Boucher-Neuhauser Syndrome (BNHS)

Categories: Endocrine diseases, Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Boucher-Neuhauser Syndrome

MalaCards integrated aliases for Boucher-Neuhauser Syndrome:

Name: Boucher-Neuhauser Syndrome 57 12 58 73 36 15
Ataxia-Hypogonadism-Choroidal Dystrophy Syndrome 12 20 43 58 29 6
Spinocerebellar Ataxia, Hypogonadotropic Hypogonadism, and Chorioretinal Dystrophy 57 43 73
Chorioretinal Dystrophy, Spinocerebellar Ataxia, and Hypogonadotropic Hypogonadism 43 44 71
Bnhs 57 43 73
Boucher-Neuhäuser Syndrome 20 43
Chorioretinal Dystrophy, Spinocerebellar Ataxia and Hypogonadotropic Hypogonadism 20
Cerebellar Ataxia with Hypogonadism and Choroidal Dystrophy Syndrome 43
Ataxia - Hypogonadism - Choroidal Dystrophy 20
Boucher Neuhauser Syndrome 39
Bns 43


Orphanet epidemiological data:

ataxia-hypogonadism-choroidal dystrophy syndrome
Inheritance: Autosomal recessive; Age of onset: Childhood;


57 (Updated 05-Mar-2021)
autosomal recessive

progressive disorder
some features are variable, even within families
neurologic signs onset during adolescence or young adulthood
ophthalmologic signs onset in first to sixth decade
some patients become wheelchair-bound


boucher-neuhauser syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset progressive


Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases

External Ids:

Disease Ontology 12 DOID:0111265
OMIM® 57 215470
KEGG 36 H02140
SNOMED-CT 67 715984007
ICD10 via Orphanet 33 G11.8
UMLS via Orphanet 72 C1859093
Orphanet 58 ORPHA1180
MedGen 41 C1859093
UMLS 71 C1859093

Summaries for Boucher-Neuhauser Syndrome

MedlinePlus Genetics : 43 Boucher-Neuhäuser syndrome is a rare disorder that affects movement, vision, and sexual development. It is part of a continuous spectrum of neurological conditions, known as PNPLA6-related disorders, that share a genetic cause and have a combination of overlapping features. Boucher-Neuhäuser syndrome is characterized by three specific features: ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy.Ataxia describes difficulty with coordination and balance. In Boucher-Neuhäuser syndrome, it arises from a loss of cells (atrophy) in the part of the brain involved in coordinating movements (the cerebellum). Affected individuals have an unsteady walking style (gait) and frequent falls.Another key feature of Boucher-Neuhäuser syndrome is hypogonadotropic hypogonadism, which is a condition affecting the production of hormones that direct sexual development. Affected individuals have a delay in development of the typical signs of puberty, such as the growth of facial hair and deepening of the voice in males, and the start of monthly periods (menstruation) and breast development in females. Other hormone abnormalities lead to short stature in some affected individuals.The third characteristic feature of Boucher-Neuhäuser syndrome is eye abnormalities, most commonly chorioretinal dystrophy. Chorioretinal dystrophy refers to problems with the light-sensitive tissue that lines the back of the eye (the retina) and a nearby tissue layer called the choroid. These eye abnormalities lead to impaired vision. People with Boucher-Neuhäuser syndrome can also have abnormal eye movements, including involuntary side-to-side movements of the eyes (nystagmus).The key features of Boucher-Neuhäuser syndrome can begin anytime from infancy to adulthood, although at least one feature usually occurs by adolescence. Ataxia is often the initial symptom of the disorder, but vision problems or delayed puberty can be the earliest finding. Vision and movement problems worsen slowly throughout life and can result in blindness or the need for a wheelchair for mobility in the most severely affected individuals.People with Boucher-Neuhäuser syndrome can have additional medical problems, including muscle stiffness (spasticity); impaired speech (dysarthria); and difficulty processing, learning, or remembering information (cognitive impairment).

MalaCards based summary : Boucher-Neuhauser Syndrome, also known as ataxia-hypogonadism-choroidal dystrophy syndrome, is related to gordon holmes syndrome and pnpla6-related disorders, and has symptoms including scanning speech, action tremor and cerebellar ataxia. An important gene associated with Boucher-Neuhauser Syndrome is PNPLA6 (Patatin Like Phospholipase Domain Containing 6), and among its related pathways/superpathways are Glycerophospholipid metabolism and ATP/ITP metabolism. Affiliated tissues include eye, cerebellum and retina, and related phenotypes are ataxia and chorioretinal dystrophy

Disease Ontology : 12 A syndrome characterized by spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy that has material basis in homozygous or compound heterozygous mutation in PNPLA6 on 19p13.2.

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1180DefinitionA very rare autosomal recessive, slowly progressive neurodegenerative disorder characterized by the triad of cerebellar ataxia (that generally manifests at adolescence or early adulthood), chorioretinal dystrophy, which may have a later onset (up to the fifth-sixth decade) leading to variable degrees of visual impairment, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Ataxia-hypogonadism-choroidal dystrophy syndrome belongs to a clinical continuum of neurodegenerative disorders along with the clinically overlapping cerebellar ataxia-hypogonadism syndrome (see this term).Visit the Orphanet disease page for more resources.

OMIM® : 57 Boucher-Neuhauser syndrome is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39; 612020) (summary by Synofzik et al., 2014). See also Gordon Holmes syndrome (GDHS; 212840), caused by mutation in the RNF216 gene (609948), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism. (215470) (Updated 05-Mar-2021)

KEGG : 36 Boucher-Neuhauser syndrome (BNS) is a rare syndrome characterized by the triad of early-onset autosomal-recessive cerebellar ataxia (ARCA), hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in BNS has been typically reported between the first and third decades of life; later ages of onset are rare. BNS has recently been linked to autosomal-recessive mutations in the PNPLA6 gene.

UniProtKB/Swiss-Prot : 73 Boucher-Neuhauser syndrome: An autosomal recessive disorder characterized by spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop 1 or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present.

Related Diseases for Boucher-Neuhauser Syndrome

Diseases related to Boucher-Neuhauser Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Related Disease Score Top Affiliating Genes
1 gordon holmes syndrome 31.1 RNF216 POLR3B POLR3A PNPLA6 OTUD4
2 pnpla6-related disorders 30.8 RNF216 PNPLA6
3 hypogonadism 30.3 POLR3B POLR3A PNPLA6
4 hypogonadotropic hypogonadism 30.2 POLR3B POLR3A PNPLA6
5 megalocornea-mental retardation syndrome 10.5
6 autosomal dominant cerebellar ataxia 10.4
7 autosomal recessive disease 10.3
8 amenorrhea 10.3
9 retinal degeneration 10.3
10 cerebellar degeneration 10.3
11 fundus dystrophy 10.3
12 inherited retinal disorder 10.3
13 retinitis pigmentosa 10.2
14 choroideremia 10.2
15 vitelliform macular dystrophy 10.2
16 neuroretinitis 10.2
17 hereditary spastic paraplegia 10.2
18 retinitis 10.2
19 movement disease 10.2
20 paraplegia 10.2
21 scotoma 10.2
22 pathologic nystagmus 10.2
23 hypoglycemia 10.2
24 spinocerebellar degeneration 10.2
25 ataxia and polyneuropathy, adult-onset 10.2
26 spastic ataxia 10.1 POLR3A PNPLA6
27 hypogonadotropic hypogonadism 7 with or without anosmia 10.0 POLR3B PNPLA6
28 normosmic congenital hypogonadotropic hypogonadism 10.0 POLR3B PNPLA6
29 spastic ataxia 4 10.0 POLR3B POLR3A
30 oliver-mcfarlane syndrome 10.0 PNPLA6 DENND4B
31 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 9.9 POLR3B POLR3A
32 polr3-related leukodystrophy 9.9 POLR3B POLR3A
33 spastic ataxia 8 9.9 POLR3B POLR3A
34 hypomyelinating leukoencephalopathy 9.9 POLR3B POLR3A
35 leukodystrophy, hypomyelinating, 10 9.9 POLR3B POLR3A
36 aicardi syndrome 9.9
37 mandibuloacral dysplasia progeroid syndrome 9.9
38 aphasia 9.9
39 apraxia 9.9
40 dementia 9.9
41 tuberous sclerosis 9.9
42 agnosia 9.9
43 cytokine deficiency 9.9
44 treacher collins syndrome 1 9.9 POLR3B POLR3A
45 hypomyelinating leukodystrophy 9.8 POLR3B POLR3A
46 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 9.8 POLR3B POLR3A PNPLA6
47 dystonia 11, myoclonic 9.8 POLR3B POLR3A
48 leukodystrophy 9.8 RNF216 POLR3B POLR3A
49 cerebral degeneration 9.7 POLR3B POLR3A
50 leukoencephalopathy with vanishing white matter 9.6 POLR3B POLR3A

Graphical network of the top 20 diseases related to Boucher-Neuhauser Syndrome:

Diseases related to Boucher-Neuhauser Syndrome

Symptoms & Phenotypes for Boucher-Neuhauser Syndrome

Human phenotypes related to Boucher-Neuhauser Syndrome:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 chorioretinal dystrophy 31 very rare (1%) HP:0001135
3 hypogonadotropic hypogonadism 31 very rare (1%) HP:0000044
4 abnormal upper motor neuron morphology 31 occasional (7.5%) HP:0002127
5 spasticity 31 very rare (1%) HP:0001257
6 intellectual disability, mild 31 very rare (1%) HP:0001256
7 gait ataxia 31 very rare (1%) HP:0002066
8 cerebellar atrophy 31 very rare (1%) HP:0001272
9 distal amyotrophy 31 very rare (1%) HP:0003693
10 photophobia 31 HP:0000613
11 progressive visual loss 31 HP:0000529
12 hypogonadotrophic hypogonadism 58 Very frequent (99-80%)
13 areflexia 31 HP:0001284
14 hyporeflexia 31 HP:0001265
15 scanning speech 31 HP:0002168
16 retinal dystrophy 31 HP:0000556
17 intention tremor 31 HP:0002080
18 congenital chorioretinal dystrophy 58 Very frequent (99-80%)
19 spinocerebellar atrophy 31 HP:0007263
20 decreased circulating gonadotropin level 31 HP:0030339

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Peripheral Nervous System:
sensorimotor axonal neuropathy (in some patients)

Endocrine Features:
hypogonadotropic hypogonadism
hypothalamic dysfunction
delay in secondary sexual characteristics

hypogonadism, hypogonadotropic

Laboratory Abnormalities:
decreased plasma gonadotrophin

Neurologic Central Nervous System:
cerebellar atrophy
scanning speech
intention tremor
cerebellar ataxia
spasticity (in some patients)
Head And Neck Eyes:
choroidal dystrophy (in most patients)
retinal dystrophy (in most patients)
visual loss, progressive (in most patients)
photophobia (in most patients)

Muscle Soft Tissue:
distal muscle wasting

Clinical features from OMIM®:

215470 (Updated 05-Mar-2021)

UMLS symptoms related to Boucher-Neuhauser Syndrome:

scanning speech, action tremor, cerebellar ataxia

Drugs & Therapeutics for Boucher-Neuhauser Syndrome

Genetic Tests for Boucher-Neuhauser Syndrome

Genetic tests related to Boucher-Neuhauser Syndrome:

# Genetic test Affiliating Genes
1 Ataxia-Hypogonadism-Choroidal Dystrophy Syndrome 29 PNPLA6

Anatomical Context for Boucher-Neuhauser Syndrome

MalaCards organs/tissues related to Boucher-Neuhauser Syndrome:

Eye, Cerebellum, Retina, Pituitary

Publications for Boucher-Neuhauser Syndrome

Articles related to Boucher-Neuhauser Syndrome:

(show all 18)
# Title Authors PMID Year
Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. 6 57
25033069 2014
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. 57 6
24355708 2014
Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhäuser syndrome. 57 6
9321767 1997
Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. 57
7639308 1995
A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhäuser syndrome). 57
1906382 1991
Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhäuser syndrome) 57
2801777 1989
Syndrome of cerebellar ataxia and hypogonadotrophic hypogonadism: evidence for pituitary gonadotrophin deficiency. 57
2494301 1989
Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism. 57
1149314 1975
Familial ataxia, hypogonadism and retinal degeneration. 57
5806782 1969
Severe chorioretinal atrophy in Boucher-Neuhauser syndrome. 61
31712030 2020
Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies. 61
27512013 2017
The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview. 61
25413954 2015
The gonadotropin-releasing hormone type I receptor is expressed in the mouse cerebellum. 61
18592335 2008
[Hypogonadotropic hypogonadism discovered in a patient with cerebellar ataxia]. 61
16357818 2005
Prominent expression of spinocerebellar ataxia type-1 (SCA1) gene encoding ataxin-1 in LH-producing cells, LbetaT2. 61
15514462 2004
[Significance of neuroimaging in the diagnosis of Boucher-Neuhauser syndrome]. 61
12868401 2003
Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new variant of Boucher-Neuhauser syndrome? 61
12525550 2003
Boucher-Neuhauser syndrome associated with hypocalciuric hypercalcemia. 61
7718973 1995

Variations for Boucher-Neuhauser Syndrome

ClinVar genetic disease variations for Boucher-Neuhauser Syndrome:

# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PNPLA6 NM_001166114.2(PNPLA6):c.3143C>T (p.Thr1048Ile) SNV Pathogenic 101039 rs587777181 19:7621388-7621388 19:7556502-7556502
2 PNPLA6 NM_001166114.2(PNPLA6):c.2185-1G>C SNV Pathogenic 101040 rs606231249 19:7616247-7616247 19:7551361-7551361
3 PNPLA6 NM_001166114.2(PNPLA6):c.3298G>A (p.Val1100Met) SNV Pathogenic 101041 rs587777182 19:7622071-7622071 19:7557185-7557185
4 PNPLA6 NM_001166114.2(PNPLA6):c.3167T>C (p.Phe1056Ser) SNV Pathogenic 101042 rs587777183 19:7621412-7621412 19:7556526-7556526
5 PNPLA6 NM_001166114.2(PNPLA6):c.1243dup (p.Asp415fs) Duplication Pathogenic 156538 rs587777853 19:7606940-7606941 19:7542054-7542055
6 PNPLA6 NM_001166114.2(PNPLA6):c.3409C>T (p.Arg1137Cys) SNV Pathogenic 156539 rs587777854 19:7623747-7623747 19:7558861-7558861
7 PNPLA6 NM_001166114.2(PNPLA6):c.3356G>T (p.Gly1119Val) SNV Pathogenic 430847 rs1555751016 19:7622129-7622129 19:7557243-7557243
8 PNPLA6 NM_001166114.2(PNPLA6):c.1705G>T (p.Gly569Trp) SNV Pathogenic 143933 rs587777615 19:7614889-7614889 19:7550003-7550003
9 PNPLA6 NM_001166114.2(PNPLA6):c.1492G>A (p.Ala498Thr) SNV Uncertain significance 547855 rs375397452 19:7607776-7607776 19:7542890-7542890
10 PNPLA6 NM_001166114.2(PNPLA6):c.3095G>C (p.Ser1032Thr) SNV Uncertain significance 240694 rs377449787 19:7621340-7621340 19:7556454-7556454

UniProtKB/Swiss-Prot genetic disease variations for Boucher-Neuhauser Syndrome:

# Symbol AA change Variation ID SNP ID
1 PNPLA6 p.Gly578Trp VAR_071092 rs587777615
2 PNPLA6 p.Ser1045Leu VAR_071094 rs541098659
3 PNPLA6 p.Thr1058Ile VAR_071095 rs587777181
4 PNPLA6 p.Phe1066Ser VAR_071096 rs587777183
5 PNPLA6 p.Val1110Met VAR_071098 rs587777182
6 PNPLA6 p.Pro1122Leu VAR_071099 rs748506175
7 PNPLA6 p.Arg1147Cys VAR_073412 rs587777854
8 PNPLA6 p.Ser1175Cys VAR_073413 rs155575159
9 PNPLA6 p.Arg1359Trp VAR_073416 rs374434303

Expression for Boucher-Neuhauser Syndrome

Search GEO for disease gene expression data for Boucher-Neuhauser Syndrome.

Pathways for Boucher-Neuhauser Syndrome

Pathways related to Boucher-Neuhauser Syndrome according to KEGG:

# Name Kegg Source Accession
1 Glycerophospholipid metabolism hsa00564

Pathways related to Boucher-Neuhauser Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.55 POLR3B POLR3A

GO Terms for Boucher-Neuhauser Syndrome

Cellular components related to Boucher-Neuhauser Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.23 SNX14 RNF216 POLR3B POLR3A PNPLA6 OTUD4
2 RNA polymerase III complex GO:0005666 8.96 POLR3B POLR3A

Biological processes related to Boucher-Neuhauser Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription, DNA-templated GO:0006351 9.16 POLR3B POLR3A
2 positive regulation of type I interferon production GO:0032481 8.96 POLR3B POLR3A
3 positive regulation of interferon-beta production GO:0032728 8.62 POLR3B POLR3A

Molecular functions related to Boucher-Neuhauser Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotidyltransferase activity GO:0016779 8.96 POLR3B POLR3A
2 DNA-directed 5'-3' RNA polymerase activity GO:0003899 8.62 POLR3B POLR3A

Sources for Boucher-Neuhauser Syndrome

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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