Introduction

Anosmia is the complete loss of smell, and is termed congenital anosmia when this inability to smell is present from birth. Congenital anosmia is generally linked to genetic or developmental abnormalities; on the other hand, acquired anosmia can be due to infections, trauma, or neurological issues.¹ 

The impact of anosmia is often underestimated, as one’s sense of smell is crucial in detecting hazards (gas leaks and smoke), the formation of memories, and recognition of food flavours. Congenital anosmia is often underdiagnosed in infants and children, as it may be misattributed to picky eating. It is important to understand congenital anosmia to improve diagnosis techniques and enhance the general quality of life in individuals.

Clinical features

Primary symptoms

Congenital anosmia is when an individual is completely unable to perceive odours. Unlike gradually losing smell or temporarily experiencing a loss of smell, this is a generally non-progressive, lifelong condition. This symptom usually goes unnoticed in the early stages of life, as babies and infants cannot articulate their sensory issues. Parents may also be unable to recognise these issues unless they become apparent in situations.

Associated features

Despite the loss of smell being quite difficult to pinpoint, this sensory inability can indirectly affect other senses, such as taste. Flavour recognition relies heavily on the olfactory system, so individuals with congenital anosmia often have issues with recognising food taste.⁶ In children, this can be misinterpreted as picky eating, but they typically have a reduced appetite and fussiness with food. This can continue to affect the nutrition of an individual.² 

Age of onset and diagnosis

Congenital anosmia is present from birth; however remains underdiagnosed in newborns and infants. Therefore, diagnosis is often delayed until childhood and adolescence. Congenital anosmia is often made apparent when children fail smell-based screening tests or similar medical evaluations. Sometimes children become aware of not being able to detect smells by themselves, and this can lead to a diagnosis. Early detection is essential for providing appropriate support and safety measures.¹

Diagnostic evaluation

Patient history and symptom review

The first step in diagnosing congenital anosmia involves a full patient history review. Key features include the absence of smell since birth, with no prior period of normal olfactory function. Other causes, such as trauma to the head, respiratory infections, or toxin exposure, should also be ruled out as they generally reflect acquired anosmia.² With there being a lack of these contributing factors, it increases the likelihood of the condition being of a congenital origin.

Olfactory testing

When it comes to testing olfactory function, standardised smell identification tests are used. The most common one is the University of Pennsylvania Smell Identification Test (UPSIT), as this measures if an individual is able to identify a variety of common odors. These assessments can help confirm the severity and presence of anosmia and distinguish between partial of complete loss of smell.³

Imaging studies

An important part of the diagnostic procedure is brain magnetic resonance imaging (MRI). It allows the visualisation of the olfactory bulbs and tracts in great detail, which are frequently absent or underdeveloped in congenital anosmia.² Any structural abnormalities in the brain that might be connected to syndromic variants of the disorder can also be found with the aid of an MRI.

Differential diagnosis

Distinguishing acquired anosmia from congenital variants is essential. Trauma, infections (including viral upper respiratory infections), chronic sinusitis, and neurological illnesses like Parkinson's or Alzheimer's can all cause acquired anosmia. A thorough assessment of the imaging results, clinical history, and symptom start aids in ruling out these potential causes and confirming the diagnosis of congenital anosmia.³

Genetic causes

Isolated congenital anosmia

Congenital anosmia can occur as an isolated condition without other physical or developmental abnormalities in some individuals. This non-syndromic form is often sporadic, although familial cases have been reported. Research has shown that there are several genetic mutations that are associated with isolated congenital anosmia, mainly in genes involved in the development and function of the olfactory system. There are mutations in the PROKR2 and PROK2 genes, which play important roles in olfactory bulb formation and signaling and have been implicated in some cases.⁵

Syndromic congenital anosmia

Congenital anosmia more frequently occurs as a component of a larger genetic disease. Kallmann syndrome, which combines anosmia with hypogonadotropic hypogonadism (delayed or non-existent puberty resulting from a deficit in gonadotropin-releasing hormone), is one of the most well-known. Mutations in several genes, including KAL1, FGFR1, and CHD7, which are all involved in the migration of neurons that make up the reproductive and olfactory systems, have been connected to Kallmann syndrome.⁴

CHARGE syndrome involves heart issues, growth retardation, genital anomalies, and ear abnormalities, and coloboma is also considered as a syndromic cause. Another syndromic cause, which is characterised by obesity, polydactyly, retinal degeneration, renal abnormalities, and cognitive impairment, are indicators of Bardet-Biedl syndrome. Because of underlying developmental abnormalities, anosmia may be a feature of the clinical presentation in both situations.³

Inheritance patterns

The genetic pattern of congenital anosmia is dependent on the type of the specific condition. In isolated forms, the inheritance pattern can be autosomal dominant or recessive; however, in syndromic forms, it tends to be autosomal dominant, autosomal recessive, or X-linked.⁴ In families where individuals suffer from congenital anosmia, genetic counseling is often recommended, especially when it occurs as part of a recognized syndrome, to better understand the risk of recurrence and guide future planning.

Management and support

Is there a cure?

At this moment, there is no cure available for congenital anosmia, due to the condition being present from structural or genetic abnormalities, which are irreversible. Therefore, the management usually involves coping strategies and support to minimise the impact the condition has on daily life and safety.³

Safety advice

Many environmental hazards can be difficult to detect in individuals who have congenital anosmia; therefore, they remain at increased risk of danger. Installing working gas leak alarms and smoke detectors in the house is essential. Food should also be handled with extra care because people with anosmia are unable to sense when it is burning or spoiling. Visual inspection, appropriate food storage, and checking expiration dates become crucial procedures to avoid accidents or disease.²

Nutritional and psychological support

Those affected may have a reduced appetite or find eating less enjoyable because the sense of smell has a big impact on taste. To make meals more appealing, diet management should concentrate on improving temperature, colour, and texture. Additionally, psychological assistance could be crucial, particularly for children who might feel different from their friends or get upset by their sensory restrictions.⁶ Self-awareness, coping skills development, and social and emotional difficulties can all be addressed with the aid of counselling or support groups.

Prognosis and quality of life

Despite congenital anosmia not being a life-threatening condition, it can have a noticeable impact on daily life. The loss of smell may influence eating habits due to reduced flavor perception, potentially leading to poor appetite or selective eating. It can also affect personal hygiene, as individuals may be unable to detect body odor or environmental dangers like smoke or gas leaks. 

During childhood and adolescence in particular, social interactions may be affected by feelings of miscommunication or difference. Despite these difficulties, the condition usually remains stable and does not worsen. Management focuses on assisting patients in adapting through safety precautions, dietary plans, and emotional support because there is yet no cure. Most individuals with congenital anosmia can live independent, healthy lives if they have the appropriate awareness and coping mechanisms.² 

Summary

Congenital anosmia is a rare but important condition that is sometimes neglected, especially in early life when symptoms might be modest or misdiagnosed. Even while there might not be any health problems right away, it can have a big impact on safety, nutrition, and quality of life. To guarantee appropriate assistance and management, early detection is crucial, particularly in paediatric and genetic counselling contexts. Better results and earlier diagnosis can result from increasing awareness among families and healthcare professionals. With research into gene therapy and regeneration techniques providing hope for future intervention, developments in genetics and neuroscience may pave the way for possible treatments in the future.