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Biomedical subjects

K M Grundfast

Publications and source records attributed to K M Grundfast.

At least 37 records · Page 2Linked to original sources
PubMed1994

A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2.

X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available, polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at theta = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3' to exon 50 of the dystrophin gene) and at DXS1068 (5' to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5'DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described.

Audiometry↗
PubMed1994

Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes.

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.

Chromosome Mapping↗
PubMed1992

Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium.

Previous studies have localized the gene for Waardenburg syndrome (WS) type I to the distal portion of chromosome 2q, near the ALPP locus. We pooled linkage data obtained from 41 WS type I and 3 WS type II families which were typed for six polymorphic loci on chromosome 2q in order to refine the location of the WS locus (WS1) and evaluate the extent of genetic heterogeneity. In the course of this work, we developed diagnostic criteria for genetic and phenotypic studies. Our findings, based on two-locus and multilocus analysis using a linkage map established from reference pedigrees, suggest that there are two or more mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q, between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each marker, respectively. The results also indicate that WS1 is responsible for the illness in approximately 45% of all families in this sample. However, the odds favoring this position over a location between ALPP and SAG are only 2:1 when alternate assumptions about the proportion of linked families are considered. We conclude that a more saturated map of this region of chromosome 2q, including highly polymorphic markers, will be needed to accurately distinguish linked families and, ultimately, isolate the mutant gene.

Alkaline Phosphatase↗
PubMed1992

Finding the gene(s) for Waardenburg syndrome(s).

Waardenburg syndrome is a recognizable disorder characterized by autosomal dominant inheritance of pigmentary abnormalities of the eyes, hair, and skin sometimes associated with congenital hearing impairment. At least two different types of Waardenburg syndrome have been described. The different types of Waardenburg syndrome are differentiated as follows: type I, with dystopia canthorum; type II, without dystopia canthorum; and type III, without dystopia, with unilateral eyelid ptosis and skeletal abnormalities. Results of pooled linkage analysis done by a consortium of investigators suggests that Waardenburg syndrome type I is genetically heterogeneous, meaning that there is probably more than one genotype that can be associated with the findings typical of the syndrome. A mutated gene that can cause Waardenburg syndrome type I has been discovered. Either a single base pair substitution or an 18 base pair deletion in exon 2 has been found in affected individuals but is not found in unaffected members. Most likely, the mutated gene causes a perturbation in DNA binding of a paired domain, in turn having an effect on the regulation of other genes so the development and spatial orientation of cells and structures derived from the neural crest are affected. Forty years after Waardenburg syndrome was first described, a mutant gene has been found that is known to cause the syndrome. The process of discovery that has transpired in the time from syndrome description to gene identification has been one of steady progress and interdisciplinary cooperation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Complete evaluation of the child identified as a poor listener.

With increasing awareness among educators of the importance of early identification of hearing impairment, growing numbers of children are being referred for evaluation when a teacher or day care supervisor perceives that a child is having difficulty listening. Some children who manifest difficulty listening in a pre-school play group or the classroom may have conductive or sensorineural hearing loss, while others have normal hearing with an underlying and yet-to-be-detected behavioral or psychoeducational disorder. This report presents suggestions for evaluation of the child referred for difficulty listening. The otologist should consider that a child may have an attention deficit disorder when results of initial audiologic assessment indicate there is no hearing loss or when the degree of hearing loss appears to be small in relation to the degree of inattentiveness that has been observed. The features of Attention-deficit Hyperactivity Disorder (ADHD) and Specific Developmental Disorder (SDD) are described, and illustrative case studies are presented. Clues to diagnosis are provided and a distinction between overlapping disorders is made.

Attention↗
PubMed1991

Laryngeal pathology in hearing-impaired children.

Eighty-five children enrolled in a total communication elementary school for the severe-to-profoundly hearing-impaired were evaluated prospectively to assess the incidence of laryngeal abnormalities. Direct flexible laryngoscopy and indirect mirror laryngoscopy revealed vocal cord nodules in 3 children, omega-shape infantile epiglottis in 3 children, and normal larynges in the remaining 79 children. These findings suggest that severe-to-profoundly hearing-impaired children develop detectable laryngeal pathology at approximately the same frequency as previously reported by others for normal hearing children.

Adolescent↗
PubMed1991

Adenotonsillectomy in children with sickle cell disease.

The pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia. With proper patient selection and appropriate perioperative management, adenotonsillectomy can be accomplished safely in children with sickle cell disease. We review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy. Indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children. No complications resulted from any of these procedures, and the mean length of postoperative hospitalization was 2.4 days. The principal feature of preoperative management was the transfusion of red blood cells to suppress the patient's endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30%. Though a prospective, multi-institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease, balancing the risks of transfusion-related complications against anesthesia-related complications, our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease.

Adenoidectomy↗
PubMed1991

Management of otolaryngic patients susceptible to malignant hyperthermia without dantrolene.

Malignant hyperthermia (MH) is an adverse reaction most frequently associated with the administration of halogenated inhalational anesthetic agents and the depolarizing muscle relaxant succinylcholine. Characteristic findings are a hypermetabolic state accompanied by extreme hyperpyrexia, acidosis, rhabdomyolysis, and generalized muscle rigidity, often involving the masseter muscles. Dantrolene sodium, which was approved in 1979 by the FDA for use in the prevention of MH in high-risk patients, has neurologic and gastrointestinal side effects. At the Children's National Medical Center (CNMC), 24 children identified as being at risk for the development of a MH reaction were anesthetized for otolaryngic procedures by using "non-triggering" anesthetics and without use of dantrolene sodium. These patients represent 56% of all patients at risk for MH or masseter muscle rigidity (MMR) reactions during an 8-year period at the CNMC. There were no complications. Concomitant muscle biopsies were performed, and caffeine/halothane contracture studies were completed in 18 of these patients, demonstrating 11 susceptible or equivocal responses. The data suggest that children undergoing common otolaryngic procedures who are at risk for development of MH may be safely anesthetized without the use of prophylactic dantrolene sodium.

Anesthesia↗
PubMed1990

Diverse etiologies of facial paralysis in children.

Facial paralysis (FP) in children is most often idiopathic, however, many diverse and identifiable etiologies exist. Twenty-five cases of children admitted consecutively to the Children's National Medical Center over 8.5 years for the evaluation of FP were reviewed retrospectively. In 21 (84%) of the patients the FP was discovered to be secondary to a specific etiology or associated with a recognizable syndrome. In 7 cases, the FP was an initial manifestation of a serious underlying disorder. Causes of the FP in this series include: otitis media, mastoiditis, temporal lobe abscess, osteopetrosis, both blunt and penetrating trauma, iatrogenic surgical injury, facial burns, cerebellar astrocytoma, leukemia rhabdomyosarcoma, intracerebral arteriovenous malformation, Goldenhar syndrome, and Melkersson-Rosenthal syndrome. Four (16%) patients were diagnosed as having Bell's palsy. Methods of management, including the use of electrodiagnostic testing are described.

Adolescent↗
PubMed1990

Airway compromise from nasal obstruction in neonates and infants.

Nasal obstruction in neonates can cause significant airway compromise and even be life-threatening. In general, otolaryngologists are familiar with management of the neonate born with choanal atresia but there have been few reports and there are no guidelines for management of the neonate or young infant who presents with nasal obstruction and airway compromise but who does not have choanal atresia (NOWCA). This study demonstrates the difficulty in diagnosis, variability in severity of airway compromise, and delineates the problematic aspects of management.

Adenoids↗
PubMed1990

Prospective study of subglottic stenosis in intubated neonates.

Although numerous retrospective studies have attempted to investigate the incidence, etiology, and pathogenesis of subglottic stenosis, there have been few prospective studies. The retrospective studies focused initially on diagnosed cases, then drew inferences regarding incidence and causality based upon data obtained from review of patient records. In contrast, this prospective study accrued data on all neonates intubated for 48 hours or longer during the 1-year intake period. There were 195 neonates entered in the study; then 36 were excluded, leaving 159 for data analysis. Parameters assessed included age at intubation (mean, 5.7 days), duration of intubation (mean, 12.3 days), and number of times reintubated (mean, 0.79). Results of this prospective study are compared to results from previous retrospective studies.

Causality↗