Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.

Rump, Patrick; Hamel, B.C.J.; Pinckers, A.; Dop, P.A. van

doi:10.1136/jmg.34.9.767

Cited by 35 publications

(12 citation statements)

References 18 publications

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“…[4][5][6][7][8][9][10][11][12] There are several distinguishing features between our reported patients and previous reports of Boucher-Neuhauser syndrome. First, the ataxia is spinocerebellar in the Boucher-Neuhauser syndrome, though the spinal component was not always mentioned, 10 whereas in our patients the ataxia was purely cerebellar. Secondly, the onset of ataxia is later in Boucher-Neuhauser syndrome, although in a few patients the onset was early in the second decade (before 15 years).…”

Section: Discussionsupporting

confidence: 54%

“…Thirdly, in Boucher-Neuhauser syndrome the choroid is always involved, but the eye findings are quite variable. 10 In our patients, the choroid was clearly not involved. Lastly, our patients had hypersegmentation of the neutrophilic nuclei, a feature not mentioned in Boucher-Neuhauser syndrome.…”

Section: Discussionmentioning

confidence: 46%

“…Secondly, the onset of ataxia is later in Boucher-Neuhauser syndrome, although in a few patients the onset was early in the second decade (before 15 years). 10 In our patients the onset of ataxia was in the first decade (6 years). Thirdly, in Boucher-Neuhauser syndrome the choroid is always involved, but the eye findings are quite variable.…”

Section: Discussionmentioning

confidence: 59%

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Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new variant of Boucher-Neuhauser syndrome?

Jbour¹

2003

Journal of Medical Genetics

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A number of syndromes have been described in which hypogonadotrophic hypogonadism is associated with multiple somatic and neurological anomalies such as tall stature, anosmia, ataxia, mental retardation, and choroidal dystrophy. [1][2][3][4][5][6][7] The large number of syndromes indicates the considerable clinical heterogeneity associated with hypogonadotrophic hypogonadism. In this report, we describe an unusual constellation of neuroendocrinological findings in an Arab family with three affected sibs. A major finding is hypogonadotrophic hypogonadism associated with short stature owing to gonadotrophic and somatotrophic cellular dysfunction in the anterior pituitary. Although, we discuss several possible modes of inheritance, we speculate that the mode of inheritance of this disorder in this family is autosomal recessive. PATIENTS, MATERIALS, AND METHODSThe family was ascertained through the proband VI.5 (fig 1). All three seemingly affected family members had a detailed evaluation by an endocrinologist, a neurologist, a clinical geneticist, and an ophthalmologist. Three of the four older sibs were examined by the same team and were reported to be normal. The three affected subjects also had electrocardiograms, echocardiograms, brain and pituitary MRI, electromyography, nerve conduction studies, electroretinograms, and electro-oculograms.Patient 1 (VI.5) This male patient is currently 21 years old. He was the product of a 35 week gestation born by normal spontaneous vaginal delivery. At birth, he developed respiratory distress requiring neonatal intensive care for about 6 weeks. He achieved the early milestones of development on time but there is no available record for his growth pattern during the early years.The onset of symptoms was gradual with a slowly progressive ataxic gait around the age of 6 years, which was associated with a progressive decline in his scholastic performance. He presented to us at the age of 20 years, and his height was 1.45 m (<5th centile), weight was 39 kg (<5th centile), and head circumference was 50.5 cm (>2 SD below the mean). He had mild non-progressive bilateral ptosis, and the genital examination showed an infantile penis, small testes, and sparse pubic hair. He had no dysmorphic features or obvious anomalies in the skeletal or cardiovascular systems. He showed evidence of mild impairment of cognitive function (Weschler intelligence scale: verbal IQ 69, performance IQ 47, and full IQ 54). Scanning, dysarthric speech, and multidirectional jerky nystagmus were present. While the saccadic eye movement was abnormal with bilateral hypometric saccades, pursuit eye movement was normal and he had no visual complaints.The neurological evaluation showed normal muscle bulk, without wasting or fasciculations, normal strength throughout, and generalised hypotonia. The deep tendon reflexes were +2 and symmetrical, with a flexor plantar reflex. There were no sensory abnormalities on deep or superficial evaluation. Dysmetria, past pointing, dysdiodochokinesia, and intentional tremors were ...

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 46%

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Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new variant of Boucher-Neuhauser syndrome?

Jbour¹

2003

Journal of Medical Genetics

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“…The early reports have shown diffuse cerebellar atrophy, with one report showing maximum involvement of vermis,8 and others have reported associated mild cortical atrophy 9. Santos et al in 20035 were the first to report additional MRI changes associated with the BNS, which were predominantly T2W white-matter hyperintensities in the periventricular region in cerebral cortices and in basal ganglial structures.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

“…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. The usual MR imaging shows a diffuse cerebellar atrophy and mild cortical atrophy 9.…”

Section: Introductionmentioning

confidence: 99%

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

Kate

Kesavadas

Nair

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

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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.

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Complex movement disorders in a sporadic Boucher‐Neuhäuser Syndrome: Phenotypic manifestations beyond the triad

2009

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Plasma Phenylalanine Level in Dopa-Responsive DystoniaDYT5 is a condition characterized by levodopa (L-dopa) responsive dystonia (DRD) that shows childhood onset and marked diurnal fluctuation. Patients with DYT5 have heterozygous mutations in the GCH1 gene, which codes for GTP cyclohydrolase I (GTPCH), a rate-limiting enzyme in tetrahydrobiopterin (BH 4 ) synthesis. 1 BH 4 is a cofactor for aromatic amino acid hydroxylases including tyrosine hydroxylase (TH), phenylalanine hydroxylase (PAH), and tryptophan hydroxylase. 2 In patients with DYT5, production of dopamine is suppressed due to the decrease of BH 4 because TH is a rate-limiting enzyme in dopamine synthesis. The lack of BH 4 may also affect the activity of PAH, and patients with complete GTPCH deficiency show hyperphenylalaninemia. However, hyperphenylalaninemia has not been reported in patients with DYT5. 3 Therefore, we examined blood phenylalanine levels in patients with DYT5 compared with controls to determine whether the decrease of BH 4 in DYT5 affects PAH activity.Blood samples for analysis of amino acids were obtained from seven patients with DRD 4 and heterozygous mutations of GCH1, 24 patients with dopa nonresponsive dystonia (non-DRD), and 12 controls. The samples were collected in a tube containing EDTA, and plasma was obtained for analysis of phenylalanine and tyrosine levels using an auto-amino acid analyzer (HS-3000; Hitachi, Tokyo, Japan). All data are expressed as means 6 SD. The data were analyzed by analysis of variance (ANOVA) with multiple comparison using the Bonferroni method. A significant difference was defined as a P value < 0.05.The phenylalanine and tyrosine levels in the plasma of patients with DYT5, patients with non-DRD, and controls are shown in Figure 1. The phenylalanine levels in the DYT5 (81.1 6 26.6 lmol/L), non-DRD (60.5 6 14.5 lmol/L), and control (58.7 6 9.1 lmol/L) groups were all within the normal range. However, the phenylalanine level in patients with DYT5 was significantly higher than those in the other groups (P 5 0.027 by ANOVA). Multiple comparison also indicated that the level of plasma phenylalanine in patients with DYT5 was significantly higher than those in patients with non-DRD (P 5 0.043) and in controls (P 5 0.040). There was no significant difference in the plasma phenylalanine levels between patients with non-DRD and controls. There were no significant differences in plasma tyrosine levels among all the groups. BH 4 deficiency causes hyperphenylalaninemia and a decrease of dopamine production, because it suppresses the activity of PAH and TH. Patients with a homozygous mutation in the GCH1 gene are reported to show hyperphenylalaninemia, in addition to DRD. Patients with DYT5 having only a heterozygous mutation in GCH1 also show symptoms of DRD, but do not have hyperphenylalaninemia. Our results indicated that blood phenylalanine levels in patients with DYT5 are within the normal range, but are higher than those in controls, which suggests that the activity of PAH is partially affected by the decre...

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Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome.

Abstract: Genet 1997;34:767-771)

Cited by 35 publications

References 18 publications

Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new variant of Boucher-Neuhauser syndrome?

Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new variant of Boucher-Neuhauser syndrome?

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

Complex movement disorders in a sporadic Boucher‐Neuhäuser Syndrome: Phenotypic manifestations beyond the triad

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