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Biomedical subjects

W Reardon

Publications and source records attributed to W Reardon.

At least 127 records · Page 7Linked to original sources
PubMed1992

Molecular analysis for the myotonic dystrophy mutation in neuromuscular disorders.

A variable expansion of an unstable CTG repeat has been identified as the causal mutation for myotonic dystrophy. Standard molecular genetic techniques can now supplement traditional assessment protocols in a variety of clinical neurological situations where diagnostic uncertainty prevailed. Southern analysis using DNA probes which identify the expanded sequence, supplemented by direct PCR analysis for repeat number, provides a specific sensitive diagnostic test for myotonic dystrophy.

Adult↗
PubMed1992

Lethal congenital erythroderma: a newly recognised genetic disorder.

We report 4 patients and their extended families comprising 17 cases, all of whom had congenital exfoliative erythroderma resistant to treatment, associated with failure to thrive and hypoalbuminaemia. All died in the first year of life. This condition appears to be inherited in an autosomal recessive manner and the underlying defect remains unknown.

Consanguinity↗
PubMed1992

Anal abnormalities in childhood myotonic dystrophy--a possible source of confusion in child sexual abuse.

Myopathic involvement of the perianal musculature is one of the less well recognised features of myotonic dystrophy in children and may present with physical signs suggestive of sexual abuse. Details of six children with myotonic dystrophy are presented to emphasise the importance of considering an underlying myopathic condition in the differential diagnosis of anal laxity.

Adolescent↗
PubMed1992

Minimal expression of myotonic dystrophy: a clinical and molecular analysis.

A clinical and molecular study is reported of 83 patients considered to be minimally affected with myotonic dystrophy (DM). These had been identified in three ways: 60 subjects were identified on clinical grounds and were divided into those with and those without neuromuscular involvement (groups I and II); nine subjects were at high risk of carrying the DM gene but had a normal phenotype (group III); and 14 were parents of definitely affected patients where neither parent showed clinical abnormalities (group IV). PCR analysis of the CTG repeat in the DM gene showed a range of 70 to 230 repeats for the younger at risk patients in group III, while the asymptomatic gene carriers in group IV had 53 to 60 repeats. The sensitivity of diagnosis by EMG was found to be 39%. For ophthalmic signs this was 97.5%. This suggests that assignment on the basis of minimal clinical features carries a significant error. Molecular analysis, in conjunction with established clinical investigations, should prove valuable in the identification and exclusion of minimal myotonic dystrophy.

Adult↗
PubMed1992

Clinical and genetic heterogeneity in X-linked deafness.

The use of molecular techniques in respect of the rare X-linked non-syndromic form of genetic deafness demonstrates that this is a genetically heterogeneous disorder, with evidence for at least two separate gene loci on the X chromosome. Audiological heterogeneity in this condition is emphasized by the observation of both mixed deafness and sensorineural deafness in pedigrees showing evidence for linkage to Xq13-q21. The importance and shortcomings of the audiogram in assessing females who are known gene carriers is discussed.

Adolescent↗
PubMed1992

Advances in myotonic dystrophy: a clinical and genetic perspective.

The recent identification of the gene responsible for myotonic dystrophy and the recognition of an expanding unstable repeat sequence as the specific molecular defect, have resulted in rapid changes in clinical practice as well as in our understanding of the disorder. Against such a framework, this review traces the evolution of clinical and genetic knowledge of the disorder and emphasizes the continuing central role of thorough clinical investigation of those at risk for carrying the gene as an essential element of predictive testing for myotonic dystrophy.

Chromosomes, Human, Pair 19↗
PubMed1992

Anticipation in myotonic dystrophy: new light on an old problem.

The concept of anticipation, the occurrence of a genetic disorder at progressively earlier ages in successive generations, has been debated from the early years of this century, with myotonic dystrophy as the most striking example. Throughout most of this period there has been controversy as to whether the phenomenon resulted from observational and ascertainment biases or reflected a more fundamental mechanism. The recent discovery of inherited unstable DNA sequences, first in fragile-X mental retardation and now in myotonic dystrophy, not only confirms that anticipation indeed has a true biological basis but provides a specific molecular mechanism for it; this discovery can explain many of the puzzling anomalies in the inheritance of myotonic dystrophy and may prove relevant to comparable problems in other genetic disorders.

Chromosome Fragility↗
PubMed1992

Microdeletions in patients with gusher-associated, X-linked mixed deafness (DFN3).

Employing various probes from the proximal part of the Xq21 region, which is known to harbor the DFN3 gene, we have investigated 13 unrelated male probands with X-linked deafness, to detect possible deletions. For two of these patients, microdeletions could be detected by using probe pHU16 (DXS26). One of these deletions also encompasses locus DXS169, indicating that it extends farther toward the centromere. The presence of normal hybridization patterns in the DNA of 25 unrelated control males suggests that these deletions are the primary cause of progressive mixed deafness in these patients. If so, their molecular characterization may pave the way for the identification and isolation of the corresponding gene.

Chromosome Deletion↗
PubMed1991

X-linked deafness, stapes gushers and a distinctive defect of the inner ear.

The association of X-linked mixed deafness with stapes gusher has been recognized for 20 years, and imaging studies by polytomography have shown dilatation of the lateral end of the internal auditory meatus (IAM) in some cases. We have made genetic linkage studies in 7 pedigrees in whom deafness was inherited in an X-linked manner. All patients had a full range of audiometric and vestibular function tests. Thin section high resolution CT in two planes was used to assess the state of the middle and inner ears. We found a distinctive inner ear deformity in some of the deaf males characterised not only by a wide bulbous IAM but more importantly, by deficient or absent bone between the lateral end of the IAM and the basal turn of the cochlea. We believe that this results in a communication between the subarachnoid space in the IAM and the perilymph in the cochlea, leading to perilymphatic hydrops and a "gusher" if the stapes is disturbed. Moreover, some of the obligate female carriers seem to have a milder form of the same anomaly associated with slight hearing loss. Genetic studies on some of the deaf males with apparently normal inner ear anatomy suggest a different locus on the X chromosome and hence a different pathogenesis for the deafness.

Audiometry↗
PubMed1991

A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.

A locus for X-linked nonsyndromic deafness has previously been allocated to the Xq13-q21 region based on linkage studies in two separate pedigrees. This has been substantiated by the observation of deafness as a clinical feature of male patients with cytogenetically detectable deletions across this region. The question of a second locus for deafness in this chromosomal region has been raised by the audiologically distinct nature of the deafness in some of the deleted patients compared to that observed in those patients upon whom the linkage data are based. We have performed detailed clinical evaluation and linkage studies on seven pedigrees with nonsyndromic X-linked deafness and conclude that there is evidence for at least two loci for this form of deafness, including one in the Xq13-q21 region. We have observed different radiological features among the pedigrees which map to Xq13-q21, suggesting that even among these pedigrees the deafness is due to different pathological processes. Given these findings, we suggest that the classification of nonsyndromic X-linked deafness based solely on audiological criteria may need to be reviewed.

Chromosome Mapping↗
PubMed1991

Atypical facio-scapulo-humeral muscular dystrophy--a counselling dilemma.

In an isolated male patient, differentiation between Facio-Scapulo-Humeral Muscular Dystrophy (FSH) and Becker Muscular Dystrophy (BMD) may be difficult. To emphasise this point, we report a patient, whose features are atypical of FSH. Details of his daughter who now manifests similar presenting features, are provided. The pitfalls posed for the genetic counsellor by FSH presenting in an atypical manner which clinically overlaps with genetically distinct conditions are discussed in the light of this pedigree.

Adult↗
PubMed1991

Sibs with mental retardation, supraorbital sclerosis, and metaphyseal dysplasia: frontometaphyseal dysplasia, craniometaphyseal dysplasia, or a new syndrome?

A brother and sister are presented with unusual facies, bilateral mixed hearing loss, mental retardation, and widespread radiological abnormalities. The clinical and radiological evidence for and against the two most likely diagnoses of frontometaphyseal dysplasia and craniometaphyseal dysplasia is considered.

Abnormalities, Multiple↗
PubMed1990

Frontonasal dysplasia or craniofrontonasal dysplasia and the Poland anomaly?

We describe a 10-year-old girl with features of a frontonasal dysplasia and a right-sided Poland anomaly. As there has been one previous case report of pectoral muscle hypoplasia in association with craniofrontonasal dysplasia, the relationship between these two conditions is discussed.

Abnormalities, Multiple↗
PubMed1990

Partial lipodystrophy syndromes--a further male case.

Details are presented of a boy with partial lipodystrophy. Only one male case has previously been described with this condition. The spectrum of partial lipodystrophy syndromes and the inheritance thereof are discussed in relation to our case.

Genetic Counseling↗
PubMed1990

Two brothers with heart defects and limb shortening: case reports and review.

Two male Arab sibs are reported with congenital heart disease and skeletal malformations. Other published case reports sharing some features in common with these brothers are considered. However, clinical and radiological features in these boys are distinct enough to represent a new cardioskeletal syndrome.

Abnormalities, Multiple↗