User:Lcheng9000/Supernumerary nipples–uropathies–Becker's nevus syndrome

Supernumerary nipples–uropathies–Becker's nevus syndrome (also known as "SNUB syndrome" ) is a skin condition that may be associated with genitourinary tract abnormalities. Supernumerary nipples, also referred to as polythelia or accessory nipples, is a pigmented lesion of the skin that is present at birth. This pigmentation usually occurs along the milk lines, which are the precursors to breast and nipple development. Clinically, this congenital condition is generally considered benign, but some studies have suggested there may be an association with kidney diseases and cancers of the urogenital system. Becker's nevus typically presents as a unilateral, non-cancerous patch of skin that is hyperpigmented and has excessive hair, often occurring on the chest, shoulder. and back. The term "Becker's nevus syndrome" is used to describe Becker's nevus occurring along with other skin, musculoskeletal, or other tissue abnormalities such as supernumerary nipples. There are some reports documenting an association between supernumerary nipples, Becker's nevus syndrome, and urinary tract abnormalities, although with conflicting results. This association has been dubbed "SNUB syndrome".

SNUB syndrome may be considered part of the broader category of epidermal nevus syndromes, which is described as the presence of any type of epidermal nevus together with other developmental abnormalities in the skin, eyes, brain, heart, skeletal system, or urinary or genital systems. Genitourinary tumors, such as kidney or bladder cancers, have been reported to occur earlier in life and more often in individuals with epidermal nevus syndrome. However, there have not been sufficient controlled clinical studies to confirm the association between epidermal nevi and kidney and urinary tract abnormalities. On the other hand, studies on supernumerary nipples have found an association between supernumerary nipples between kidney and urinary tract abnormalities. While the prevalence of urinary tract abnormalities is about 1-2% in the general population, the frequency can rise to about 14.5% in individuals with supernumerary nipples.

Clinical Studies and Case Reports
The association between supernumerary nipples (also known as polythelia or accessory nipples) and urinary tract abnormalities has not been fully established yet in both adults and children. In some clinical studies, the presence of supernumerary nipples is an indication of the presence of nephrouropathies in children, and in others, an association between the two has not been proven to be statistically significant. Studies have yet to show the association (or no association) in adults, but the majority have been linked to children.

The correlation between the accessory nipples and renal abnormalities was first introduced by K. Mehes in 1979 in a study of 20 children with polythelia. In this study, eight out of the twenty children had kidney lesions, proving statistically significant data and concluded an association between supernumerary nipples and renal abnormalities.

However, a 1992 study by M. Armoni found evidence to support that accessory nipple were not associated with urinary tract malformations. This study screened 102 infants and children with accessory nipples for urinary tract malformations using ultrasound. No urinary tract malformations were found in the children, which led to their conclusion that routine ultrasounds were not necessary in their institution (Barzilai Medical Center, Israel).

In 1996, a study published by C. Urbani, M.D. and R. Betti, M.D. evaluated accessory mammary tissue (AMT) association with hereditary urinary and kidney abnormalities. In their study, they aimed to determine the significance of the association in the adult population since control studies were only based on newborns and children. They enrolled 146 white patients (men and women) with AMT with a total of 2645 patients. 11 patients with AMT were found to have kidney and urinary tract abnormalities. The study concluded that multiple factors are of importance in the determination of an association. These factors include age, race, ethnic group, hypertension, alcoholism and recently embryonic development defects. They found that there was a significantly higher occurrence of kidney and urinary abnormalities in patients with AMT compared to the control group, but no association or correlation was concluded between them.

In addition to clinical study findings, many case reports are also published providing a resource for the presence (or no presence) of kidney and renal abnormalities in patients with polythelia and familial polythelia. In one case report by A. Leung, renal abnormalities were recorded in a Chinese family father with polythelia and no findings of kidney/urinary tract abnormalities in his twin daughter's renal ultrasound. Whereas in other case reports by Hersh et al, recorded significant renal abnormalities in a family with polythelia. Both mother and daughter had significant renal cysts. These case reports provide controversial data regarding the association between polythelia and kidney/urinary tract abnormalities.

While these clinical studies and case reports provide controversial conclusions, the presence of polythelia in patients warrants physicians to be vigilant in their examinations and perform the necessary tests for kidney/urinary tract abnormality detections early in the course of their diagnosis.

Signs and Symptoms
Individuals with SNUB syndrome will have the characteristic symptoms of Becker's Nevus, supernumerary nipples, and some type of uropathy.

Becker's nevus presents as a tan or brown patch of skin that most often occurs on chest, shoulder blade, or back, although it can occur on other parts of the body. This patch of skin can develop excess growth of coarse, dark hair years after the discoloration is first discovered. The term Becker's nevus syndrome is used when an individual has a Becker's Nevus along with other developmental abnormalities. The most common abnormality is ipsilateral breast hypoplasia, where the breasts are asymmetrical in size, shape, or placement. Other abnormalities can include scoliosis, fused ribs, and asymmetry in other muscles. When Becker's nevus syndrome presents specifically with supernumerary nipples and urogenital abnormalities, it may be referred to as SNUB syndrome.

The urogenital abnormalities seen with SNUB syndrome are more difficult to characterize, since very few studies have investigated individuals with all three symptoms (Becker's nevus, supernumerary nipples, uropathy). One study found multiple cases of children with Becker's nevus and supernumerary nipples, with one of those children also having polycystic kidney disease. Another child had Becker's nevus but no supernumerary nipples, but had Wilm's tumor (kidney cancer). Some studies on supernumerary nipples have found associations with a myriad of kidney and urinary tract abnormalities, including polycystic kidney diseases, renal cysts, and narrowing of the ureter tube. Patients with cancer of the urinary or genital systems have also been reported to have higher rates of supernumerary nipples. There is a wide range of kidney and urinary tract abnormalities reported to be associated with Becker's nevus or supernumerary nipples. However, whether there is a true association between uropathies, Becker's nevus, and supernumerary nipples is debated in the literature.

Causes
Supernumerary nipples is a rare congenital disease that may happen in both females and males. During human embryologic development, the ectodermal clusters along the milk lines to form breasts. In normal development, two ectodermal clusters will form breasts; the rest of the ectodermal clusters will regress. If the rest of the ectodermal clusters continue growing, they will form accessory nipples. Various studies found an association between supernumerary nipples and uropathies, but no causation was established between these two conditions. The cause of Becker's nevus is not well known yet. It is considered a congenital condition, but the appearance of the nevus seems to depend on an individual's androgen levels. The Becker's nevus will often become more obvious during puberty, especially in male individuals. Other studies suggest it may relate to a genetic mutation of beta-actin. Although some studies describe the association between supernumerary nipples, Becker's nevus, and urinary tract abnormalities as "SNUB syndrome", there is no clear causal relationship between the three conditions.

Diagnosis
Because of the rarity of SNUB syndrome, diagnostic methods for this particular syndrome have not been thoroughly described in the literature. Therefore, this section will describe diagnostic methods used for supernumerary nipples and epidermal nevus syndromes, including Becker's nevus syndrome in particular.

Skin biopsy
Becker's nevus and supernumerary nipples can usually be diagnosed by visually observing the skin. However, if visual observation alone is insufficient to make a conclusive diagnosis, a skin biopsy can be performed. A small sample of skin can be removed from the nevus and examined under a microscope to analyze the cellular components. Epidermal nevi will typically contain an abnormal overgrowth of keratin-producing cells, sweat glands, and hair follicles. There is also typically increased levels of melanin in the innermost layer of the skin, causing the darker discoloration.

Urinary system evaluation
Ultrasound, CT scans, and other imaging technology can be used to evaluate for kidney or bladder cancers. Urinalysis can also be performed on urine samples to evaluate for other urinary tract problems, such as hematuria.

Epidemiology
The epidemiology of SNUB syndrome has not been thoroughly described in the literature. The sex ratio of Becker's nevus. Becker's nevus occurs more commonly in males than females;

History
Becker's Nevus syndrome with uropathies