A New Family of Boucher-Neuhauuser Syndrome: Coexistence of Holmes Type Cerebellar Atrophy, Hypogonadotropic Hypogonadism and Retinochoroidar Degeneration: Case Reports and Review of Literature.

Abstract

Abstract. The association of familial hypogonadism with progressive cerebellar ataxia is only rarely encountered, and the exact link between the symptoms remains unknown. We report here two sisters presenting with Holmes type cerebellar ataxia, hypogonadotropic hypogonadism and retinochoroidal degeneration recently diagnosed as Boucher-Neuhauser syndrome. There was consanguinity between the parents of the affected individuals and the condition seemed to be inherited as an autosomal recessive defect. On endocrinological examinations, in both cases, the responses of LH and FSH to LH-RH (100 jug) were impaired even after repetitive stimulation with LH-RH (400 jig, 7 days), suggesting that the hypogonadism was due to a primary pituitary disturbance. Impaired GH responses to GRF (100 ug) and insulin-induced hypoglycemia (0.1 U/kg) were also noted. The two sisters shared an almost identical clinical and endocrinological picture. Their karyotypes were 46, XX. They had been treated for primary and secondary amenorrhea at the age of 20 years and neurological problems had started at the age of 30 years. This unique family displays clinical evidence of a possible common mechanism responsible for a progressive hypothalamo-pituitary and cerebellar impairment of late onset.

Late-onset Boucher-Neuhauser Syndrome (late BNS) associated with white-matter changes: a report of two cases and review of literature

“…Delayed puberty or secondary amenorrhoea was seen as presenting manifestation in remaining 20% of patients (6/30). Endocrine abnormality noted is hypogonadotrophic hypogonadism due to pituitary or hypothalamic functional defect 4 7. These patients are treated by replacement therapy and respond adequately.…”

“…It was first described in 1969 by Boucher et al in two siblings 1. The BNS patients described in the literature have heterogenous phenotypic presentations in addition to the classical triad with hypersegmented neutrophils,2 3 hypocalciuric hypercalcaemia,4 central demyelinating changes5 6 pyramidal tract involvement6 7 etc. They have a variable age of symptom onset1 3 (4–40 years) and variable symptom at onset, the commonest being the cerebellar type of ataxia which is usually slowly progressive with minimal disability 4.…”

“…The BNS patients described in the literature have heterogenous phenotypic presentations in addition to the classical triad with hypersegmented neutrophils,2 3 hypocalciuric hypercalcaemia,4 central demyelinating changes5 6 pyramidal tract involvement6 7 etc. They have a variable age of symptom onset1 3 (4–40 years) and variable symptom at onset, the commonest being the cerebellar type of ataxia which is usually slowly progressive with minimal disability 4. The hypogonadism is responsive to supplementation8 with testosterone in males and an estrogen/progesterone combination in females with successful completion of pregnancy.…”

Boucher–Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature

“…Eleven out of 42 patients had a short stature. Laboratory abnormalities included hypersegmented neutrophils (n=7) and hypercalciuric hypocalcaemia (in two siblings [11]). Results from lumbar puncture were available in two cases only (being reportedly normal).…”

Prominent Expression of Spinocerebellar Ataxia Type-1 (SCA1) Gene Encoding Ataxin-1 in LH-Producing Cells, L.BETA.T2

“…Taking these findings together, SCA1 is likely to be involved in regulation of gene expression and in pre-mRNA processing in Purkinje cells. In addition, there are several case reports on the Boucher-Neuhauser syndrome [25,26], demonstrating a pituitary gonadotropin deficiency in cerebellar ataxia patients. These observations suggest a relationship between the mutation of SCA1 gene and hypogonadism.…”