Characteristics of Hearing Loss in HDR (Hypoparathyroidism, Sensorineural Deafness, Renal Dysplasia) Syndrome

Abstract

Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR syndrome. The purpose of the current study was to describe in detail the auditory phenotype in human HDR patients and compare these to audiometrical and histological data previously described in a mouse model of this disease. Pure tone audiometry, speech audiometry, speech in noise, auditory brainstem responses and transiently evoked otoacoustic emissions were measured in 2 patients affected by HDR syndrome. Both patients were affected by a moderate-to-severe sensorineural hearing loss. Speech reception thresholds were shifted and speech recognition in noise was disturbed. No otoacoustic emissions could be generated in either patient. Auditory brainstem response interpeak intervals were normal. The human and murine audiological phenotypes seem to correspond well. Hearing loss in HDR syndrome is moderate to severe, seems to be slightly worse at the higher end of the frequency spectrum and may be progressive with age. The absence of otoacoustic emissions and the loss of frequency selectivity suggest an important role for outer hair cells in causing the hearing loss.

Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2

“…However, it is important to note that the altered renal morphogenesis is observed in Gata3 -/-mice but not in Gata3 +/-mice, while HDR patients, who are also heterozygous for the GATA3 mutation, have abnormal kidneys (7). In contrast, deafness is found to occur in Gata3 +/-mice and is similar to that in HDR patients (12)(13)(14). The deafness in Gata3 +/-mice is due to abnormalities of the inner ear, which include early degeneration of the inner ear hair cells, and part of the underlying mechanism involves abnormalities of the insulin-like growth factor signaling pathway that includes the serine/threonine kinase Akt/PKB (10,14).…”

Novel DNA mutation in the GATA3 gene in an Emirati boy with HDR syndrome and hypomagnesemia

“…The hearing loss was typical of HDR syndrome, being bilateral, sensorineural, moderate (60 dB), and over all frequencies but more pronounced at the high frequencies. Hearing loss in HDR syndrome is usually moderate to severe, and slightly worse at the higher end of the frequency spectrum; it is also progressive with age [4,5,14,17]. Renal hypoplasia as found in our patient is one of the many developmental renal anomalies described in HDR syndrome [2,3].…”

Audiometric Characteristics of a Dutch Family with a New Mutation in <b><i>GATA3</i></b> Causing HDR Syndrome

“…Figure 5 shows the ΔS/N for individuals I:1, II:2 and II:4. The average results for Usher2A patients, presbyacusis patients and 2 HDR patients previously published on are also displayed for comparison [De Leenheer et al, 2002;Leijendeckers et al, 2009;van Looij et al, 2006]. A high bar indicates a poor speech reception threshold in conditions of noise.…”

“…The S/N ratio was subtracted from the S/N ratio of normal-hearing individuals (ΔS/N). The outcomes of speech perception in noise were compared with those of patients with presbyacusis [Bosman and Smoorenburg, 1995], to Usher2A patients [Leijendeckers et al, 2009] and to 2 HDR patients previously published on [van Looij et al, 2006].…”

“…The higher frequencies were more often affected than the lower frequencies. Table 1 presents a review of the audiological data published on HDR syndrome [Bilous et al, 1992;Fujimoto et al, 1999;Hasegawa et al, 1997;Hernández et al, 2007;Lichtner et al, 2000;Moldovan et al, 2011;Muroya et al, 2001;Nakamura et al, 2011;van Looij et al, 2006;Zahirieh et al, 2005]. In addition, van Looij et al [2006] tested speech perception in conditions of noise in 2 HDR patients and reported poor results.…”