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P L Huygen

Publications and source records attributed to P L Huygen.

At least 19 recordsLinked to original sources
PubMed2003

[From gene to disease; non-syndromic, autosomal dominant, low-frequency sensorineural hearing loss (DFNA6/14)].

DFNA6/-14 is a nonsyndromic, autosomal dominant form of hearing impairment that is characterised by low-frequency sensorineural hearing loss, which in some cases is progressive. It is the only known form of dominantly inherited low-frequency hearing impairment in the Netherlands. It is caused by heterozygous non-inactivating mutations in the WFSI gene, which are also present in the Wolfram or DIDMOAD syndrome.

Audiometry↗
PubMed2001

Fluctuant, progressive hearing loss associated with Menière like vertigo in three patients with the Pendred syndrome.

OBJECTIVE: To evaluate vestibular and long-term audiometric findings in patients with Pendred syndrome. STUDY DESIGN: Retrospective analysis of long-term clinical data. SETTING: University hospital department. PATIENTS: Three patients with Pendred syndrome caused by a mutation in the SLC26A4 gene. METHODS: Perchlorate discharge test, mutation analysis of the SLC26A4 gene, MR imaging of temporal bones, vestibular function test (in two cases) and serial audiometry. A saturation hyperbola with onset age was fitted to the audiometric threshold-on-age data using a nonlinear regression method. The residues remaining after regression were analyzed in a correlation analysis to detect significant ipsilateral or contralateral cofluctuation. RESULTS: All three patients had a mutation in the SLC26A4 gene and bilateral enlarged vestibular aqueduct; two of them had a positive perchlorate discharge test but in one of two siblings this test was negative. Hearing loss was significantly progressive with significant ipsilateral and contralateral cofluctuation in all evaluable cases, combined with episodes of Menière like vertigo in two cases. The episodes of vertigo are as seen in Menière disease. One case had unilateral caloric areflexia and one had bilateral vestibular hyporeflexia, proven to be progressive in a repeat examination. CONCLUSIONS: Patients with Pendred syndrome may exhibit progressive and fluctuant hearing loss with episodes of vertigo.

Adult↗
PubMed2001

The presence of a widened vestibular aqueduct and progressive sensorineural hearing loss in the branchio-oto-renal syndrome. A family study.

OBJECTIVE: A new large family with the BOR syndrome is reported with special reference to the presence of a widened vestibular aqueduct and a progressive sensorineural component in the mixed hearing loss. A review of the BOR literature of 184 patients is given. SETTING: University Hospitals. RESULTS: A BOR family with 17 affected members was studied. Fourteen of those 17 were still alive and 12 of those cooperated in this clinical study. Detailed radiological studies showed in three out of 12 affected family members a widened vestibular aqueduct and progressive sensorineural hearing loss. This raises the question whether there is a true correlation or whether those are coincidental. CONCLUSION: In our family with the Branchio-Oto-Renal syndrome, a widened vestibular aqueduct and progressive hearing loss is found in a few affected family members. Imaging of the temporal bones and long-term audiometric follow-up could help to reveal whether the widened vestibular aqueduct is the cause for the progressive hearing loss.

Adolescent↗
PubMed2001

Autosomal dominant inherited hearing impairment caused by a missense mutation in COL11A2 (DFNA13).

OBJECTIVE: To analyze the phenotype in a 5-generation DFNA13 family with a missense mutation in the COL11A2 gene that causes autosomal dominant, presumably prelingual, nonsyndromic sensorineural hearing impairment. DESIGN: Family study. SETTING: University hospital department. PATIENTS: Twenty mutation carriers from a large American kindred. METHODS: Cross-sectional analysis using pure-tone threshold measurements at 0.25, 0.5, 1, 2, 4, and 8 kHz. The audiometric configuration was evaluated according to an existing consensus protocol. The significance of features relating to audiometric configuration was tested using 1-way analysis of variance. Progression was evaluated with linear regression analyses of threshold-on-age. RESULTS: Most individuals showed midfrequency (U-shaped) characteristics. The mean threshold in generations IV and V was 44 dB at 1, 2, and 4 kHz (midfrequencies); it was 29 dB at the other frequencies (0.25, 0.5, and 8 kHz). There was no significant progression beyond presbyacusis. CONCLUSION: The trait in this family can be characterized as autosomal dominant, nonprogressive, presumably prelingual, midfrequency sensorineural hearing impairment.

Adolescent↗
PubMed2001

Speech recognition scores related to age and degree of hearing impairment in DFNA2/KCNQ4 and DFNA9/COCH.

OBJECTIVE: To analyze the relationship between pure-tone hearing threshold and speech recognition performance in DFNA2/KCNQ4 and DFNA9/COCH, 2 types of high-frequency nonsyndromic hearing impairment. DESIGN: Case series with cross-sectional analysis of phoneme recognition scores related to age and hearing level. SETTING: University hospital. PATIENTS: Forty-five members of 4 separate families, all carrying 1 of 3 different mutations in the KCNQ4 gene at the DFNA2 locus (1p34); 42 members of 7 separate families, all carrying the same Pro51Ser mutation in the COCH gene at the DFNA9 locus (14q12-q13). RESULTS: The deterioration of speech recognition dropped to a 90% score at a higher level of hearing impairment (pure-tone-average at 1, 2, and 4 kHz) in DFNA2-affected patients (65 dB) than in DFNA9-affected patients (46 dB). CONCLUSION: At similar levels of hearing impairment, DFNA2/KCNQ4-affected patients showed better speech recognition performance than DFNA9/COCH-affected patients.

Adult↗
PubMed2001

Diagnosis and treatment of the Pierre Robin sequence: results of a retrospective clinical study and review of the literature.

UNLABELLED: We performed a retrospective study of all children with Pierre Robin sequence (PRS), admitted to our hospital from 1981-1998 in order to evaluate diagnosis, treatment and prognosis. Patients were divided into two categories: isolated PRS (group 1) and PRS plus, i.e. PRS as part of a more complex syndrome (group 2). A total of 74 patients with PRS were found, 29 (39%) males and 45 (61%) females of whom 47 (63.5%) could be categorised as isolated PRS and 27 (36.8%) as PRS plus. The most frequent diagnoses in patients with PRS plus were Stickler syndrome and the velocardiofacial syndrome. Ophthalmological and fluorescent in situ hybridisation of chromosome 22 investigations should therefore be performed in all patients, as soon as the diagnosis of PRS is established. Some form of airway treatment was necessary in the majority of patients (52 of 74), most could be treated conservatively with prone/lateral positioning and close observation. Endotracheal intubation was necessary in one child from group 1 versus five from group 2. Tracheostomy was performed in three children from group 1 and two from group 2. Feeding problems occurred in about 25% of all PRS patients and stunted growth was seen especially in boys with isolated PRS before the age of 10 months. CONCLUSION: In our series, 33% of patients with Pierre Robin sequence plus had Stickler and velocardiofacial syndromes. Conservative airway management was a sufficient treatment for respiratory problems in the majority of patients. Feeding and growth need special attention in patients with Pierre Robin sequence.

Child↗
PubMed2001

A Dutch family with progressive autosomal dominant non-syndromic sensorineural hearing impairment linked to DFNA13.

We present a Dutch family with autosomal dominantly inherited mid-frequency and high-frequency sensorineural hearing impairment. Genetic linkage analysis in this family indicated linkage to DFNA13 with logarithm of the odds ratio (LOD) scores > +4. The majority of the affected persons presented with hearing impairment from the age of 30 years onwards, although hearing impairment was noted at about 10 years of age in two affected persons. Three individuals represent phenocopies. After correction for presbyacusis, hearing impairment was most marked at 1-2 kHz and showed an annual progression of 0.8 dB per year. By the age of 60 years, the configuration of the audiogram was flat, reflecting the combined effects of the inherited progressive hearing loss and presbyacusis. Vestibular function was intact. Recently, mutations in the COL11A2 gene were found in two other families with non-syndromic hearing impairment linked to DFNA13. Further mutation analysis of the COL11A2 gene will show whether this family also contains a COL11A2 mutation.

Audiometry, Pure-Tone↗
PubMed2001

Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a follow-up study of a family.

Cochleovestibular impairment was evaluated, in relation to age, in a longitudinal follow-up study on a Dutch family with a DFNA9 trait caused by a Pro51Ser mutation in the COCH gene on chromosome 14q12-q13. Fourteen cases were genotyped. The onset age of progressive impairment reported by the mutation carriers was between age 35 and 45 years. Pure-tone thresholds deteriorated by about 2-7 dB per year (mean 3.8 dB per year) in a variable, often asymmetrical, fashion. One mutation carrier developed recurrent episodes of vertigo accompanied by nausea and vomiting, resembling Ménière's disease. Two others developed special susceptibility for motion sickness and appeared to have a hyperactive vestibulo-ocular reflex. More advanced stages of vestibular impairment, i.e. vestibular hyporeflexia and complete vestibular areflexia, were eventually found in a number of cases. DFNA9/COCH should be considered as a possible cause in patients developing combined progressive cochlear and vestibular impairment, or suspected hereditary Ménière-like disease, from around middle age.

Adult↗
PubMed2001

Progressive fluctuant hearing loss, enlarged vestibular aqueduct, and cochlear hypoplasia in branchio-oto-renal syndrome.

OBJECTIVE: To study the results of petrosal bone imaging and audiometric long-term follow-up of two patients with branchio-oto-renal (BOR) syndrome and relate them to the clinical features, including caloric responses. STUDY DESIGN: Longitudinal case study. SETTING: Tertiary referral center. PATIENTS: A father and son with the BOR syndrome. MAIN OUTCOME MEASURES: Both patients underwent imaging studies to detect and evaluate inner ear anomalies. Longitudinal audiometric analysis of the hearing threshold data over the previous 23 years was performed. Caloric tests were performed at various ages. RESULTS: The son had a short, wide internal acoustic canal, a hypoplastic cochlea, a plump vestibule, and a wide vestibular aqueduct on both sides; the semicircular canals and endolymphatic sac were of normal size. He showed progressive fluctuant sensorineural hearing loss. Caloric tests disclosed hyporeflexia on the left side. The father had a plump internal acoustic canal and hypoplastic cochlea on both sides. The left vestibule was hypoplastic, and the left vestibular aqueduct was marginally enlarged. He showed severe hearing impairment, without substantial progression or fluctuation, and caloric areflexia on the left side. CONCLUSION: These findings suggest a correlation between progressive fluctuant sensorineural hearing loss with caloric hypofunction and the presence of an enlarged vestibular aqueduct in the BOR syndrome. Additional longitudinal case studies are needed to further evaluate such a correlation.

Adult↗
PubMed2001

The DFNA10 phenotype.

We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-visit audiograms (linear regression analysis, age over 15 years) showed progression of hearing loss at a rate of 0.6 dB/y over all frequencies, with a flat to gently sloping age-corrected threshold of about 50 dB. The results were significant at 0.25, 4, and 8 kHz, but only if corrections for presbycusis were not included. Longitudinal threshold analysis performed in 1 case, covering ages 6 to 32 years, showed progression of hearing loss at a rate of 2 to 3 dB/y over 0.25 to 8 kHz. Nonlinear regression analysis was performed on phoneme discrimination scores with use of sigmoidal dose-response curves with variable slope. On the basis of these data, the hearing loss phenotype in this American DFNA10 family can be described as postlingual, initially progressive, and resulting, without the influence of presbycusis, in largely stable, flat sensorineural deafness.

Adolescent↗
PubMed2000

Changes in the aetiology of hearing impairment in deaf-blind pupils and deaf infant pupils at an institute for the deaf.

An aetiological study was performed on 57 pupils at the deaf-blind department of the Institute for the Deaf at Sint-Michielsgestel, The Netherlands, in the school year 1998-1999 and on 49 deaf-blind pupils at the same department in the school year 1986-1987. The pupils were 5-20 years of age. In addition, the aetiologies were studied in 55 deaf infant pupils in 1998 and compared with those of 68 deaf infant pupils in 1988. Their age was 1-5 years. All the pupils showed hearing impairment with thresholds of >60 dB HL. Among the deaf-blind pupils and deaf infant pupils, there were several cases with rare hereditary syndromes. The prevalence of acquired causes of deafness, especially congenital rubella, had decreased over the years, whereas perinatal causes of deafness had increased. Chromosomal anomalies were found in 15% of the infant pupils in 1998. Over the study period, the percentage of pupils with multiple handicaps increased from 25 to 38%.

Adolescent↗
PubMed2000

Familial progressive vestibulocochlear dysfunction caused by a COCH mutation (DFNA9).

OBJECTIVE: To describe the decline of vestibulocochlear function in a man with vestibulocochlear dysfunction caused by a Pro51Ser mutation within the COCH gene on chromosome 14q12-13 (DFNA9). METHODS: A follow-up of more than 15 years was performed in a single case. Clinical investigations were supplemented by oculomotor, vestibular, and auditory tests. RESULTS: A 50-year-old man had had progressive sensorineural hearing loss and dysequilibrium for 15 years; he had been asymptomatic at the age of 35 years. He suffered from instability in the dark, head movement-dependent oscillopsia, paroxysmal positional vertigo, and vertigo with and without nausea. Hearing impairment started unilaterally, predominantly in the high frequencies. He also reported tinnitus. Disease progressed to severe bilateral high-frequency hearing impairment and vestibular areflexia. Fluctuation of vestibulocochlear function was documented and mentioned by the patient. CONCLUSIONS: Our patient proved to suffer from an autosomal dominant vestibulocochlear disorder caused by a COCH gene mutation. The remarkable medical history has some features in common with Meniere disease; however, there are also different clinical and neurophysiological features. In the family, phenotypic variability is present.

Adult↗
PubMed2000

A Dutch family with progressive sensorineural hearing impairment linked to the DFNA2 region.

We studied a Dutch family with DFNA2-linked progressive sensorineural hearing impairment (SNHI). Recent audiograms were obtained from 18 of the affected persons (age 7-81 years) and were used in a gene-linkage analysis. Linear regression analysis of the audiograms, using binaural mean thresholds, disclosed on average a descending slope of approximately 10 dB/octave at any age and an annual threshold increase at any frequency of about 0.7 dB/year. There may have been substantial congenital impairment at higher frequencies, but longitudinal analysis of hearing impairment in the youngest case, who was followed from age 5 years, suggested that the most significant changes in hearing may have occurred in the first two decades of life. Linkage analysis was carried out with special attention to the DFNA2 region because hearing trends were very similar to families previously linked to DFNA2. Linkage to DFNA2 was established with maximum lod scores of 4.7 and 3.2 for the flanking markers of the DFNA2 region (D1S432;MYCL1).

Adolescent↗
PubMed2000

Hearing loss in the nonocular Stickler syndrome caused by a COL11A2 mutation.

OBJECTIVE: Evaluation of hearing impairment as a feature of the nonocular Stickler syndrome (type II) linked to COL11A2. STUDY DESIGN: Family study. METHODS: General, orthopaedic, ophthalmologic, and otorhinolaryngologic examinations were performed on 15 affected persons in a Dutch family. Audiograms were obtained and/or retrieved from elsewhere. Cross-sectional and longitudinal analyses were conducted on the hearing threshold (sensorineural component) in relation to the patient's age to evaluate whether hearing impairment was progressive. RESULTS: Mixed hearing loss, i.e., including a substantial air-bone gap of up to 20 to 60 dB, was present in six cases, concomitantly with a submucous or overt cleft palate in five of them. The audiograms in 14 evaluable cases showed the following types of threshold: U-shaped (n = 3), flat (n = 2), flat or gently (downward) sloping (n = 3), gently sloping (n = 3), or steeply sloping (n = 3). Cross-sectional analysis did not reveal any significant effect of age on sensorineural hearing impairment. CONCLUSION: In contrast to the classic Stickler syndrome (type I) with high myopia, this nonocular type shows a high prevalence of sensorineural hearing impairment. The mean sensorineural hearing threshold in our patients was about 40 dB HL (95% CI, 15-65 dB) and was liable to increase (presumably by presbycusis) by several tens of decibels at the highest frequencies. Given the tendency for otitis media to develop in many of these patients, appropriate otologic care is of major importance.

Adult↗
PubMed1999

Causes of hearing impairment in deaf pupils with a mental handicap.

An aetiological study was performed on 122 deaf pupils (57 aged < 20 years, 65 aged > 20 years) at the Institute for the Deaf in Sint-Michielsgestel, The Netherlands. Besides hearing impairment with thresholds of > 60 dB HL, all the participants had a mental handicap with a non-verbal IQ of 40-80. Sixteen per cent of them were of non-Dutch origin. The cause of hearing impairment was acquired in 48%, inherited in 17%, chromosomal in 4% and unknown in 30%. In comparison with other studies on the aetiology of childhood deafness, acquired causes predominated over inherited causes, which may be typical of deafness combined with a mental handicap. We found a significant predominance of non-Dutch pupils among the rubella aetiology cases and male predominance among the hearing impaired pupils in general.

Adolescent↗
PubMed1999

[Whipple's disease].

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Anti-Bacterial Agents↗
PubMed1999

Hearing impairment and neurological dysfunction associated with a mutation in the mitochondrial tRNASer(UCN) gene.

We studied a large Dutch family with maternally inherited, progressive, sensorineural hearing loss in 27 patients. Only in a single family member was the hearing loss accompanied by neurological symptoms including ataxia and dysarthria. DNA analysis of the mitochondrial genome revealed the insertion of a C at nucleotide position 7472 in the tRNASer(UCN) gene (7472insC mutation). We determined the percentage of mutant DNA (heteroplasmy) in blood from all family members, and found no correlation between hearing loss and leucocyte heteroplasmy. The 7472insC mutation was previously identified in a smaller family from Sicily with sensorineural hearing loss in 9 family members, six of them also presenting neurologically with ataxia and myoclonus. The presence of the 7472insC mutation in two different pedigrees strongly supports its pathogenicity. However, the interfamilial difference in penetrance of the neurologic abnormalities is most likely to be strongly influenced by secondary factors different from the 7472insC mutation, as heteroplasmy or age of the patients were similar in both families. This mutation should therefore be analysed in families with maternally inherited hearing loss, irrespective of whether the hearing loss is non-syndromic or accompanied by neurologic abnormalities.

Aminoglycosides↗