Search PubMed⌕ Search

Biomedical subjects

R M Pauli

Publications and source records attributed to R M Pauli.

At least 37 records · Page 2Linked to original sources
PubMed1997

Autosomal dominant hypohidrotic ectodermal dysplasia in a large family.

We have studied an autosomal dominant hypohidrotic ectodermal dysplasia in 38 individuals over six generations in one family. Thirty-two affected individuals in four generations are still living. Questionnaire responses were received from 21 of the affected relatives and some of the individuals were examined by one of the authors. Smooth, dry, thin skin is seen in most affected individuals. Nearly all have fine, slow-growing scalp and body hair and all have sparse eyebrows and short eyelashes. Nearly all show a decrease in sweating, with some only sweating under the arms and/or on the palms and soles. All affected individuals lacked some deciduous teeth and some permanent teeth. Some teeth are abnormally shaped. Nail abnormalities are more variable and may occur more frequently with increasing age. No other abnormalities are seen in affected individuals in this family. We reviewed 40 autosomal dominant ectodermal dysplasia syndromes. This family bears some resemblance to a family described by Jorgensen et al. [1987]; however, it appears to represent a disorder that has not been described previously.

Abnormalities, Multiple↗
PubMed1997

Validation of radiographic criteria for the diagnosis of Down syndrome in stillborn infants.

We assessed the utility of radiographic findings as aids to the diagnosis of Down syndrome (DS) in stillborn infants. The iliac index may help to confirm the diagnosis of DS in stillborn infants in whom it is suspected clinically, but in whom it cannot be confirmed cytogenetically. It also can serve as a screening procedure to select stillborns in whom fluorescent in situ hybridization of fixed tissues should be completed. An iliac index of 59 degrees differentiates between control and affected stillborns with the highest accuracy, but false positives persist above 55 degrees, and false negatives are common below 64 degrees. We recommend that a conservative cutoff value of 55 degrees be used if the radiographic data serve as the principal means of diagnosing DS in stillborn infants. A cutoff value of 64 degrees may be appropriate if the radiographic data are used to screen stillborn infants for fluorescent in situ hybridization studies.

Acetabulum↗
PubMed1997

Long-term survival in typical thanatophoric dysplasia type 1.

Thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always lethal neonatally, although a few previous reports have documented survival up to 4.75 years. We present a patient with survival beyond age 9 years and summarize his growth, development and medical history. The common Arg248Cys mutation in the extracellular region of fibroblast growth factor receptor 3 (FGFR3) was identified, eliminating the possibility that his long-term survival is attributable to an atypical mutation. This patient (and at least one other TD long-term survivor) have a rare skin disorder, acanthosis nigricans, which also occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.

Acanthosis Nigricans↗
PubMed1997

Unexpected familial recurrence in Angelman syndrome.

We report on two instances of familial recurrence of Angelman syndrome which, from pedigree analysis, appear incompatible with currently known mechanisms of inheritance of this disorder. In these two families, deletion-positive Angelman syndrome has recurred in cousins. Several established mechanisms for deletion-positive familial recurrence have been ruled out. In each family, molecular cytogenetic studies show typical chromosome 15 deletions, and DNA methylation analysis verifies the maternal origin of the deleted chromosomes in all four individuals. Since the mothers of the affected individuals in each family are not known to be related, these recurrences appear to be secondary to coincidental, de novo events. This conclusion is consistent with direct and indirect estimates of the population frequency of Angelman syndrome.

Angelman Syndrome↗
PubMed1997

Smith-Lemli-Opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome.

We have reassessed patient "S," one of the first 3 individuals recognized to have Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his physical, developmental, and behavioral manifestations. This reassessment provides formal evidence that this individual has the cholesterol biosynthetic defect which is thought to be the cause of Smith-Lemli-Opitz syndrome. Dietary manipulation appears to have had a beneficial effect on the patient's behavior and suggests that even in adults with this condition, dietary cholesterol supplementation may be indicated.

Adult↗
PubMed1997

Biophysical bases for delayed and aberrant motor development in young children with achondroplasia.

Achondroplasia, the most common skeletal dysplasia, is characterized by delayed and aberrant motoric development in childhood. Delays and aberrancy are secondary to the anatomical differences inherent in people with achondroplasia. We present a photographic essay documenting biophysical differences, aberrant pre-orthograde movement strategies, and selected adaptive techniques. A parental questionnaire assessed the presence of, predominance, and ages at which various types of pre-orthograde locomotion were observed. Fine and gross motor skills were assessed contemporaneously by use of the Denver Developmental Screening Test in 93 children with achondroplasia and were found to be more delayed than previously reported. Physicians, therapists, early-childhood educators, and parents should recognize that aberrant does not mean maladaptive and that different development is not defective development.

Achondroplasia↗
PubMed1997

Fine mapping of the nail-patella syndrome locus at 9q34.

Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1).

Chromosome Mapping↗
PubMed1996

Standard curves of chest circumference in achondroplasia and the relationship of chest circumference to respiratory problems.

Several pathogenetic factors, alone or in combination, may contribute to the increased frequency of respiratory complications in achondroplasia. It has been suggested that relatively small chest circumference sometimes may contribute. However, there are no published curves of chest circumference for age in achondroplasia with which to compare patients. Nor are there data relating chest circumference to overall size in achondroplasia. We present curves of chest circumference for males and females with achondroplasia from birth through age 7 years. Additional curves for chest circumference against height are also provided. Finally, we report some preliminary data regarding the possible association of chest size with respiratory signs and symptoms.

Achondroplasia↗
PubMed1996

Errors in the prenatal diagnosis of children with achondroplasia.

To provide data about the frequency of prenatal misdiagnosis in achondroplasia (Ach), we retrospectively abstracted data from 37 consecutive referrals of infants with Ach where ultrasound was performed prenatally. Nine of 37 (24 per cent) had a positive family history of Ach; all nine were correctly diagnosed prenatally. Of the 28 with no family history of Ach, 16 (57 per cent) were recognized to have abnormalities on ultrasound but none was given a definite diagnosis of Ach. Five families received an appropriate diagnosis of "most likely' Ach and four others were given a non-specific (but appropriate) diagnosis of some dwarfing disorder, not otherwise specified. In seven instances (25 per cent), an incorrect diagnosis of a lethal or very severe disorder was provided. These results illustrate the difficulty of making a specific prenatal diagnosis of Ach. In the face of the resulting uncertainty, physicians appear to elect to emphasize the most severe of alternative diagnoses. Given the homogeneity of mutations within the fibroblast growth factor receptor 3 (FGFR3) gene in the vast majority of patients with Ach, FGFR3 mutational analysis can be offered in every instance where a short-limb disorder is ultrasonographically detected in the latter stages of pregnancy. This would reduce the amount of incorrect and potentially harmful information provided to families.

Achondroplasia↗
PubMed1995

Natural history study of hereditary multiple exostoses.

Hereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances from long bones and which can cause a variety of orthopedic deformities. This study sought to further delineate the natural history of EXT. In addition, since previous studies have suggested that there are deviations from Mendelian expectations in EXT, including incomplete penetrance and a skewed sex ratio, we attempted to confirm or refute these suggestions. Both portions of the study were carried out through retrospective review of 43 affected probands and 137 of their affected relatives. Data are presented concerning frequency and severity of complications of EXT including short stature, sequelae of exostoses, occurrence of malignant degeneration of exostoses, and problems in pregnancy and delivery of affected females. Only 2.8% of the total affected population had experienced exostosis-related malignancy, an estimate which is considerably less than earlier reports would suggest. Penetrance was 100%. There was an excess of males within the entire affected population (104:76) and within identified probands (28:15). However, the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents). The excess of males appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin.

Adolescent↗
PubMed1995

Patterson-Lowry rhizomelic dysplasia: a possible second example.

We present a possible example of Patterson-Lowry rhizomelic dysplasia. If so, this is only the second reported individual with this disorder and the first instance of its recognition in a child. Clinical features in this child are compared with the other described individual and differential diagnosis is discussed. Primary features include rhizomelic foreshortening most markedly affecting the arms, limitation of shoulder abduction, mild generalized foreshortening of the long bones, mild short stature, coxa vara, and specific radiological features.

Body Height↗
PubMed1995

Genetic heterogeneity in multiple epiphyseal dysplasia.

Multiple epiphyseal dysplasia (MED) comprises a group of hereditary chondrodysplasias in which there are major anatomic abnormalities of the long tubular bones. The Fairbank and Ribbing types are the most frequently cited types of MED. They are primarily defined radiographically and are autosomal dominant conditions. Recently, MED in one family was shown to map to the pericentromeric region of chromosome 19 and is probably allelic to pseudoachondroplasia. We have tested linkage with six short tandem repeat markers from chromosome 19 to autosomal dominant MED in one four-generation family and to MED in a unique family with three of seven siblings affected and with unaffected parents. Autosomal dominant MED in family 1 was linked with a maximum LOD score, at D19S212, of 3.22 at a recombination fraction (theta) of .00. Linkage to chromosome 19 was excluded with MED in the other family, under both autosomal recessive and autosomal dominant, with either reduced-penetrance or germ line-mosaicism models. Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family. COL11A1 was excluded under a recessive model. We have confirmed linkage of autosomal dominant Fairbank MED to chromosome 19 and have demonstrated that MED is genetically heterogeneous.

Adult↗
PubMed1995

Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia.

Achondroplasia, the most common heritable skeletal dysplasia, may result in abnormality at the craniocervical junction, which is a potentially lethal problem in a subset of young infants with this disorder. We evaluated and followed an unbiased and unselected consecutive series of infants with achondroplasia, to better document the occurrence, frequency, and clinical presentation of craniocervical abnormalities. Of 53 prospectively ascertained infants, 5 were judged to have sufficient craniocervical junction compression to require surgical decompression. Intraoperative observation always showed marked abnormality of the cervical spinal cord, and all operated-on children showed marked improvement of neurological function. The most frequent clinical abnormalities within this subset were those expected for high cervical myelopathy. The best predictors of need for suboccipital decompression included lower-limb hyperreflexia or clonus, on examination; central hypopnea demonstrated by polysomnography; and foramen magnum measures below the means for children with achondroplasia. Infants with achondroplasia are at risk for potentially lethal sequelae of craniocervical junction abnormalities; selective intervention can be life and health saving, but individuals at high risk will be identified only if all affected infants undergo comprehensive assessment in infancy.

Achondroplasia↗
PubMed1994

Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community-based program for etiologic investigation of intrauterine deaths.

Although stillbirth is a common event, few programs have previously been established for the comprehensive etiologic investigation of intrauterine death. Fewer still have been prospective, unbiased in ascertainment, and consistent in protocol utilization. The Wisconsin Stillbirth Service Program was established in 1983 as a unique model for the investigation of the causes of stillbirth. This community-based, University-supported model for health care delivery is here described. Through it more than a thousand infants have been etiologically investigated. We demonstrate that a community-based program of stillbirth assessment can succeed, that compliance with recommended protocols is high and that a specific primary cause of fetal death can be demonstrated in about 40% of referrals. A majority of the established causes of intrauterine death are fetal etiologies. Furthermore, it appears that there are no substantial referral biases. Lack of such biases, together with the prospective, protocol driven nature of the program provides a unique population upon which to base estimates of the frequency of various etiologic diagnoses and classes and categories of cause.

Bias↗
PubMed1994

Wisconsin Stillbirth Service Program: II. Analysis of diagnoses and diagnostic categories in the first 1,000 referrals.

The Wisconsin Stillbirth Service Program has provided a mechanism for the collection and analysis of unbiased and representative information concerning stillborn infants. Generated diagnoses and diagnostic categories within the first 1,000 referrals (including 789 stillbirths) is summarized here. Among all referred stillborns, 24.5% were found to have an identifiable intrinsic fetal cause of death. Specific diagnoses were extraordinarily heterogeneous, with about 85 different processes identified with this group. No single diagnosis was found in more than 1 1/2% of the evaluated stillborns. Distribution by classes of fetal causes (as a percent of all fetal causes in stillborns) included malformation syndromes in 44%, single malformations and defined sequences in 34%, disruptions in 10%, and dysplasias in 3%. The heterogeneity of syndromic causes is illustrated, examples of previously undescribed syndromic processes provided and the problems experienced in generating specific diagnoses discussed. Specific single malformations, sequences, disruptions, and dysplasias are also tabulated and illustrated. Distribution by etiologic categories (as a percent of all fetal causes in stillborns) included defined sporadic conditions in 29%, cytogenetic aberration in 25%, presumed multifactorial processes in 12%, Mendelian disorders in 5%, and environmental events in less than 4%. A fourth of all fetal causes could not be sufficiently defined to allow for certainty in assigning a specific etiologic category. The materials summarized provide reference data regarding the frequency of classes and categories of fetal diagnoses generated from an unbiased and non-selected series of stillborns.

Female↗
PubMed1994

Lower mesodermal defects: a common cause of fetal and early neonatal death.

Among the first 1,130 referrals to the Wisconsin Stillbirth Service Program 17 infants have been recognized to share phenotypic characteristics involving the genital, urinary, lower gastrointestinal, and axial skeletal systems. The pattern of abnormalities identified appears to be limited to structures sharing a common embryologic origin. These features, for the most part, are shown to be non-randomly associated. No clearly definable sub-groups within this population are demonstrable. The pattern of abnormalities is defined to include abnormalities of the following structures as pathogenetically primary features: lumbosacral vertebrae, kidneys, ureters, uterus/fallopian tubes, vagina, bladder, urethra, adrenals, gonads, anorectum, external genitalia, and umbilical arteries. An embryologic mechanism is proposed which explains this non-random association as arising secondary to disruption of structures derived from the lower portion of the primitive intraembryonic mesoderm. The Lower Mesodermal Defects Sequence appears to be a rather common (and under-recognized) cause of stillbirth and immediate neonatal death.

Adrenal Glands↗
PubMed1993

Cranial nerve abnormalities in CHARGE association.

Many children with the CHARGE association have facial paralysis and feeding and swallowing difficulties. Indeed, facial paralysis and pharyngeal incoordination may be important diagnostic indicators of CHARGE association [Davenport et al., 1986a; Mitchell et al., 1985]. We describe an individual with dysfunction of multiple cranial nerves (Möbius sequence) and CHARGE association, a previously unrecognized combination. Our review of 150 patients from the literature and 13 patients from this center with CHARGE association documented that dysfunction of cranial nerves is frequent in CHARGE association, and that often cranial nerve abnormalities are multiple. Such multiple cranial nerve abnormalities may be the primary underlying cause for the facial paralysis, feeding difficulties and sensorineural hearing loss seen in many individuals with CHARGE association.

Abnormalities, Multiple↗