There are multiple abnormalities of the breast that arise from faulty embryologic mechanisms. These may involve and affect the development of the nipple, the mammary glandular tissue, or the entire breast. Multiple classification systems exist that group the types of defect according to the component of the breast that is affected or the location of these components. However, we agree with Elwood [6] that the precise description of the anatomic defect is more helpful and direct.

Congenital inversion of the nipple is a condition in which mesenchymal infiltration and proliferation beneath the mammary pit does not occur, leading to flat or inverted nipples. This may occur unilaterally or bilaterally having significant functional and aesthetic consequences. Its frequency has been estimated as 17.7 per 1000 women [7], although in a Korean series its prevalence was found to be 3.26% [8]. The majority of congenital inverted nipples can be classified as umbilicated [8, 9] and the rest as invaginated. An important clinical point is that congenital inverted nipples must be differentiated from instances of secondary or acquired nipple inversion, which may due to carcinoma, chronic ductal mastitis, macromastia, and post-breast reduction surgery [10]. Several reconstruction techniques have been described to correct inverted nipples. These range from creating tightness at the neck of the inverted nipple, to dividing the lactiferous ducts and adding soft tissue bulk, to duct-preserving operations with release of fibrosis and placement of purse string sutures [9, 10], and more recently, to a contemporary technique based on the principle of tissue expansion involving body jewelry [11].

Athelia is defined as the absence of the nipple-areola complex. It almost invariably occurs in conjunction with absence of glandular tissue, which together result in complete absence of the breast. Amastia or complete absence of the breast is a rare condition defined by the absence of one or both breasts and nipples. This results from failure of the mammary ridge to develop at 6 weeks of gestation. It is important to note that this condition features different patterns of familial inheritance and may be associated with other anomalies. The original classification dates back to 1965 by Trier, who reported on a series of 43 patients with congenital absence of the breast and classified them according to mode of inheritance and association with anomalies [12]. Since then, only six other cases have been reported in the literature [13, 14]. When this defect is unilateral and occurs in association with absence of pectoral muscles, it is known as Poland’s syndrome. Bilateral congenital absence of the breast in association with ectodermal dysplasia is transmitted in a sex-linked recessive pattern, thus only affecting boys. Other patterns of inheritance include autosomal dominant and autosomal recessive [14].

Athelia may occur in the presence of breast tissue (isolated athelia), very rarely at the normal anatomic site but not infrequently at other accessory locations [1]. A review by Ishida, et al. [15] revealed that ectodermal dysplasia, a hereditary disease of the skin and its appendages, underscores the majority of reports of athelia in the literature. In their case report of isolated athelia, the authors make reference to deficient parathyroid hormone-related protein production as a potential causative factor. This molecule was shown to induce mammary mesenchymal cell formation, triggering morphogenesis of the nipple epidermis [16]. Athelia may also be one of the clinical features in Al-Awadi/Raas-Rothschild syndrome, choanal atresia-athelia syndrome and scalp–ear–nipple syndrome [15]. Historically, the labia minora skin graft was proposed for nipple reconstruction [12], however tattooing of the hypochromic skin is a more recently used and less deforming alternative.

Polythelia is a common abnormality of breast development in which extra-thoracic areas of the mammary ridge do not regress, leading to the formation of supernumerary nipples. These remnants can also develop into complete mammary glands, a condition known as polymastia. This occurs most frequently along the milk line in the axilla, followed by the submammary location. They may also be found in the groin area. However, migration of the embryonic rests [17] may account for polythelia or polymastia found in ectopic locations beyond the mammary ridge, such as the perineum [18], the vulva [19], the posterior thigh [20], and the neck [21]. The prevalence of polythelia ranges from 0.22 to 5%, varying considerably among different ethnic groups. In white European children, polythelia was least prevalent at 0.22% [22], in Black neonates, it was noted to be 1.63% [23], and in Jewish neonates 2.5% [24]. The results of a study by Jaber in 1988 [25] demonstrated a higher prevalence of supernumerary nipples in Arab children—4.7% in infants and 5% in children. This finding was attributed to differences in ethnicity, as well as to high rates of consanguinity in many of the participating families. Other interesting findings in this ethnic group included high incidence of left-side location and positioning just below the normally situated nipple, as well as same sex distribution. A large, early case series dated 1879 by Bruce reported a prevalence of 1.54% among a population of 3956 patients in London [26]. He found that supernumerary nipples occurred more than four times as frequently in men as in women. In addition, there was a remarkable preponderance of supernumerary nipples on the left side. As for the location of supernumerary nipples, the majority of the cases were found on the front of the trunk just below the normal breast near the midline. In a study by Schmidt [27], the prevalence of supernumerary nipples was reported as 5.6% in a series of 502 Caucasian infants. In this series, the higher prevalence may be explained by the fact that both supernumerary areola and supernumerary areola with nipple were ascertained in this population. In fact, supernumerary areola without nipple predominated in this series, as well as predilection for left side and male gender.

While the majority of instances of polythelia occur in sporadic fashion, familial polythelia also has been documented in sequential generations and in siblings [28]. Most pedigrees are consistent with autosomal dominant inheritance with variable expressivity, although X-linked dominant and recessive modes of inheritance are also known to occur [29]. The occurrence of left-sided pseudomammae (nipple and areola with no glandular tissue) inferomedial to the normal breast along the mammary line may be suggestive of a “hereditary” trait of familial cases of accessory mammary tissue. This finding was reported to occur in 72% of the patients in Urbani’s familial series [29]. By comparison, there is a higher frequency of polythelia (nipple only) in the sporadic forms of the condition.

The association of polythelia with genitourinary anomalies has been the subject of debate for many years and still remains unclear whether such link exists. A broad spectrum of nephrourinary defects has been described, including adult polycystic kidney disease, renal agenesis, cystic renal dysplasia, familial renal cysts, and congenital stenosis of the pyeloureteral junction [29]. In one of the first studies examining this issue, Mehes demonstrated that 40% of patients with polythelia also had renal abnormalities, mostly obstructive, an 800-fold increase beyond what would be expected by chance alone [30].This association was later corroborated in a larger study of 10770 infants and children [31], as well as by other investigators [32, 33]. Nevertheless, others have found no such correlation and have challenged this view [18, 23, 24]. Based on their extensive review of the literature, Leung and others recommend at the minimum, an awareness of the possible urologic implications of polythelia, leading to a detailed family history, complete physical examination, and a screening abdominal ultrasound in patients with a definitive diagnosis of polythelia [18, 29].

Sporadic and familial polythelia may also be associated with malignancies of the genitourinary tract such as kidney, testes, prostate, and urinary bladder [34]. Cohen has advocated the inclusion of polythelia in the group of conditions known as genodermatoses with malignant potential, which are inherited disorders of mucocutaneous features predisposing to internal neoplasms [35]. This should prompt surveillance for polythelia-related urinary anomalies and malignancies in patients with supernumerary nipples.