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Bosch-Boonstra-Schaaf optic atrophy syndrome(BBSOAS)

MedGen UID:
816693
Concept ID:
C3810363
Disease or Syndrome
Synonym: BBSOAS
SNOMED CT: Bosch Boonstra Schaaf optic atrophy syndrome (770723007); BBSOAS - Bosch Boonstra Schaaf optic atrophy syndrome (770723007); Optic atrophy, intellectual disability syndrome (770723007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): NR2F1 (5q15)
 
Monarch Initiative: MONDO:0014320
OMIM®: 615722
Orphanet: ORPHA401777

Definition

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disorder characterized by delayed development, moderately impaired intellectual development, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by Bosch et al., 2014). [from OMIM]

Clinical features

From HPO
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Prominent antihelix
MedGen UID:
335147
Concept ID:
C1845272
Finding
The presence of an abnormally prominent antihelix.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Uplifted earlobe
MedGen UID:
344655
Concept ID:
C1856117
Anatomical Abnormality
An abnormal orientation of the earlobes such that they point out- and upward. That is, the lateral surface of ear lobe faces superiorly.
Darwin tubercle of helix
MedGen UID:
866825
Concept ID:
C4021179
Anatomical Abnormality
Small expansion of the helical fold at the junction of the superior and descending portions of the helix.
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Compulsive behaviors
MedGen UID:
109373
Concept ID:
C0600104
Mental or Behavioral Dysfunction
Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Pointed chin
MedGen UID:
336193
Concept ID:
C1844505
Finding
A marked tapering of the lower face to the chin.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Slow-growing hair
MedGen UID:
371309
Concept ID:
C1832348
Finding
Hair whose growth is slower than normal.
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Visual field defect
MedGen UID:
854603
Concept ID:
C3887875
Finding
An absolute or relative reduction in the extent of the normal field of vision.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBosch-Boonstra-Schaaf optic atrophy syndrome
Follow this link to review classifications for Bosch-Boonstra-Schaaf optic atrophy syndrome in Orphanet.

Professional guidelines

PubMed

Rech ME, McCarthy JM, Chen CA, Edmond JC, Shah VS, Bosch DGM, Berry GT, Williams L, Madan-Khetarpal S, Niyazov D, Shaw-Smith C, Kovar EM, Lupo PJ, Schaaf CP
Am J Med Genet A 2020 Jun;182(6):1426-1437. Epub 2020 Apr 10 doi: 10.1002/ajmg.a.61580. PMID: 32275123
Chen CA, Bosch DG, Cho MT, Rosenfeld JA, Shinawi M, Lewis RA, Mann J, Jayakar P, Payne K, Walsh L, Moss T, Schreiber A, Schoonveld C, Monaghan KG, Elmslie F, Douglas G, Boonstra FN, Millan F, Cremers FP, McKnight D, Richard G, Juusola J, Kendall F, Ramsey K, Anyane-Yeboa K, Malkin E, Chung WK, Niyazov D, Pascual JM, Walkiewicz M, Veluchamy V, Li C, Hisama FM, de Vries BB, Schaaf C
Genet Med 2016 Nov;18(11):1143-1150. Epub 2016 Mar 17 doi: 10.1038/gim.2016.18. PMID: 26986877

Recent clinical studies

Etiology

Kocaaga A, Yimenicioglu S, Gürsoy HH
Indian J Ophthalmol 2022 Jul;70(7):2762-2764. doi: 10.4103/ijo.IJO_1061_22. PMID: 35791240Free PMC Article
Billiet B, Amati-Bonneau P, Desquiret-Dumas V, Guehlouz K, Milea D, Gohier P, Lenaers G, Mirebeau-Prunier D, den Dunnen JT, Reynier P, Ferré M
Hum Mutat 2022 Feb;43(2):128-142. Epub 2021 Dec 9 doi: 10.1002/humu.24305. PMID: 34837429
Gazdagh G, Mawby R, Self JE, Baralle D; Deciphering Developmental Disorders Study
Am J Med Genet A 2022 Mar;188(3):900-906. Epub 2021 Nov 17 doi: 10.1002/ajmg.a.62569. PMID: 34787370
Hobbs MM, Wolters WC, Rayapati AO
J Psychiatr Pract 2020 Jan;26(1):58-62. doi: 10.1097/PRA.0000000000000440. PMID: 31913971
Bojanek EK, Mosconi MW, Guter S, Betancur C, Macmillan C, Cook EH
Am J Med Genet A 2020 Jan;182(1):213-218. Epub 2019 Nov 15 doi: 10.1002/ajmg.a.61409. PMID: 31729143Free PMC Article

Diagnosis

Desai NK, Kralik SF, Edmond JC, Shah V, Huisman TAGM, Rech M, Schaaf CP
AJNR Am J Neuroradiol 2023 Feb;44(2):212-217. Epub 2023 Jan 26 doi: 10.3174/ajnr.A7758. PMID: 36702506Free PMC Article
Billiet B, Amati-Bonneau P, Desquiret-Dumas V, Guehlouz K, Milea D, Gohier P, Lenaers G, Mirebeau-Prunier D, den Dunnen JT, Reynier P, Ferré M
Hum Mutat 2022 Feb;43(2):128-142. Epub 2021 Dec 9 doi: 10.1002/humu.24305. PMID: 34837429
Kingrey B, Phornphutkul C, Chen W
J AAPOS 2021 Oct;25(5):314-316. Epub 2021 Aug 20 doi: 10.1016/j.jaapos.2021.05.007. PMID: 34425235
Jezela-Stanek A, Ciara E, Jurkiewicz D, Kucharczyk M, Jędrzejowska M, Chrzanowska KH, Krajewska-Walasek M, Żemojtel T
Mol Genet Genomic Med 2020 Sep;8(9):e1263. Epub 2020 Apr 26 doi: 10.1002/mgg3.1263. PMID: 32337850Free PMC Article
Rech ME, McCarthy JM, Chen CA, Edmond JC, Shah VS, Bosch DGM, Berry GT, Williams L, Madan-Khetarpal S, Niyazov D, Shaw-Smith C, Kovar EM, Lupo PJ, Schaaf CP
Am J Med Genet A 2020 Jun;182(6):1426-1437. Epub 2020 Apr 10 doi: 10.1002/ajmg.a.61580. PMID: 32275123

Prognosis

Kocaaga A, Yimenicioglu S, Gürsoy HH
Indian J Ophthalmol 2022 Jul;70(7):2762-2764. doi: 10.4103/ijo.IJO_1061_22. PMID: 35791240Free PMC Article
Mio C, Fogolari F, Pezzoli L, D'Elia AV, Iascone M, Damante G
Mol Genet Genomic Med 2020 Jul;8(7):e1278. Epub 2020 May 15 doi: 10.1002/mgg3.1278. PMID: 32412696Free PMC Article
Park SE, Lee JS, Lee ST, Kim HY, Han SH, Han J
Ophthalmic Genet 2019 Aug;40(4):359-361. Epub 2019 Aug 8 doi: 10.1080/13816810.2019.1650074. PMID: 31393201
Bertacchi M, Parisot J, Studer M
Brain Res 2019 Feb 15;1705:75-94. Epub 2018 Apr 27 doi: 10.1016/j.brainres.2018.04.024. PMID: 29709504

Clinical prediction guides

Kocaaga A, Yimenicioglu S, Gürsoy HH
Indian J Ophthalmol 2022 Jul;70(7):2762-2764. doi: 10.4103/ijo.IJO_1061_22. PMID: 35791240Free PMC Article
Gazdagh G, Mawby R, Self JE, Baralle D; Deciphering Developmental Disorders Study
Am J Med Genet A 2022 Mar;188(3):900-906. Epub 2021 Nov 17 doi: 10.1002/ajmg.a.62569. PMID: 34787370
Mio C, Fogolari F, Pezzoli L, D'Elia AV, Iascone M, Damante G
Mol Genet Genomic Med 2020 Jul;8(7):e1278. Epub 2020 May 15 doi: 10.1002/mgg3.1278. PMID: 32412696Free PMC Article
Park SE, Lee JS, Lee ST, Kim HY, Han SH, Han J
Ophthalmic Genet 2019 Aug;40(4):359-361. Epub 2019 Aug 8 doi: 10.1080/13816810.2019.1650074. PMID: 31393201
Bertacchi M, Parisot J, Studer M
Brain Res 2019 Feb 15;1705:75-94. Epub 2018 Apr 27 doi: 10.1016/j.brainres.2018.04.024. PMID: 29709504

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