There are a number of acquired causes of local gigantism. A body part can attain bigger size from causes as common as the following:

- inflammation, due to trauma or infection

- tumors like osteoid osteoma, melorheostosis, and lipofibromatous hamartoma

- Arteriovenous malformations occurring on a limb, before the closure of epiphyses in long bones

- Elephantiasis, which is quite common in south-east asia due to prevalence of filariasis.

- Still's disease

- amyloidosis

- acromegaly

Congenital causes include:

- Klippel Trenaunay Weber syndrome

- Maffucci syndrome

- macrodystrophia lipomatosa

- neurofibromatosis,

- lipoatrophic diabetes.

- Proteus syndrome, which by one theory accounts for the deformities of the Elephant Man

Assisted reproductive technology (ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. According to the CDC, in general, ART procedures involve surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman. ART has been associated with epigenetic syndromes, specifically BWS and Angelman syndrome. Three groups have shown an increased rate of ART conception in children with BWS. A retrospective case control study from Australia found a 1 in 4000 risk of BWS in their in-vitro population, several times higher than the general population. Another study found that children conceived by in vitro fertilisation (IVF) are three to four times more likely to develop the condition. No specific type of ART has been more closely associated with BWS. The mechanism by which ART produces this effect is still under investigation.

Beckwith–Wiedemann syndrome has an estimated incidence of one in 13,700; about 300 children with BWS are born each year in the United States. The exact incidence of BWS is unknown because of the marked variability in the syndrome's presentation and difficulties with diagnosis. The number of reported infants born with BWS is most likely low because many are born with BWS, but have clinical features that are less prominent and therefore missed. BWS has been documented in a variety of ethnic groups and occurs equally in males and females.

Children conceived through In vitro fertilization have a three to fourfold increased chance of developing Beckwith–Wiedemann syndrome. It is thought that this is due to genes being turned on or off by the IVF procedures.

The birth defect affects men and women equally, and is not limited to any racial group. It is not certain if it is genetic in nature, although testing is ongoing. There is some evidence that it may be associated with a translocation at t(8;14)(q22.3;q13). Some researchers have suggested AGGF1 has an association.

The exact cause of the condition is unknown. There is most evidence to support vascular infarction and ischemic necrosis of salivary gland lobules as a mechanism for the condition. Experimentally, local anaesthetic injections and tying of the arteries is reported to trigger the development of tissue changes similar to NS in lab rats. Factors which are thought to cause this ischemia are listed below, however sometimes there is no evident predisposing factor or initiating event.

- Trauma e.g. during intubation, or surgical procedures

- Local anesthetic injection

- Smoking

- Alcohol

- Diabetes mellitus

- Vascular disease, (e.g. arteriosclerosis)

- Pressure from a dental prosthesis

- Allergy

- Bulimia

- Infection

- Ionizing radiation

Fibrous hamartoma of infancy is a rapidly growing, painless, ill-defined subcutaneous or intradermal nodule that is generally solitary and less than 5 cm in size, though, rarely, multiple lesions occur synchronously.

By 1999, there were 12 reported cases.

The majority of patients are less than 2 years old, with 25% of cases being congenital. Possible locations include the trunk and limbs; usually the upper arm or shoulder. Local excision is the treatment of choice, but it may recur locally.

Macroglossia is uncommon, and usually occurs in children. Macroglossia has been reported to have a positive family history in 6% of cases. The National Organization of Rare Disorders lists macroglossia as a rare disease (less than 200 000 individuals in the US).

Macrocephaly may be pathological, but many people with abnormally large heads or large skulls are healthy. Pathologic macrocephaly may be due to megalencephaly (enlarged brain), hydrocephalus (water on the brain), cranial hyperostosis (bone overgrowth), and other conditions. Pathologic macrocephaly is called "syndromic" when it is associated with any other noteworthy condition, and "nonsyndromic" otherwise. Pathologic macrocephaly can be caused by congenital anatomic abnormalities, genetic conditions, or by environmental events.

Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene, autism, "PTEN" mutations such as Cowden disease, neurofibromatosis type 1, and tuberous sclerosis; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome, Simpson-Golabi-Behmel syndrome (bulldog syndrome), and macrocephaly-capillary malformation (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome, Gorlin Syndrome, (also known as Basal Cell Nevus Syndrome) and cardiofaciocutaneous syndrome; Fragile X syndrome; leukodystrophies (brain white matter degeneration) such as Alexander disease, Canavan disease, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.

At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to schizophrenia and microcephaly.

Environmental events associated with macrocephaly include infection, neonatal intraventricular hemorrhage (bleeding within the infant brain), subdural hematoma (bleeding beneath the outer lining of the brain), subdural effusion (collection of fluid beneath the outer lining of the brain), and arachnoid cysts (cysts on the brain surface).

Gigantism is a rare disorder resulting from increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty. This is most often due to abnormal tumor growths on the pituitary gland. Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.

The prevalence of Klippel–Feil syndrome is unknown due to the fact that there was no study done to determine the true prevalence.

Although the actual occurrence for the KFS syndrome is unknown, it is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.

Perlman syndrome is a rare disease with an estimated incidence of less than 1 in 1,000,000. As of 2008, less than 30 patients had ever been reported in the world literature.

Macroorchidism is a disorder found in males where a subject has abnormally large testes. The condition is commonly inherited in connection with fragile X syndrome, which is also the second most common genetic cause of mental disabilities. The opposite side of the spectrum is called microorchidism, which is the condition of abnormally small testes.

Other possible causes of macroorchidism are long-standing primary hypothyroidism, adrenal remnants in congenital adrenal hyperplasia, follicle stimulating hormone (FSH)-secreting pituitary macroadenomas, local tumors, lymphomas, and aromatase deficiency.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two different substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. The specific mechanisms of these are still not completely understood.

More broadly, GH and IGF have both been identified to be involved most stages of growth: embryonic, prenatal, and postnatal. Moreover, the receptor gene for IGF has been shown to be particularly influential throughout various stages of development, especially prenatally. This is the same for GH receptor genes which have been known to drive overall growth throughout various pathways.

Growth hormone is a precursor (upstream) of IGF-I, but each have their own independent roles in hormonal pathways. Although, both seem to ultimately come together to have a joint effect on growth.

Macrocephaly is a condition in which the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.

Macroglossia may be caused by a wide variety of congenital and acquired conditions. Isolated macroglossia has no determinable cause. The most common causes of tongue enlargement are vascular malformations (e.g. lymphangioma or hemangioma) and muscular hypertrophy (e.g. Beckwith–Wiedemann syndrome or hemihyperplasia). Enlargement due to lymphangioma gives the tongue a pebbly appearance with multiple superficial dilated lymphatic channels. Enlargement due to hemihyperplasia is unilateral. In edentulous persons, a lack of teeth leaves more room for the tongue to expand into laterally, which can create problems with wearing dentures and may cause pseudomacroglossia.

Amyloidosis is an accumulation of insoluble proteins in tissues that impedes normal function. This can be a cause of macroglossia if amyloid is deposited in the tissues of the tongue, which gives it a nodular appearance. Beckwith–Wiedemann syndrome is a rare hereditary condition, which may include other defects such as omphalocele, visceromegaly, gigantism or neonatal hypoglycemia.

The tongue may show a diffuse, smooth generalized enlargement. The face may show maxillary hypoplasia causing relative mandibular prognathism. Apparent macroglossia can also occur in Down syndrome. The tongue has a papillary, fissured surface. Macroglossia may be a sign of hypothyroid disorders.

Other causes include mucopolysaccharidosis, neurofibromatosis, multiple endocrine neoplasia type 2B, myxedema, acromegaly, angioedema, tumors (e.g. carcinoma), Glycogen storage disease type 2, Simpson-Golabi-Behmel syndrome, Triploid Syndrome, trisomy 4p, fucosidosis, alpha-mannosidosis, Klippel-Trenaunay-Weber syndrome, cardiofaciocutaneous syndrome, Ras pathway disorders, transient neonatal diabetes, and lingual thyroid.

Since the syndrome is caused by a genetic mutation in the individual's DNA, a cure is not available. Treatment of the symptoms and management of the syndrome, however, is possible.

Depending on the manifestation, surgery, increased intake of glucose, special education, occupational therapy, speech therapy, and physical therapy are some methods of managing the syndrome and associated symptoms.

The term fibromatosis refers to a group of soft tissue tumors which have certain characteristics in common, including absence of cytologic and clinical malignant features, a histology consistent with proliferation of well-differentiated fibroblasts, an infiltrative growth pattern, and aggressive clinical behavior with frequent local recurrence. It is classed by the World Health Organisation as an intermediate soft tissue tumor related to the sarcoma family.

The heterogeneity of the Klippel–Feil syndrome has made it difficult to outline the diagnosis as well as the prognosis classes for this disease. Because of this, it has complicated the exact explanation of the genetic cause of the syndrome.

The prognosis for most individuals with KFS is good if the disorder is treated early on and appropriately. Activities that can injure the neck should be avoided, as it may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable.

Subtypes of fibromatosis include -

- Juvenile fibromatosis

- Fibromatosis colli: Non-neoplastic sternocleidomastoid muscle enlargement in early infancy. Does not generally require resection and responds well to physiotherapy.

- Infantile digital fibromatosis

- Infantile myofibromatosis

- Ipofibromatosis

- Fibromatosis hyalinica multiplex

- Plantar fibromatosis

- Penile fibromatosis (Peyronie's disease)

- Palmar fibromatosis (Dupuytren's contracture)

The condition is rare.

The typical age range of those affected by the condition is about 23–66 years of age. It usually occurs in smokers. The male to female ratio has been reported as 1.95:1, and 2.31:1.

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".

There is disagreement as to how cases of KTS should be classified if there is an arteriovenous fistula present. Although several authorities have suggested that the term Parkes-Weber syndrome is applied in those cases, ICD-10 currently uses the term "Klippel–Trénaunay–Weber syndrome".

Simpson–Golabi–Behmel syndrome (SGBS), also called Bulldog syndrome, Sara Agers syndrome, Golabi–Rosen syndrome, Simpson dysmorphia syndrome (SDYS) or X-linked dysplasia gigantism syndrome (DGSX), is a rare inherited congenital disorder that can cause craniofacial, skeletal, cardiac, and renal abnormalities.

The syndrome is inherited in an X-linked recessive fashion, where males express the phenotype and females usually do not. Females that possess one copy of the mutation are considered to be carriers of the syndrome and may express varying degrees of the phenotype.

Rud syndrome is a poorly characterized disorder, probably of X-linked recessive inheritance, named after Einar Rud who described 2 patients with the case in 1927 and 1929. It was argued that all reported cases of Rud syndrome are genetically heterogeneous and significantly differ from the original case reports of Rud and that the designation Rud syndrome should be eliminated and that the patients with such diagnosis should be reassigned to other syndromes, such as Refsum disease and Sjögren-Larsson syndrome.Some consider Rud syndrome and Sjögren-Larsson syndrome the same entity and that Rud syndrome doesn't exist.