yellow crusts. In chronic angular cheilitis, there may be suppuration (pus formation), exfoliation (scaling) and formation of granulation tissue.

Sometimes contributing factors can be readily seen, such as loss of lower face height from poorly made or worn dentures, which results in mandibular overclosure ("collapse of jaws"). If there is a nutritional deficiency underlying the condition, various other signs and symptoms such as glossitis (swollen tongue) may be present. In people with angular cheilitis who wear dentures, often there may be erythematous mucosa underneath the denture (normally the upper denture), an appearance consistent with denture-related stomatitis. Typically the lesions give symptoms of soreness, pain, pruritus (itching) or burning or a raw feeling.

Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait.

About half of affected patients develop cherry-red spots in the eye.

Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia.

- Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate.

- Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis.

- Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some

- Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia

- Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure

- Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. *Dysostosis multiplex (as in the mucopolysaccharidoses)

- 10–80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10-fold elevated (20–50-fold increased in viscera)

- Galactose-containing oligosacchariduria and moderate keratan sulfaturia

- Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4).

Several different nutritional deficiency states of vitamins or minerals have been linked to AC. It is thought that in about 25% of people with AC, iron deficiency or deficiency of B vitamins are involved. Nutritional deficiencies may be a more common cause of AC in Third World countries. Chronic iron deficiency may also cause koilonychia (spoon shaped deformity of the fingernails) and glossitis (inflammation of the tongue). It is not completely understood how iron deficiency causes AC, but it is known that it causes a degree of immunocompromise (decreased efficiency of the immune system) which may in turn allow an opportunistic infection of candida. Vitamin B2 deficiency (ariboflavinosis) may also cause AC, and other conditions such as redness of mucous membranes, magenta colored glossitis (pink inflammation of the tongue). Vitamin B5 deficiency may also cause AC, along with glossitis, and skin changes similar to seborrhoeic dermatitis around the eyes, nose and mouth. Vitamin B12 deficiency is sometimes responsible for AC, and commonly occurs together with folate deficiency (a lack of folic acid), which also causes glossitis and megaloblastic anemia. Vitamin B3 deficiency (pellagra) is another possible cause, and in which other association conditions such as dermatitis, diarrhea, dementia and glossitis can occur. Biotin (vitamin B7) deficiency has also been reported to cause AC, along with hair loss (alopecia) and dry eyes. Zinc deficiency is known to cause AC. Other symptoms may include diarrhea, alopecia and dermatitis. Acrodermatitis enteropathica is an autosomal recessive genetic disorder causing impaired absorption of zinc, and is associated with AC.

In general, these nutritional disorders may be caused by malnutrition, such as may occur in alcoholism or in poorly considered diets, or by malabsorption secondary to gastrointestinal disorders (e.g. Coeliac disease or chronic pancreatitis) or gastrointestinal surgeries (e.g. pernicious anemia caused by ileal resection in Crohn's disease).

Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

Acromegaly is typically due to the pituitary gland producing too much growth hormone. In more than 95% of cases the excess production is due to a benign tumor, known as a pituitary adenoma. The condition is not inherited from a person's parents. Rarely acromegaly is due to tumors in other parts of the body. Diagnosis is by measuring growth hormone after a person has drunk glucose or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to look for an adenoma. If excess growth hormone is produced during childhood the result is gigantism.

Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the preferred treatment and is most effective when the tumor is smaller. In those in whom surgery is not effective, medications of the somatostatin analogue or GH receptor antagonist type may be used. The effects of radiation therapy are more gradual than that of surgery or medication. Without treatment those affected live on average 10 years less; however, with treatment life expectancy is typically normal.

Acromegaly affects about 6 per 100,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. The first medical description of the disorder occurred in 1772 by Nicolas Saucerotte. The term is from Greek "akron" meaning "extremity" and "mega" meaning "large".

Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size (macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (called myoclonus) and have red spots in their eyes (cherry red spots). They are often unable to coordinate voluntary movement (called ataxia). Tremors, impaired vision, and seizures also occur in children with ML I. Tests reveal abnormal enlargement of the liver (hepatomegaly) and spleen (splenomegaly) and extreme abdominal swelling. Infants with ML I generally lack muscle tone (hypotonia) and have mental retardation that is either initially or progressively severe. Many patients suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before the age of 1 year.