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Boucher Neuhauser syndrome(BNHS)

MedGen UID:
347798
Concept ID:
C1859093
Disease or Syndrome
Synonyms: BNHS; Chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Cerebellar ataxia with hypogonadism and choroidal dystrophy syndrome (715984007); Boucher Neuhäuser syndrome (715984007)
 
Gene (location): PNPLA6 (19p13.2)
OMIM®: 215470
Orphanet: ORPHA1180

Disease characteristics

Excerpted from the GeneReview: PNPLA6-Related Disorders
PNPLA6-related disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia, upper motor neuron involvement manifesting as spasticity and/or brisk reflexes, chorioretinal dystrophy associated with variable degrees of reduced visual function, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics), either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting), hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia), short stature, and impaired cognitive functioning (learning disabilities in children and deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia). [from GeneReviews]
Authors:
Matthis Synofzik  |  Robert B Hufnagel  |  Stephan Züchner   view full author information

Additional descriptions

From OMIM
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.  http://www.omim.org/entry/215470
From GHR
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).  https://ghr.nlm.nih.gov/condition/boucher-neuhauser-syndrome

Clinical features

Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Abnormal sensitivity to light. This may occur as a manifestation of EYE DISEASES; MIGRAINE; SUBARACHNOID HEMORRHAGE; MENINGITIS; and other disorders. Photophobia may also occur in association with DEPRESSION and other MENTAL DISORDERS.
Spinocerebellar atrophy
MedGen UID:
39733
Concept ID:
C0087012
Disease or Syndrome
A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
A finding indicating the complete absence of neurological reflexes.
Hypogonadotropic hypogonadism 7 with or without anosmia
MedGen UID:
87440
Concept ID:
C0342384
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
Scanning speech
MedGen UID:
637120
Concept ID:
C0522198
Mental or Behavioral Dysfunction
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Chorioretinal dystrophy
MedGen UID:
346626
Concept ID:
C1857627
Disease or Syndrome
Progressive visual loss
MedGen UID:
479327
Concept ID:
C3277697
Finding
A reduction of previously attained ability to see.
Intention tremor
MedGen UID:
892758
Concept ID:
C4020856
Finding
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Cerebellar atrophy
MedGen UID:
892891
Concept ID:
C4020873
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBoucher Neuhauser syndrome
Follow this link to review classifications for Boucher Neuhauser syndrome in Orphanet.

Recent clinical studies

Diagnosis

Langdahl JH, Frederiksen AL, Nguyen N, Brusgaard K, Juhl CB
Eur J Med Genet 2017 Feb;60(2):105-109. Epub 2016 Nov 16 doi: 10.1016/j.ejmg.2016.11.003. PMID: 27866050
Koh K, Kobayashi F, Miwa M, Shindo K, Isozaki E, Ishiura H, Tsuji S, Takiyama Y
J Hum Genet 2015 Apr;60(4):217-20. Epub 2015 Jan 29 doi: 10.1038/jhg.2015.3. PMID: 25631098
Kate MP, Kesavadas C, Nair M, Krishnan S, Soman M, Singh A
J Neurol Neurosurg Psychiatry 2011 Aug;82(8):888-91. Epub 2010 Jun 28 doi: 10.1136/jnnp.2009.196790. PMID: 20587490
Umehara T, Yaguchi H, Suzuki M, Isozaki E, Mochio S
J Neurol Sci 2010 Aug 15;295(1-2):128-30. Epub 2010 Jun 4 doi: 10.1016/j.jns.2010.05.005. PMID: 20605169
Yu SI, Kim JL, Lee SG, Kim HW, Kim SJ
Korean J Ophthalmol 2008 Dec;22(4):263-7. doi: 10.3341/kjo.2008.22.4.263. PMID: 19096246Free PMC Article

Therapy

Richards MR, Plummer L, Chan YM, Lippincott MF, Quinton R, Kumanov P, Seminara SB
J Med Genet 2017 Jan;54(1):19-25. Epub 2016 Aug 10 doi: 10.1136/jmedgenet-2016-104064. PMID: 27512013Free PMC Article

Clinical prediction guides

Garcia-Cazorla À, Mochel F, Lamari F, Saudubray JM
J Inherit Metab Dis 2015 Jan;38(1):19-40. Epub 2014 Nov 21 doi: 10.1007/s10545-014-9776-6. PMID: 25413954
Yu SI, Kim JL, Lee SG, Kim HW, Kim SJ
Korean J Ophthalmol 2008 Dec;22(4):263-7. doi: 10.3341/kjo.2008.22.4.263. PMID: 19096246Free PMC Article

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