Bosma arhinia microphthalmia syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Bosma arhinia microphthalmia syndrome (BAMS) is a rare condition characterized by abnormalities of the nose and eyes and problems with puberty.

The key feature of BAMS is arhinia, which is the absence of an external nose. While most people with BAMS are born without a nose, some affected individuals have a severely underdeveloped (hypoplastic) nose. Affected individuals may also be missing the brain structure involved in the sense of smell (olfactory bulb). Because of these abnormalities, people with BAMS have an impaired ability to smell and, consequently, to taste.

In most people with BAMS, the eyeballs are abnormally small (microphthalmia) or absent (anophthalmia), which causes severe vision impairment or blindness. Additional eye abnormalities common in BAMS include a gap or hole in one of several structures of the eye (coloboma) and clouding of the lenses of the eyes (cataracts).

Additional head and face abnormalities that can occur in people with BAMS include a high arch or opening in the roof of the mouth (high-arched or cleft palate), absence of the sinuses behind the nose (paranasal sinuses), blockage of the nasal passages (choanal atresia), narrowing of the tear ducts (nasolacrimal duct stenosis), or a small upper jaw (hypoplastic maxilla). Many of these abnormalities contribute to difficulty breathing, particularly in affected babies. Some affected individuals have abnormal external ears.

Individuals with BAMS also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, these hormone problems often result in delayed puberty. Affected males may also have underdeveloped reproductive tissues and undescended testes (cryptorchidism).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

BAMS is usually caused by mutations in the SMCHD1 gene. Other, unknown genes may be rare causes of the condition.

The SMCHD1 gene provides instructions for making a protein involved in regulating gene activity by altering the structure of DNA. Specifically, the SMCHD1 protein plays a role in turning off (silencing) certain genes. Among other functions, the SMCHD1 protein appears to be important for development of the nose, eyes, and other structures of the head and face.

Researchers are unsure how SMCHD1 gene mutations affect the protein's function and lead to the development problems characteristic of BAMS. Changes in this gene may lead to abnormal silencing of genes involved in development of the head and face, which could underlie arhinia, microphthalmia, and other characteristic facial abnormalities of BAMS. Problems with nasal development may affect gonadotropin-releasing hormone (GnRH) neurons, which are nerve cells that control the release of reproductive hormones. GnRH neurons originate in the developing nose and then move to the brain. Impaired development of these neurons could explain hypogonadotropic hypogonadism in affected individuals.

Some people with an SMCHD1 gene mutation have arhinia without other features of BAMS (isolated arhinia) or less severe abnormalities of the nose, leading researchers to suspect that additional genetic factors contribute to the severity of the symptoms. These additional factors are not yet known.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered SMCHD1 gene in each cell is sufficient to cause the disorder.

Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In some cases, an affected person inherits the mutation from one affected parent. The parent often has milder symptoms, such as a reduced sense of smell (anosmia), arhinia without other features of BAMS, or less severe abnormalities of the nose.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

BAMS is a very rare condition with an unknown prevalence. Fewer than 100 cases of the condition have been described in the medical literature. BAMS has been found in several different populations.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal midface morphology · Very frequent (99-80%)

An anomaly of the midface, which is a region and not an anatomical term. It extends, superiorly, from the inferior orbital margin to, inferiorly, the level of nasal base. It is formed by the maxilla (upper jaw) and zygoma and cheeks and malar region. Traditionally, the nose and premaxilla are not included in the midface.

Absent nares · Very frequent (99-80%)

The nostrils (the paired channels of the nose) are not present.

Anosmia · Very frequent (99-80%)

An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.

Aplasia of the nose · Very frequent (99-80%)

Complete absence of all nasal structures.

Cataract · Very frequent (99-80%)

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

External genital hypoplasia · Very frequent (99-80%)

Underdevelopment of part or all of the external reproductive organs.

Failure of eruption of permanent teeth · Very frequent (99-80%)

Lack of tooth eruption of the secondary dentition.

Hypogonadism · Very frequent (99-80%)

A decreased functionality of the gonad.

Other findings in the same source

From: Orphanet

Additional reported features include Hypoplasia of the olfactory bulb (Very frequent (99-80%)); Hyposmia (Very frequent (99-80%)); Inguinal hernia (Very frequent (99-80%)); Single naris (Very frequent (99-80%)); Tooth malposition (Very frequent (99-80%)); Hypoplasia of penis (Very frequent (99-80%)); Abdominal wall muscle weakness (Frequent (79-30%)); Amblyopia (Frequent (79-30%)); Anophthalmia (Frequent (79-30%)); Aplasia/Hypoplasia involving the nose (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Bosma arhinia microphthalmia syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.