Reproduction Function in Male Patients With Bardet Biedl Syndrome

Abstract

Purpose Bardet-Biedl syndrome (BBS) is a ciliopathy with a wide spectrum of symptoms due to primary cilia dysfunction including genitourinary developmental anomalies as well as impaired reproduction particularly in males. Primary cilia are known to be required at the following steps of reproduction function: (1) genitourinary organogenesis, (2) in the fetal firing of hypothalamo-pituitary axe, (3) sperm flagellum structure and (4) the first zygotic mitosis conducted by proximal sperm centriole. BBS phenotype is not fully understood. Methods This study explored all steps of reproduction in 11 French male patients with identified BBS mutations. Results BBS patients presented frequently genitourinary malformations as cryptorchidism (5/11), short scrotum (5/8), micropenis (5/8) but unexpectedly, normal testis size (7/8). Ultrasonography highlighted epididymal cysts or agenesis of one seminal vesicle in some cases. Sexual hormones levels were normal in all patients except one. Sperm numeration was normal in 8 out of the 10 obtained samples. Five to 45% of sperm presented a progressive motility. Electronic microscopy did not reveal any homogeneous abnormality. Moreover, a psychological approach pointed a decreased self-confidence linked to blindness and obesity explaining why so few BBS patients express a child wish. Conclusions PC dysfunction in BBS impacts embryology of the male genital tract, especially epididymis, penis and scrotum through an insufficient fetal androgen production. However, in adults, sperm structure does not seem to be impacted. These results should be confirmed in a greater BBS patient cohort, focusing on fertility.

The Interaction of Obesity and Reproductive Function in Adolescents

“…109 The central hypogonadotropic hypogonadism appears to reverse in adolescence due to increased kisspeptin signaling which contributes to spontaneous puberty in some. 109 Pubertal delay is still common, and infertility is seen in both sexes. 108…”

“…Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive monogenic obesity syndrome with an average worldwide prevalence among Caucasian populations of 1/150,000. 108,109 Higher prevalence can be found among certain populations where consanguinity exists (e.g., Kuwait, Newfoundland). 108 The most common mutations occur in BBS1 and BBS19 genes.…”

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism

“…In addition to being clinically heterogeneous, BBS is genetically diverse with 19 identified loci and complex genetics (i.e., digenicity and oligogenicity) 28 akin to CHH and Kallmann syndrome 16 . Although traditionally associated with CH, a recent clinical study found no evidence for hypogonadism among males with BBS when this was screened for systematically 29 . Prader–Willi syndrome (PWS) is a rare genetic disorder (1/10,000–25,000) on chromosome 15 that causes physical, mental and social disability.…”

Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease

“…Hypogonadism is found in BBS [40], and it is thought to be secondary to impaired organogenesis and sperm function but possibly also a defective hypothalamic-pituitary axis [41].…”