LMBBS is a rare familial disorder, inherited by autosomal recessive characteristic with variable penetrance and expressivity [1]. It is a result of consangious marriages mostly [2]. The incidence varies markedly between 1:140,000 to 1:160,000 live births in North America and Europe and 1:65,000 in an Arab population [3]. Its incidence is highest in Middle Eastern countries due to higher number of consangious marriage practice in these countries [2]. The primary features of this syndrome include retinal dystrophy, polydactyly, obesity, hypogonadism, renal abnormalities and mental retardation. However, LMBBS may also present with other secondary abnormalities, including speech disorder and developmental delay, ataxia, diabetes insipidus and dental crowding [4]. The patients of LMBBS have a smaller size pituitary gland due to which a number of hormonal irregularities are present. There is decreased production of sex hormones, estrogen and progesterone. Due to this there are undescended testis, micro penis, absent secondary sexual characters and gynaecomastia in males [4]. According to Thorup et al. [5] cryptorchidism is an accepted risk factor for testicular cancer with relative risk 3.7-7.5 times higher than normal population. Here we are reporting a case of LMBBS in a 45 years old male with bilateral undescended testis diagnosed with seminoma testis.

A 45 years old male patient, who was a known case of LMBBS presented to our hospital with history of pain abdomen for three weeks. He was a full term delivery at home, youngest of five siblings. Marriage of parents was non consangious. There was axial polydactyly, extra digit on both right and left hands and on both feet. His milestones were normal till age of 7 years. There was history of obesity from age of two years to date. There was history of night blindness which has progressed over years and now there was complete blindness. There was no genital ambiguity at birth. Presently, he had a micro penis, empty scrotal sacs and gynaecomastia. After age of 7 years, there was scholastic delay and learning problems. His IQ was 70 and suggested mental retardation. Dental crowding was present. He was a typical case of LMBBS as the pentad of features of polydactyl, obesity, blindness, learning disability, hypogonadism was present. He did not receive any treatment for LMBBS due to financial constraints. He started having complaint of pain abdomen which a mild to moderate pain, generalized to whole abdomen, non-radiating and non-progressive. Further work up was done and blood investigations were suggestive of normal blood counts and biochemistry profile. An ultrasound of abdomen was done suggestive of hepato-spleenomegaly, empty scrotal sac with large solid abdomino-pelvic mass with gross ascites likely bilateral testicular neoplasm. A contrast enhanced CT scan of abdomen and pelvis was done suggestive of large testicular germ cell tumor in retroperitoneum, right paracolic gutters arising from bilateral undescended testis. There was gross ascites. A biopsy was done of the mass which was suggestive of seminoma testis. Marker study was done suggestive of AFP was in normal range 3.30ng/mL, LDH was raised more than 1200U/L and HCG was raised 164.0mIU/mL. Patient attendants were counseled regarding nature of disease, prognosis and treatment with chemotherapy. They denied any further work up and opted for palliative care only.

LMBBS is a rare familial disorder, inherited by autosomal recessive characteristic with variable penetrance and expressivity [1]. It is a congenital ciliopathy manifesting with primary and secondary characteristics affecting function of brain, eyes, kidneys, hand and feet. The incidence varies markedly between 1:140,000 to 1:160,000 live births in North America and Europe and 1:65,000 in Arab population [3]. Its incidence is highest in Middle Eastern countries due to higher number of consangious marriage practice in these countries [2].

Literature suggests that Laurence-Moon and Bardet-Biedl syndrome are two different entities with overlapping features. Studies suggest that obesity and polydactyly are features of BBS, while spasticity is present in LMS. On the other hand there are genotypic and phenotypic correlations between them making them to be considered as a single entity [3].

The primary features are polydactyly, retinitis pigmentosa, obesity, learning disability and hypogonadism while secondary features include ataxia, poor coordination, speech abnormalities, brachydactyly, diabetes mellitus, hearing loss, hepatic fibrosis, cardiovascular anomaly and spasticity [6]. Forsythe and Beales gave a criterion for diagnosis of LMBBS as either four major characteristics or three major, together with two minor traits, is sufficient. Our patient was a typical case of LMBBS, as features of polydactyl, obesity, blindness, learning disability, hypogonadism were present [7]. 

Kelvin et al. suggested that LMBBS is characterized by 5 cardinal features-obesity (95%), mental retardation (90%), retinal degeneration (90%), hypogonadism (75%) and polydactyly (75%). The pentad of symptoms is present in less than half of the cases [8].

The patients of LMBBS have a smaller size pituitary gland due to which a number of hormonal irregularities are present. There is decreased production of sex hormones, estrogen and progesterone. Due to this there are undescended testis, micro penis, absent secondary sexual characters and gynaecomastia in males [4].

Cyptorchidism or mal descended testis either unilateral or bilateral are present in about 2-4% of boys globally. Testicular cancer is the most common solid tumor malignancy in men and affects 1% of male population. Average age group is 15-45 years. About 10% of all cases of Testicular Germ Cell Tumors (TGCT) occur in men with history of cryptorchidism. Cryptorchidism is an established risk factor for TGCT. The relative risk is 3.7-7.5 times higher than normal population [5].

During embryonic development testis develop intra abdominally and later descend through the inguinal cord into the scrotum. Two models are suggested for cryptorchidism, first one involves deficiency of INSL3 which is a small peptide hormone that belongs to relaxin/insulin like family expressed in Leydig cells [9]. The second model is deficiency of androgen production, as most processes in descent of testis are androgen dependant and its deficiency causes cryptorchidism [10]. A non functional Hypothalamo-Pitutary-Gonadal (HPG) axis results in hypogonadotrophic hypogonadism. There is decreased production of GNRH, LH, testosterone and INSL3 causing mal descent of testis [11].

In cryptorchid testis, there is insult to both germ cells and somatic cells of testis as the temperature is 37°C within the body cavity compared to the required optimal temperature of 32°C. Haploid germ cells are more susceptible to insult by higher temperature than somatic cells. The elevated temperature of the undescended testis inhibits the differentiation of spermatogonia resulting in an arrest of spermatogenesis, reduced seminiferous tubule size, germ cell depletion and fibrosis. They are pluripotent germ cells which are precursor cells for the development of TGCT. The most common type of TGCT is seminoma [12,13].

In our patient there was bilateral cryptorchidism. Bilateral testes were present in the abdominal cavity. They underwent malignant transformation and presented as large retroperitoneal mass, which after biopsy were suggestive of seminoma testis. 

Our patient was a classical case of LMBBS and was diagnosed with seminoma testis. His attendants were counseled regarding disease and suggested chemotherapy. But they denied treatment and opted for palliation only. 

LMBBS is a rare entity and its association with seminoma testis is even rare. Effective screening strategies for seminoma along with treatment strategies are needed for patients with LMBBS in future.

Our patient was a diagnosed case of LMBBS. He had bilateral mal descended testis and developed seminoma testis. More studies are needed to effectively study this condition and devise effective diagnostic and treatment strategies in future.

1. Bell, J. The Laurence-Moon syndrome. In: The Treasury of Human Inheritance, Penrose L.S. (Eds.). Part III, vol. 5. Cambridge University Press, London, 1958, pp. 51–96.

2. Qadar, L.T. et al.“Laurence-Moon-Bardet-Biedl Syndrome with coexisting abdominal distension and positive fluid thrill: A rare manifestation reported in Karachi, Pakistan.” Cureus, 2019, vol. 11, e4885. https://doi.org/10.7759/cureus.4885

3. Moore, S.J. et al.“Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: A 22‐year prospective, population‐based, cohort study.” American Journal of Medical Genetics, vol. 132, 2005, pp. 352–360.

4. Forsyth, R.L. and M. Gunay-Aygun. Bardet-Biedl syndrome overview. In: GeneReviews. Adam M.P. et al. (Eds.)., University of Washington, Seattle, 2003.

5. Thorup, J. et al. “What is new in cryptorchidism and hypospadias - a critical review on the testicular dysgenesis hypothesis.” Journal of Pediatric Surgery, vol. 45, 2010, pp. 2074–2086. https://doi.org/10.1016/j.jpedsurg.2010.07.030

6. Mahmood, S.H. et al. “A unique manifestation of Bardet-Syndrome with otolaryngologic symptoms and bronchopneumonia in a one-year-old girl.” Cureus, vol. 11, 2019, pp. e5717. https://doi.org/10.7759/cureus.5717

7. Forsythe, E. and P. Beales. “Bardet-Biedl syndrome.” European Journal of Human Genetics, vol. 21, 2013, pp. 8–13. https://doi.org/10.1038/ejhg.2012.115

8. Kelin D. and F. Amman. “The syndrome of Laurence-Moon-Bardet-Biedl and allied diseases in Switzerland.” Journal of Neurological Sciences, vol. 8, 1969, pp. 479–513.

9. Adham, I.M. et al.“The overexpression of the insl3 in female mice causes descent of the ovaries.” Molecular Endocrinology, vol. 16, 2002, pp. 244–252. https://doi.org/10.1210/me.16.2.244

10. Hutson, J.M. et al.“Anatomical and functional aspects of testicular descent and cryptorchidism.” Endocrine Reviews, vol. 18, 1997, pp. 259–280. https://doi.org/10.1210/er.18.2.259

11. Klonisch, T. et al. “Molecular and genetic regulation of testis descent and external genitalia development.” Developmental Biology, vol. 270, 2004, pp. 1–18. https://doi.org/10.1016/j.ydbio.2004.02.018

12. Yin, Y. et al. “P53 and FAS are sequential mechanisms of testicular germ cell apoptosis.” Journal of Andrology, vol. 23, 2002, pp. 64–70.

13. Skakkebaek, N.E. et al. “Carcinoma-in-situ of the testis: Possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma.” International Journal of Andrology, vol. 10, 1987, pp. 19–28. https://doi.org/10.1111/j.1365-2605.1987.tb00161.x