Paediatric Hearing Loss

Permanent childhood hearing impairment (PCHI) is defined as permanent bilateral hearing impairment ≥40 dB HL (hearing level) averaged over 0.5, 1, 2, and 4 kHz in the better-hearing ear. Onset may be prenatal, perinatal, or postnatal, and aetiology may be congenital or acquired

One infant per thousand is born with permanent deafness or significant hearing impairment. A further one infant per thousand develops permanent deafness during childhood.

Syndrome	Implicated genes	Clinical features
Pendred's syndrome Hearing loss Balance Goitre	SLC26A4 pendrin gene—Chr 7 SLC26A4 gene mutations that encode the dysfunctional protein pendrin. Pendrin, a chloride/iodide/bicarbonate exchanger Thyroid Dysfunction: Pendrin is expressed on the apical membrane of thyroid cells, where it plays a key role in mediating iodide efflux into the follicular lumen, a critical step for iodine organification and thyroid hormone synthesis. Lack of functional pendrin leads to a partial defect in this process, frequently causing a goiter (enlarged thyroid) and sometimes hypothyroidism, though thyroid levels can be normal. Inner Ear Dysfunction: In the inner ear, pendrin regulates the ion composition of the endolymph. Dysfunction leads to an abnormal buildup of fluid in the endolymphatic sac (enlarged vestibular aqueduct) and improper development of the cochlea (often leading to a Mondini malformation, which is a cochlea with 1.5 turns instead of 2.5). This leads to sensorineural hearing loss.	Most common syndromal deafness, 7–8% of congenital hearing loss: Severe SNHL Euthyroid goitre in puberty. Widening of vestibular aqueduct (Mondini dysplasia) can cause vestibular disturbance, also in branchio-oto-renal syndrome (BOR) and nonsyndromic deafness.
Usher’s syndrome (USH)	15 loci and 12 genes— MY07A/CDH23	50% of deaf-blind children in the United States. Three major types are distinguished by severity of deafness, vestibular dysfunction, and age of onset. Type 1 patients have: Congenital severe-to-profound SNHL Vestibular dysfunction Retinitis pigmentosa
Jervell and Lange-Nielsen syndrome	KVLQT1 gene Chr 11 KCNE1 gene–Chr 21	Elongation of QT interval on ECG causing fainting and sudden death. Highly associated with consanguinity.

Syndrome

Implicated genes

Clinical features

Pendred's syndrome

Hearing loss
Balance
Goitre

SLC26A4 pendrin gene—Chr 7

SLC26A4 gene mutations that encode the dysfunctional protein pendrin. Pendrin, a chloride/iodide/bicarbonate exchanger

Thyroid Dysfunction: Pendrin is expressed on the apical membrane of thyroid cells, where it plays a key role in mediating iodide efflux into the follicular lumen, a critical step for iodine organification and thyroid hormone synthesis. Lack of functional pendrin leads to a partial defect in this process, frequently causing a goiter (enlarged thyroid) and sometimes hypothyroidism, though thyroid levels can be normal.

Inner Ear Dysfunction: In the inner ear, pendrin regulates the ion composition of the endolymph. Dysfunction leads to an abnormal buildup of fluid in the endolymphatic sac (enlarged vestibular aqueduct) and improper development of the cochlea (often leading to a Mondini malformation, which is a cochlea with 1.5 turns instead of 2.5). This leads to sensorineural hearing loss.

Most common syndromal deafness, 7–8% of congenital hearing loss:

Severe SNHL
Euthyroid goitre in puberty.
Widening of vestibular aqueduct (Mondini dysplasia) can cause vestibular disturbance, also in branchio-oto-renal syndrome (BOR) and nonsyndromic deafness.

Usher’s syndrome (USH)

15 loci and 12 genes— MY07A/CDH23

50% of deaf-blind children in the United States. Three major types are distinguished by severity of deafness, vestibular dysfunction, and age of onset. Type 1 patients have:

Congenital severe-to-profound SNHL
Vestibular dysfunction
Retinitis pigmentosa

Jervell and Lange-Nielsen syndrome

KVLQT1 gene

Chr 11
KCNE1 gene–Chr 21

Elongation of QT interval on ECG causing fainting and sudden death. Highly associated with consanguinity.