I am a Recklinologist at several levels.
- I have been involved with NF1 patient care since 1969.
- I am a clinical researcher; in 1977 I founded the world’s first NF-dedicated research organization, the Baylor NF Program (BNFP), in Houston, TX.
- I am a basic researcher, with decades of experience doing laboratory-based research on tissue and cells derived from NF1 lesions.
- I am an evolutionist, appreciating NF1 as a disorder and the NF1 gene as a means to understand the interaction of humanity and evolution in general. Recognizing the NF1 locus on human chromosome 17 as a “supergene”1-4 is an important element of progress in this regard. Another step forward is characterizing elements of human anatomy that are poorly understood or even ignored.
As I began exploring the need for considering sexual behavior in NF1, I also realized that this was an opportunity to consider broader issues intrinsic to concerns about NF1, such as epigenetics, supergenes and homology.
This Update is not about fertility. Fertility appears not to be compromised in NF1. On the other hand, genetic fitness is an issue, but I will only make brief mention of it here. Genetic fitness, the likelihood of having offspring, is decreased in populations of men with NF1, as documented substantially by Crowe, Schull and Neel in 1956.5 The mechanism appears to be that NF1 men have fewer marriages and opportunities for procreation. In this context, one might ask, “Why should a person with NF1 have problems with sexual performance and sexual satisfaction?”
Let us start with neurofibromas. As part of NF1, neurofibromas can occur anywhere on the body. Among the most challenging locations, from a clinical perspective, is the lower portion of the trunk where it is joined by the thighs. Particularly important there are the external and internal genitalia. Any and all of those body parts can manifest neurofibromas of all four types: cutaneous (CN), subcutaneous (SN), diffuse plexiform (DPN) and nodular plexiform (NPN).6 Neurofibromas of either type located in the perineurium and/or pelvis may compromise both the genitalia per se and, obviously, sexual behaviors.
In addition, virtually every adult woman with NF1 has a special type of CN that involves the nipples and surrounding darkly pigmented skin, the areola.7-10 These nipple/areolar neurofibromas may be few in number and/or small, but also numerous and quite large. In any event, they represent an unequivocal cosmetic compromise of special importance. Beyond the problems they may pose for the suckling infant, they detract from the usual, ordinary elements of female sexual appeal and gratification.
There are many ways neurofibromas can interfere with sexuality and sexual performance. And, yet, this subject is rarely, if ever, discussed with an NF1 person – in just about any circumstance. There are very few publications by Recklinologists or sexual behavior specialists that address sexuality – and especially female sexual satisfaction – as it relates specifically to the NF1 syndrome. It is virtually never a topic of discussion at NF1 professional and advocacy meetings. In my 40-plus years of NF1 involvement, I have seen such subjects broached at only one NF event: in Cardiff, Wales, October 2013. As part of a presentation, “Living with NF1,” a woman with NF1 shared her concerns. During these same four decades, on hundreds and hundreds of occasions when I have engaged women with NF1, I have never been queried by an NF1 patient (or spouse or parent) about the consequences of NF1 for sexual performance and behavior – even when pelvic and/or vulvar neurofibromas were present. Ultimately, I also have to acknowledge that I myself did not make such inquiries easy.
Starting from these acknowledgements, I have begun to make a special effort to understand the issues and facts involved – and make a special effort to facilitate meaningful discussions, both in private clinical settings and in appropriate public venues.
The UrethroVaginal Gland (UVG) has been known since antiquity as the source of fluid that flows through the female urethra in association with the initiation of sexual activity.11-13 The ancient Sanskrit word for the fluid is amrita.14 Amrita’s primary purpose is lubrication of the vagina preparatory to sexual intercourse. 11 Another purpose may be an antimicrobial function.15 The amrita is ejected into the introitus through the urethra and/or through small ducts parallel to and adjacent to the tip of the urethra. (The ducts themselves were described in detail by Alexander J.C. Skene in 1880 and are thus sometimes referred to as “Skene ducts.”16) In addition, a particularly intense, forceful secretion of amrita can sometimes occur as part of female orgasm and even be associated with a uniquely intense orgasm. (Unfortunately, this aspect of the UVG and amrita has been lasciviously exploited by purveyors of “blue movies” [pornography], tending to give this whole subject an undeserved and mistaken sordidness.)
For our present purposes, we must scientifically and clinically acknowledge that the UVG and amrita exist and are thereby relevant to any thorough considerations of female sexual health.11 Through the present, they (UVG and amrita) have not been considered as carefully as they should for human females in general and NF1 specifically.
For example, they have been totally overlooked or ignored in investigating the disorder, Meyer-Rokitansky-Kuster-Hauser (MRKH) syndrome, a birth defect involving the urogenital sinus, the anatomic site of origin of the UVG and the prostate gland.17, 18
Human NF1, Mouse Nf1 and the Shared Urethrovaginal Gland. Shortly after the initial mouse models for the NF1 syndrome indicated that the mice, in general, did not manifest CN, I was very curious about this discrepancy. In order to investigate anatomic bases, I microscopically studied a series of full-thickness skin samples from some of Professor Yuan Zhu’s Nf1+/- mice.19 Thereupon, I was reminded of the cutaneous trunci musculature (CTM), a band of striated muscle dividing the skin (cutaneous and subcutaneous) per se from deeper tissues of the trunk.20 Evolutionarily, this muscle complex was originally part of the upper limb, innervated by cervical nerve 8 and thoracic nerve 1. At some point in evolution, this specific muscle tissue became part of the trunk (axial musculature) and assumed several unique functions. In the cat, it is known as the cutaneous maximus, and is thereby familiar to anyone who has stroked a cat’s back: the back arches acutely and the tail is lifted straight up. This latter tail movement is prototypic for the CTM, displacing the tail from the perineum, in particular the anal orifice and the introitus. This displacement is especially important both to facilitate sexual intercourse and passage of the newborn from the vagina into the outside world. The key portion of the central nervous system (CNS) that controls the CTM and many of the pelvic muscles involved in both sexual intercourse and delivery is the Nucleus ambiguus. It also turns out that the N. ambiguus also controls the UVG. The key point here is that an inquiry about cutaneous neurofibromas in the mouse model led to identification of key element of mammalian sexual behavior. Moreover, this “discovery” took place at just about the time I was becoming determined to consider NF1 sexuality more intensely.
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