Amastia refers to a rare clinical anomaly in which both internal

breast tissue The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

and the visible

nipple The nipple is a raised region of tissue on the surface of the breast from which, in females, milk leaves the breast through the lactiferous ducts to feed an infant. The milk can flow through the nipple passively or it can be ejected by smooth mu ...

are absent on one or both sides. It affects both men and women. Amastia can be either isolated (the only medical condition) or

comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary c ...

with other syndromes, such as

ectodermal dysplasia Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Sau ...

Syndactyly Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, ''syn'' 'together' and δάκ� ...

(

Poland's syndrome Poland syndrome is a birth defect characterized by an underdeveloped chest muscle and short webbed fingers on one side of the body. There may also be short ribs, less fat, and breast and nipple abnormalities on the same side of the body. Typical ...

) and

lipoatrophic diabetes Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes. See also * Familial partial lipodystrophy * Congenital generalized lipodystrophy Congenital generalized li ...

. This abnormality can be classified into various types, and each could result from different pathologies. Amastia differs from

amazia Amazia refers to a condition where one or both of the mammary glands is absent (the nipple and areola remain present). This may occur either congenitally or iatrogenically (typically the result of surgical removal and/or radiation therapy). Amaz ...

and athelia. ''Amazia'' is the absence of one or both mammary glands but the nipples remain present, and ''athelia'' is the absence of one or both nipples, but the mammary gland remains. Amastia is presumably due to failure of embryologic (before birth)

mammary ridge The mammary ridge or mammary crest is a primordium specific for the development of mammary glands. Development The mammary ridge is primordial for the mammary glands on the chest in humans, and is associated with mammary gland and breast developm ...

development or incomplete

involution Involution may refer to: * Involute, a construction in the differential geometry of curves * '' Agricultural Involution: The Processes of Ecological Change in Indonesia'', a 1963 study of intensification of production through increased labour inpu ...

. People with amastia often suffer from ectodermal defects, which include various syndromes such as

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...

, isolated

pectoral muscle Pectoral muscles (colloquially referred to as "pecs") are the muscles that connect the front of the human chest with the bones of the upper arm and shoulder. This region contains four muscles that provide movements to the upper limbs or ribs. P ...

and abnormal formation of the arms. Treatment for female amastia particularly includes psychological guidance and

breast reconstruction Breast reconstruction is the surgical process of rebuilding the shape and look of a breast, most commonly in women who have had surgery to treat breast cancer. It involves using autologous tissue, prosthetic implants, or a combination of both wit ...

. Because there is no breast tissue, breastfeeding is not possible. If amastia only appears on one side, then it is possible to breastfeed on the other side. Often, people with amastia decide against treatment.

Classification

Amastia can be either

iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 2 ...

or congenital. The congenital amastia are further divided into syndromic type and non-syndromic type respectively. As the definition suggests, syndromic amastia is often associated with obvious symptoms. The common case is

hypoplasia Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ. Unilateral amastia is less common than bilateral amastia. Almost all the non-syndromic amastia patients are female.

Signs and symptoms

Typically, amastia patients have both their

and

areola The human areola (''areola mammae'', or ) is the pigmented area on the breast around the nipple. Areola, more generally, is a small circular area on the body with a different histology from the surrounding tissue, or other small circular ar ...

missing, and the nipple may be absent on one or both sides of the breasts. Abnormalities are not often associated with the breasts. However, symptoms such as

hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...

, saddle nose, cleft palate, urologic disorders and dysfunction of muscle, upper and lower limb have been observed. Sometimes several members of a family can be diagnosed as amastia simultaneously, all of them are carriers of mutations in

TBX3 T-box transcription factor TBX3 is a protein that in humans is encoded by the ''TBX3'' gene. T-box 3 (TBX3) is a member of the T-box gene family of transcription factors which all share a highly conserved DNA binding domain known as the T-box. The ...

gene. This mutation could cause various abnormalities, not only amastia, but also deformation of limb and teeth. Cases of unilateral amastia are uncommon, and they are often associated with hypoplasia of pectoral major muscle and/or the thorax. Bilateral amastia is more common because it is often associated with other different syndromes. Therefore, the symptoms of bilateral amastia are easier to be diagnosed. Various associated syndromes are listed below.

Associated syndromes

Amastia, particularly if it is bilateral, often related to various syndromes, including ectodermal dysplasia and Poland's syndrome, which is characterised by anomalies of underlying

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

and abnormal pectoral muscle respectively. Other syndromes, such as FIG4 associated Yunis Varon syndrome (MIM 216340), acro-der-mato-ungual-lacrimal-tooth (ADULT) syndrome, TP63 associated limb mammary syndrome (MIM 603543), TBX3 associated ulnar syndrome (MIM 181450) and KCTD1 associated scalp-ear-nipple syndrome (MIM 181270) have also been clinically observed.

Ectodermal dysplasia

Ectodermal dysplasia Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Sau ...

is commonly associated with syndromic amastia. The symptoms of ectodermal dysplasia can be referred to abnormal development of several ectodermal-derived structure such as hair, teeth, nails and sweat glands. Other symptoms may include the inability to sweat, vision or hearing loss, missing or underdeveloped fingers or toes and maldevelopment of breast tissue. Genetic mutations may cause ectodermal dysplasia, and these genes can pass from parents to children. The most common case is the mutation of EDA1 gene which is in X chromosome, and this mutation results in X-linked form hypohidrotic ectodermal dysplasia (XLHED). There is strong association between amastia and XLHED. Over 30% male patients with XLHED have absent nipples. 79% female carriers decrease the ability of breastfeeding. This suggests people with amastia should have a comprehensive skin test to exclude this syndrome.

Poland's syndrome

is a genetic disorder associated with abnormal breast development. The prevalence rate of this syndrome is approximately 1 in 20000 to 30000. Both chest wall and upper limb lost normal function, and this syndrome usually occurs unilaterally. Mild and partial forms of Poland's syndrome are common, which often been undiagnosed because the clinical feature is only breast asymmetry and a horizontal anterior axillary fold, without severe symptoms. Other abnormalities include deformation of ribs, absence of pectoralis muscle, hypoplasia or abnormalities of breast and subcutaneous tissue. Patients may also have webbed fingers on one hand, short bones in the forearm or sparse underarm hair.

Al Awadi/Raas-Rothschild syndrome

Al Awadi/Raas-Rothschild syndrome is a rare genetic disorder. Symptoms are often associated with absence or maldevelopment of skeletal part of limbs.

Scalp-ear-nipple syndrome

As the name suggests, Scalp-ear-nipple syndrome is characterized by congenital absence of skin, abnormalities of scalp, malformation of ear structures, and undeveloped nipples.

Mechanism

Mammary glands A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in prima ...

are arranged in breasts of the primates to produce milk for feeding offspring. They are enlarged and modified sweat glands. In the embryological development, mammary glands firstly appear after six weeks of pregnancy in the form of ectodermal ridges. The ectodermal ridge grows thicker and compresses to form mesoderm. As the proliferation persists, mesodermal layer continues to form clusters. The clusters grow and become lobules. At the same time, the clusters also form a pit, which protrudes to generate the nipples. Impairment in some of these processes may cause aplasia of the breast tissue, which may result in amastia. For example, in normal condition,

(milk line) would extend from the bilateral axillary tail to the inguinal region. If this extension does not occur in normal way, the breast would not develop successfully. Amastia may also be caused by the inability of producing parathyroid hormone related protein. The absence of this protein will disrupt the normal development of mammary gland. Therefore, when amastia patients receive medical ultrasound examination, asymmetry or disproportioned mammary tissue may be found.

Causes

Unilateral amastia is usually caused by Poland's syndrome, which is characterized by one side absence of breast. The absence or dysfunction of pectoralis muscle and ribs are common case. It can also be part of other syndromes as described in the previous contents. Other causes may include intra-uterine exposure to teratogenic drugs such as

Dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...

and methimazole /

carbimazole Carbimazole (brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodina ...

treatment during first trimester. For bilateral amastia, the cause has not been well understood so far. It may be related to gene mutation since often patients with bilateral amastia are diagnosed as autosomal dominant and recessive inheritance. Decreasing blood flow in the

subclavian artery In human anatomy, the subclavian arteries are paired major arteries of the upper thorax, below the clavicle. They receive blood from the aortic arch. The left subclavian artery supplies blood to the left arm and the right subclavian artery supplie ...

may also be a cause of amastia. Amastia can also be caused by injuries. These injuries may happen when patients receive surgery, such as

thoracotomy A thoracotomy is a surgical procedure to gain access into the pleural space of the chest. It is performed by surgeons (emergency physicians or paramedics under certain circumstances) to gain access to the thoracic organs, most commonly the hea ...

, chest tube placement, or when they are treated by radiotherapy. Improper

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

or severe burns of breast tissue may also result in amastia.

Genetics

Congenital amastia can be associated with both autosomal dominant and recessive inheritance. However, in clinical research, autosomal recessive heritage amastia is uncommon. Mutation of genes may disrupt the normal process and results in abnormity of breast. The protein tyrosine receptor type F gene (

PTPRF Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the ''PTPRF'' gene. The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that ...

) is particularly important in nipple-areola region development. PTPRF encodes protein phosphatase which can localize at adherent junction. This phosphatase may also regulate epithelial cell to enable cell- cell interaction. PTPRF is also responsible for growth factor signalling and

Wnt pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...

. Homozygous frameshift mutation in PTPRF may cause amastia, which suggests the causative relationship between PTPRF defect and syndromic amastia.

Management

Since bilateral and unilateral amastia may be attributed to different pathologies, appropriate managements should be adopted accordingly. Bilateral amastia can occur in isolation or associated with other disorders. This case is less understood and difficult to treat. On the other hand, Poland's syndrome is the most common cause of unilateral amastia. Managements such as muscle/breast reconstruction and nipple areola relocation should be provided to these patients.

Breast reconstruction

Surgical treatment for breast defects such as

mastectomy Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...

is also applicable to treat patients with amastia.

Tissue expansion Tissue may refer to: Biology * Tissue (biology), an ensemble of similar (or dissimilar in structure but same in origin) cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth ("tissue moth") found in ...

is the most common technique and can be done by using either autologous or prosthetic tissue. For

autologous Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogene ...

reconstruction, different tissues may be chosen according to patients’ physical condition or their preferences.

Prosthetic In medicine, a prosthesis (plural: prostheses; from grc, πρόσθεσις, prósthesis, addition, application, attachment), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through trau ...

reconstruction may follow the same principles. Flap reconstruction is another method to rebuild the breast surgically. There are various kinds of flaps to choose depending on different situation.

Nipple areola relocation

Amastia is often associated with Poland's syndrome, which requires appropriate reconstructive procedure to stabilize chest wall, transfer dynamic muscle and reposition nipple areola region. The treatment of nipple areola relocation provides space for secondary breast enlargement. In this treatment, the tissue expander can be inserted either beforehand or delayed. It can be placed in different parts of body depending on how many overlying soft tissues the patient has. In order to guide the dissection and make sure the correct location of these tissues, marking of the

inframammary crease In human anatomy, the inframammary fold (IMF), inframammary crease or inframammary line is the natural lower boundary of the breast, the place where the breast and the chest meet. The choice of the term depends on the prominence of the feature. It ...

is required before operation.

References

External links

{{Congenital malformations and deformations of breast Congenital disorders of breasts