What is Bosma Arhinia Microphthalmia Syndrome?

History
Cause and symptoms
SMCHD1 gene
Epidemiology
Diagnosis and treatment
References
Further reading 

Bosma arhinia microphthalmia syndrome or BAMS is an extremely rare condition associated with facial abnormalities, mainly of the nose and the eye. Mutations in the SMCHD1 gene are the most common cause of BAMS.

Less than 100 patients have been reported worldwide in the last century. The most prominent feature of the syndrome is the absence of a nose, as well as hypoplasia of the nose in some cases. As a result, olfactory and gustatory sensations are weakened.

History

In 1972, Gifford et al. reported the surgical reconstruction of his first two unrelated male patients with this unusual craniofacial abnormality. Later, in 1981, Bosma et al. published the same two instances, defining the malformation pattern that currently bears his name. These patients had hypoplasia of the eyes, sensory abnormalities of taste and smell, decreased eyesight with cataracts and colobomata, and hypogonadotropic hypogonadism, according to him.

Cause and symptoms

Mutations in the SMCHD1 (Structural maintenance of chromosomes flexible hinge domain containing 1) gene cause BAMS. Other unknown genes may also play a role in the condition's occurrence. This condition has an autosomal dominant inheritance pattern.

BAMS is characterized by nasal and ocular abnormalities, along with puberty dysfunctions. Patients with BAM syndrome may also develop microphthalmia or anophthalmia, which can result in significant vision impairment or blindness. Colobamas and cataracts are two more eye abnormalities that can occur.

BAMS is characterized by arhinia, or the lack of an external nose. While the majority of patients with BAMS are born without a nose, some have a severely underdeveloped nose (hypoplastic). Affected people may also lack an olfactory bulb that controls their sense of smell. Due to these anomalies, people with BAMS have a reduced capacity to smell and, as a result, taste. Many of these anomalies contribute to breathing problems, especially in neonates.

Some people with this condition have abnormal external ears. A high arch or cleft palate, lack of the sinuses behind the nose (choanal atresia), and narrowing of the tear ducts are other head and face anomalies that can develop in patients with BAMS.

Individuals with this syndrome also experience hypogonadotropic hypogonadism, which causes a reduction in the synthesis of hormones that affect sexual development directly. This leads to delayed puberty if no endocrinological treatment is used. Affected males may also have cryptorchidism and undeveloped reproductive organs.

SMCHD1 gene

The SMCHD1 gene gives instructions for creating a protein that regulates gene activity by changing DNA structure. The SMCHD1 protein, in particular, is involved in turning off or silencing certain genes. The SMCHD1 protein appears to be critical for the development of the nose, eyes, and other head and face features.

Changes in this gene may induce aberrant facial and head development, as well as an effect on gonadotropic releasing hormone (GnRH), which could explain hypogonadotropic hypogonadism in BAMS patients.

Some patients with an SMCHD1 gene mutation have arhinia but no other BAMS symptoms (isolated arhinia) or less severe nasal abnormalities, prompting researchers to believe that other genetic factors contribute to the severity of the symptoms. These other parameters are unknown at this time and are currently being investigated.

Epidemiology

BAMS is an extremely rare disease with an unknown prevalence. In the medical literature, there are just about 100 cases of the condition. BAMS has been discovered in a diverse group of people, including Asians and Hispanics.

Diagnosis and treatment

BAMS is diagnosed at birth mainly based on physical examination and molecular genetic testing of the SMCHD1 gene. Because of breathing and feeding difficulties, children with BAMS may require urgent medical care early in life. They do, however, usually grow up to be healthy, productive people with a regular life span. Many structural problems, such as cleft palate, can be rectified surgically.

For the majority of patients, continuous medical care will be required to manage additional symptoms. Affected individuals and their families may benefit from psychosocial support and genetic counseling. As BAMS is extremely rare, there are no defined treatment protocols or guidelines for those who are affected.

References

• Arhinia, M., & Hypogonadism, H. (2021). BOSMA ARHINIA MICROPHTHALMIA SYNDROME. Smith's Recognizable Patterns of Human Malformation-E-Book, 346.
• Trivedi, A., Bean, T., Brown, K., & Cain, C. (2020). Bosma Arhinia Microphthalmia and Cardiac Abnor-malities: A Case Report. Clin Med Rev Case Rep, 7, 311. https://doi.org/10.23937/2378-3656/1410311
• Bansal, S., Sharma, R., & Jangid, N. Bosma Arhinia Microphthalmia Syndrome [BAMS]: A Case Report. http://www.rmjonline.in/sites/default/files/2021-07/case_rep_03.pdf
• Shaw, N. D., Brand, H., Kupchinsky, Z. A., Bengani, H., Plummer, L., Jones, T. I., Erdin, S., Williamson, K. A., Rainger, J., Stortchevoi, A., Samocha, K., Currall, B. B., Dunican, D. S., Collins, R. L., Willer, J. R., Lek, A., Lek, M., Nassan, M., Pereira, S., Kammin, T., … Talkowski, M. E. (2017). SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nature Genetics, 49(2), 238–248. https://doi.org/10.1038/ng.3743
• Brasseur, B., Martin, C. M., Cayci, Z., Burmeister, L., & Schimmenti, L. A. (2016). Bosma arhinia microphthalmia syndrome: Clinical report and review of the literature. American Journal of Medical Genetics. Part A, 170A(5), 1302–1307. https://doi.org/10.1002/ajmg.a.37572
• Bosma arhinia microphthalmia syndrome. [Online] MedlinePlus. Available at: https://medlineplus.gov/genetics/condition/bosma-arhinia-microphthalmia-syndrome/
• BOSMA ARHINIA MICROPHTHALMIA SYNDROME; BAMS. [Online] OMIM. Available at: https://www.omim.org/entry/603457
• Bosma Arhinia Microphthalmia Syndrome. [Online] National organization for rare disorders. Available at: https://rarediseases.org/rare-diseases/bosma-arhinia-microphthalmia-syndrome/

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