Congenital anosmia

Congenital anosmia may occur as an isolated abnormality or be associated with specific genetic disorders (such as Kallmann syndrome and congenital insensitivity to pain).

Most cases of isolated congenital anosmia (not associated with additional symptoms) occur sporadically in people with no family history of the condition. In these people, the exact underlying cause of the condition is unknown. Scientists suspect that the condition is due to abnormal development of the olfactory system (the sensory system used for sense of smell) prior to birth. This may include abnormalities of the nasal cavity; disruptions in the pathway that carries information from the nose to the brain; or malformations of the portion of the brain that processes sense of smell.

When isolated congenital anosmia affects more than one family member, it may have a genetic component. One study found that some people affected by isolated congenital anosmia have changes (mutations) in the PROKR2 gene or PROK2 gene. These genes have previously been reported in people with Kallmann syndrome (an inherited condition associated with congenital anosmia and other symptoms). Another study found that two brothers with anosmia had a mutation in the CNGA2 gene. However, in most familial cases of isolated congenital anosmia, the cause remains unknown.

Isolated congenital anosmia (not associated with other symptoms) is a diagnosis of exclusion. This means that the diagnosis is made by ruling out all known conditions that may cause an absent sense of smell. When an affected person has no recollection of ever being able to smell, the following tests may be ordered to support a diagnosis of congenital anosmia:

• A thorough physical examination and medical history to look for other conditions that may interfere with sense of smell
• Smell tests, particularly those that determine the smallest amount of odor that someone can detect
• Brain Imaging (such as CT scan and MRI scan) to look for malformations in the portion of the brain that processes smell
• Nasal endoscopy to look for abnormalities of the nasal cavity which may interfere with sense of smell
• Olfactory nerve testing to evaluate disruptions in the pathway that carries information from the nose to the brain

Most cases of isolated congenital anosmia (not associated with additional symptoms) occur sporadically in people with no family history of the condition. Rarely, more than one family member may be affected. In these families, inheritance appears to be autosomal dominant with reduced penetrance. Autosomal dominant inheritance means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. Reduced penetrance means that not all people who have or inherit the mutation will be affected. When a person with a mutation that causes an autosomal dominant condition has children (whether they are affected or not), each child has a 50% (1 in 2) chance to inherit that mutation. For conditions with reduced penetrance, it is not possible to predict whether a child who inherits the mutation will be affected. In most familial cases of isolated congenital anosmia, the genetic cause is unknown.

Congenital anosmia can also by associated with hereditary genetic disorders such as Kallmann syndrome and congenital insensitivity to pain. In these cases, it is inherited in the same manner as the associated condition. For example, Kallmann syndrome can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner depending on the underlying genetic cause (it can be caused by mutations in several different genes). Congenital insensitivity to pain has an autosomal recessive pattern of inheritance.

Studies suggest that approximately 1 in 10,000 people are affected by congenital anosmia. This includes people affected by isolated congenital anosmia (no additional symptoms) and those with congenital anosmia caused by a specific genetic disorder (such as Kallmann syndrome or congenital insensitivity to pain).

Unfortunately, there is currently no known cure or treatment for congenital anosmia.