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

Abstract

Boucher-Neuhäuser syndrome (BNS) is rare autosomal recessive disease, characterised by cerebellar ataxia, hypogonadotropic hypogonadism and chorio-retinal degeneration. The authors report a family (brother, 22 years and sister 24 years) with late-onset BNS (>10 years). They had subnormal intelligence; the cerebellar ataxia was progressive over 2 years with early functional dependence. Puberty was attained in a brother with testosterone injections, while the girl had primary amenorrhoea. There were no associated visual complaints. They both had diffuse periventricular white-matter hyperintensities in cerebral cortex and diffuse cerebellar atrophy in the MRI.

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

“…On the level of single families, a possible autosomal-recessive trait of inheritance (several affected siblings, no genetic testing [2,7,18], has been proposed in the past -often in association with parental consanguinity (e.g. [7,18]).…”

“…[7,18]). With recent advances in genetic testing in BNS, resulting in the identification of PNPLA6 as the major target gene and an autosomal recessive pattern, this originally clinically defined entity is becoming part of a larger spectrum of neurodegenerative disorders including Gordon Holmes syndrome, hereditary spastic paraparesis, and spastic ataxia [5].…”

“…Moderate cognitive impairment (see e.g. cases from [7,18]) and peripheral polyneuropathy may be present in substantial fractions as well. Pes cavus [2,4,19] was described by several authors and movement disorders such as focal (craniocervical) dystonia and chorea may develop in BNS [20].…”

Compound heterozygous PNPLA6 mutations cause Boucher–Neuhäuser syndrome with late-onset ataxia

“…Published B–N case descriptions suggest that additional features may be present, including subcortical T2 white matter hyperintensities [7, 22], basal ganglia [3], midbrain [3], and cortical atrophy [23, 24], pyramidal tract abnormalities and hyperkinetic movements (Table 1). Cognitive decline was noted in our patient and others [1, 4, 7, 25], and we suspect it may constitute a more prominent feature than previously recognized [1].…”

“…Gait ataxia in Boucher–Neuhäuser has been typically reported between the first and third decades of life; later ages of onset are rare [1, 3–5]. Although sporadic cases without apparent consanguinity have been reported, most reports are among siblings (about 80 %) [6, 7], often of consanguineous parents [3, 6]. It is unclear whether there is a reporting bias away from sporadic cases in this autosomal recessive disorder, but this seems plausible.…”