Mondini dysplasia

Mondini dysplasia is a congenital malformation (present at birth). It may occur either unilaterally (in one ear) or bilaterally (in both ears). Most affected individuals have profound sensorineural hearing loss, but some individuals do have residual hearing.^[1] There have also been reports of affected individuals having normal hearing.^[6] Mondini dysplasia can also predispose to recurrent meningitis because the defect can act as a "port of entry" to the fluid that surrounds the brain and spinal cord (cerebrospinal fluid, or CSF). Sometimes, individuals are not diagnosed before several episodes of recurrent meningitis occur.^[1] The condition may occur with other abnormalities of the ear or other organs, or it may be isolated. The severity of the physical abnormality does not appear to correlate with the severity of the signs and symptoms in affected individuals.^[6]

The underlying cause of Mondini dysplasia (MD) in most individuals appears to remain unclear. Some have suggested that retinoids (vitamin A) or other factors a fetus may be exposed to early in pregnancy have contributed to some cases of isolated MD (occurring with no other abnormalities). The potential role of these factors has created increased difficulty in determining the real cause of isolated MD.^[4]

Mutations in the SLC26A4 gene cause both Pendred syndrome and DFNB4 (non-syndromic hearing loss with inner ear abnormalities), which are both associated with MD.^[4][1] Though mutations in the SLC26A4 gene have also been found in individuals with enlarged vestibular aqueduct (EVA) with and without MD, studies have shown there does not appear to be a relationship between isolated MD and the SLC26A4 gene. Thus hearing impairment in individuals with isolated MD may be caused by factors other than mutations in the SLC26A4 gene.^[4] More recently, a type of mutation called a microdeletion (a tiny loss of genetic material on a chromosome that may span several genes) involving the POU3F4 gene on the X chromosome was detected in some individuals with familial MD.^[5]

In cases where Mondini dysplasia is associated with a specific syndrome, the cause of the syndrome in the affected individual is assumed to be related to the occurrence of MD in those cases. Syndromes that have been associated with MD include Klippel Feil syndrome, Pendred syndrome, DiGeorge syndrome, and some chromosomal trisomies.^[1]

Mondini dysplasia usually occurs sporadically as an isolated abnormality (occurring in only one individual in a family with no other abnormalities) but it can be associated with a variety of syndromes including Klippel Feil syndrome, Pendred syndrome, DiGeorge syndrome, Wildervanck syndrome, Fountain syndrome, Johanson-Blizzard syndrome, and some chromosomal trisomies.^[1][7] These syndromes can be inherited in a variety of ways, but Mondini dysplasia may not occur in each affected individual. It has also has been reported in families with congenital sensorineural hearing loss, both with autosomal dominant and presumed autosomal recessive inheritance.^[8] One study described familial nonsyndromic Mondini dysplasia in a mother, son and daughter with presumed autosomal dominant inheritance;^[7] another study described familial nonsyndromic Mondini dysplasia in a family in which transmission was most consistent with autosomal recessive inheritance.^[7] It has also been suggested that Mondini dysplasia may be associated with substances that may harm a developing fetus when a pregnant woman is exposed (teratogens) such as thalidomide or rubella.^[7] Being that Mondini dysplasia has been associated with a variety of conditions, inheritance patterns, and both genetic and non-genetic causes, it appears to be inherited in some cases, with the inheritance pattern being dependent upon the underlying cause of the condition in each individual or family.

Genetic testing may be available for Mondini dysplasia if it is associated with a specific syndrome for which genetic testing is available, or if a mutation has previously been identified in an affected individual in the family. Unfortunately, for many cases of isolated Mondini dysplasia, there is no clinical genetic testing available.

GeneTests lists the names of laboratories that are performing genetic testing for many conditions that may be associated with Mondini dysplasia. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

Surgery to repair the defect present with Mondini dysplasia is typically necessary to prevent recurrent meningitis.^[3][5] Prophylactic antimicrobial therapy (such as antibiotics) to prevent infection and conjugate pneumococcal vaccination are helpful in reducing the formation of bacteria in affected individuals.^[3] If an individual has residual hearing, hearing amplification aids may be useful.^[6] The use of cochlear implants to treat patients with inner ear malformations such as Mondini dysplasia has been increasingly successful. Various results of cochlear implantation in individuals with Mondini dysplasia have been reported in the literature.^[6]