Features of BBSOAS
The phenotypic spectrum of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is broad and variable, but the most well-established characteristics include developmental delay/intellectual disability and visual impairment (including optic nerve atrophy, optic nerve hypoplasia, and cortical visual impairment). Other common features include hypotonia, oromotor dysfunction, mild and inconsistent dysmorphic facial features. Morphological changes of brain structures including thinning of the corpus callosum, and autism spectrum disorder are also considered common. Individuals are at an elevated risk of seizures, including infantile spasms.
Genotype-phenotype correlations have been proposed, with individuals with mutations in the DBD typically showing a more severe phenotype, and individuals with whole-gene deletions and truncating mutations tending to have moderate to mild symptoms. Individuals with point mutations outside of the DBD most often manifest the mildest phenotype.
BBSOAS is considered a static encephalopathy and has not been shown to be progressive/degenerative. There is no progression of the eye phenotype known, including no known progression of optic atrophy.
- 89% speech delay, vision impairment, and hypotonia
- 80% Autism Spectrum Disorder (ASD) or features thereof
- 78% cognitive/ behavioral anomalies
- 52% seizures including infantile spasms
- 70-78% feeding difficulties including oromotor dysfunction
- 84% mouth-stuffing
- 82% optic atrophy or optic disc pallor
- 49% optic nerve hypoplasia or a small optic nerve
- 68% Cortical Visual Impairment (CVI) (),
- 52% manifest latent nystagmus/fusion maldevelopment
- 78% Alacrima (reduced or absent tear production)
- 33% abnormal hearing
*Behavioral Features, parent reported:
- 100% a love of music
- 76% an unusually good long-term memory
- 78% a high pain tolerance
- 61% sleep difficulties
- 59% touch sensitivity
*Sample of 54 patients in 2019. The clinical features of BBSOAS are variable, and not every individual manifests all features necessarily.
BBSOAS is an autosomal dominant disorder. The majority of cases are de novo, but familial cases are also known. The chance of unaffected parents with one affected child having a second affected child is less than 3%, while the chance of an affected parent having an affected child is 50%.
BBSOAS is diagnosed by a geneticist through either chromosome microarray, whole exome sequencing, or NR2F1 sequencing.
Recommended testing following a BBSOAS diagnosis
- A developmental assessment to identify areas of impairment and allow for early intervention
- A comprehensive psychological evaluation for ASD; ADI-R and ADOS testing performed by a certified clinical psychologist
- Brain MRI, recommended at age three years or older
- Full, dilated eye examination by an ophthalmologist every two years
- Full hearing evaluation every two years
Clinical course over time
BBSOAS is a neurodevelopmental disorder, which is present at the time of birth and has the course of a static encephalopathy. Most individuals with BBSOAS will require intensive therapies throughout their lifetime. They will continue to make progress, and they will reach many milestones, but the expected functioning level is still in the intellectual disability range. Some individuals with BBSOAS live semi-independently, some have become parents. The majority of individuals with BBSOAS will still require assistance and much support when they are grown up to be adults. There is no major limitation to life expectancy in individuals with BBSOAS.
Currently, there is no cure to treat BBSOAS. However, with early intervention and proper management, much can be done to improve the skill sets and quality of life of people living with BBSOAS.
Chen, C.-A. et al. The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype–phenotype correlations. Genet. Med. 18, 1143–1150 (2016).
Rech ME et al. Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations. Am J Med Genet A. 2020;182(6):1426-1437. doi:10.1002/ajmg.a.61580 Epub 2020 Apr 10
US Food and Drug Administration’s Definition of Disease Prevalence for Therapies Qualifying Under Orphan Drug Act. https://www.ecfr.gov/cgibin/retrieveECFR?gp=&SID=91b7be5e87481538e33a4c0a76ba7183&n=184.108.40.206.6.3%20&r=SUBPART&ty=HTML.
United States Census Bureau. Quick Facts. https://www.census.gov/quickfacts/fact/table/US/PST045219.
Orphanet. About Rare Diseases. https://www.orpha.net/consor/cgi-bin/Education_AboutRareDiseases.php?lng=EN.