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Biomedical subjects

J L Frias

Publications and source records attributed to J L Frias.

At least 19 recordsLinked to original sources

Neuroradiology and clinical aspects of Usher syndrome.

We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.

Abnormalities, Multiple

Opitz BBBG syndrome: new family with late-onset, serious complication.

The Opitz BBBG syndrome is characterized by hypertelorism and (in male patients) hypospadias, in addition to a number of midline abnormalities: posterior laryngeal cleft, stridor, swallowing dysfunction, cardiac defects, imperforate anus, and urinary tract and CNS anomalies. Inheritance is autosomal dominant (McKusick number *145410) with partial male sex limitation in most pedigrees. We report a Dutch family with Opitz BBBG syndrome in which the proband developed late-onset symptoms of a structural laryngeal abnormality.

Abnormalities, Multiple

Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency.

Adolescent

Study of the etiology of deafness in an institutionalized population in Colombia.

To identify causative factors we screened 1,715 deaf individuals from 16 schools for the deaf in Colombia. We found evidence of environmental causation in 579 (33.8%) cases, genetic in 608 (35.4%), and in 528 (30.8%) we were unable to identify the etiology. The degree of hearing loss was severe to profound in 1,238 (72.2%), although in 987 (57.5%) of the deaf population studied the hearing impairment was not noticed until 2 to 5 years of age. The frequent association of deafness with other anomalies underscores the importance of a careful clinical and ophthalmologic evaluation in individuals with hearing loss. Our observations also emphasize the need for programs directed towards the prevention of hearing loss, including primary prevention as well as early diagnosis, investigation of possible genetic causes, and rehabilitation of deaf individuals.

Adolescent

Radiographic features of craniometadiaphyseal dysplasia, wormian bone type.

We describe the radiographic findings in two siblings with a previously unrecognized craniotubular bone dysplasia. We call this condition craniometadiaphyseal dysplasia, wormian bone type. Because the parents of the siblings are consanguineous, this is probably a genetically determined condition with an autosomal recessive type of transmission. The findings in the siblings are compared with those of a woman with the same condition, previously reported as an example of craniometaphyseal dysplasia. The combination of findings in these patients seems diagnostic: characteristic skull changes including multiple wormian bones; wide long tubular bones without normal metaphyseal flaring; wide short tubular bones without normal diaphyseal constriction and sometimes actual diaphyseal expansion; and wide ribs and clavicles.

Bone Diseases, Developmental

Usher syndrome: results of a screening program in Colombia.

Otological, ophthalmological and genetic studies were performed in 46 patients with Usher syndrome, identified through a screening program in Colombia. Of them, 69.6% had Usher syndrome type I, 26.1% type II, and 4.3% type III. Thirty-three patients showed profound deafness (71.7%), while 13 (28.3%) had moderate to severe hearing loss. The ophthalmologic manifestations showed marked variability. Although the majority of the patients had serious ocular impairment before age 20, 32.6% had good central visual acuity. The prevalence of Usher syndrome in Colombia, estimated at 3.2/100,000, warrants the implementation of screening programs in schools for the deaf and for the blind. Our study confirms that Usher syndrome shows no geographic or racial variation and that the disorder has a wide variability of expression and genetic heterogeneity. The large size of the families we have detected may provide important opportunities for further genetic studies, particularly in terms of the assignment of the locus and gene mapping.

Colombia

Partial duplication 1q: report of four patients and review of the literature.

Here we report on 4 unrelated patients with reciprocal translocations which resulted in duplication of the distal portion of chromosome 1q. Although the patients had certain non-specific malformations in common, our investigation and a review of the literature do not suggest the existence of a distinct phenotype due to this chromosome abnormality. We think that the coexisting deletion present in each of these patients is responsible for most of the observed differences in clinical manifestations. The variable phenotype makes clinical recognition difficult and precludes making a long-term prognosis.

Chromosome Aberrations

Clinical, cytogenetic, and molecular evaluation of a patient with partial trisomy 21 (21q11-q22) lacking the classical Down syndrome phenotype.

The clinical, cytogenetic, and molecular studies of an individual are presented here for the purpose of further characterizing what regions of chromosome 21q are essential for expression of the typical Down syndrome phenotype. This individual had a de novo, unbalanced translocation chromosome interpreted as: 45,XX,t(18;dup[21q]). Physical examination revealed mild manifestations, but not the typical phenotype of Down syndrome. The patient was studied using 20 single copy probes known to map to the 21q region. DNA polymorphism and dosage analyses showed triplication of loci D21S13 through D21S58 involving 21q11 to 21q22.1, and possibly involving the 21q22.2 region. Her clinical presentation, which did not include the classical findings of Down syndrome, suggests that regions distal to 21q22.1, when present in triplicate dose, account for the major manifestations of the classical phenotype. However, duplication of the area between the centromere and 21q22.1 may contribute to some of the other abnormalities in Down syndrome.

Adult

Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation.

An 8-year-old female child with mental retardation (MR), multiple congenital anomalies (MCA) and irregular pigmentation was shown to have karyotypic mosaicism involving chromosome 14 abnormalities. Four cell lines were found in both peripheral blood lymphocytes and skin fibroblasts and were represented by: a normal karyotype, an isopseudodicentric 14q [iso psu dic(14)], a ring 14 [r(14)], and a monosomy 14 [mono(14)]. Our results are compared with reported cases involving multiple abnormalities of specific chromosomes. Karyotypic mosaicism of comparable chromosome 14 abnormalities is rare, with only one known previous case. Detailed analysis of karyotypic mosaicism of rare chromosomal abnormalities is essential to determine meaningful correlations with specific patterns of malformation.

Abnormalities, Multiple

Association of pigmentary anomalies with chromosomal and genetic mosaicism and chimerism.

We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnormal pigmentation followed Blaschko lines. The literature contains at least 36 similar examples of an association between pigmentary anomalies and chromosomal mosaicism, as well as five examples of an association with chimerism. The pigmentary anomalies are pleomorphic, and the chromosomal anomalies involve autosomes and sex chromosomes. The pigmentation patterns are reminiscent of the archetypal paradigm seen in allophenic mice and demonstrate the clonal origin of melanoblasts from neural crest precursors. Patients with anomalous skin pigmentation, particularly when it follows a pattern of Blaschko lines, should be appropriately evaluated for a possible association with chromosomal or genetic mosaicism or chimerism.

Adolescent

New methods for quantitative and qualitative facial studies: an overview.

The clinical study of birth defects has traditionally followed the Gestalt approach, with a trend, in recent years, toward more objective delineation. Data collection, however, has been largely restricted to measurements from X-rays and anthropometry. In other fields, new techniques are being applied that capitalize on the use of modern computer technology. One such technique is that of remote sensing, of which photogrammetry is a branch. Cartographers, surveyors and engineers, using specially designed cameras, have applied geometrical techniques to locate points on an object precisely. These techniques, in their long-range application, have become part of our industrial technology and have assumed great importance with the development of satellite-borne surveillance systems. The close-range application of similar techniques has the potential for extremely accurate clinical measurement. We are currently evaluating the application of remote sensing to facial measurement using three conventional 35 mm still cameras. The subject is photographed in front of a carefully measured grid, and digitization is then carried out on 35-mm slides specific landmarks on the cranioface are identified, along with points on the background grid and the four corners of the slide frame, and are registered as xy coordinates by a digitizer. These coordinates are then converted into precise locations in object space. The technique is capable of producing measurements to within 1/100th of an inch. We suggest that remote sensing methods such as this may well be of great value in the study of congenital malformations.

Cephalometry

PhDs in pediatric departments.

A survey on PhDs in academic pediatric departments was sent to members of the Association of Medical School Pediatric Department Chairmen (70% responded). Significant numbers (14.5%) of pediatric faculty members hold PhDs. Another 3.6% hold PhDs/MDs. Research is their major responsibility in every subspecialty except psychology. The majority of PhDs (51%) are assistant professors (8% tenured) in contrast to 37% of MD faculty (14% tenured). The majority of PhDs at full professor (56%) are tenured compared with only 44% of MDs. Separate criteria exist for promotion for PhDs in 42% of departments. For promotion to associate professor, the mean number of refereed publications is 18 (median, 15); for full professor, the number ranges from ten to 50 (median, 40). Extramural research funding carries the highest weight in evaluating research efforts. PhDs could impact significantly on long-range planning in academic pediatric departments.

Faculty, Medical

Magnetic resonance imaging in the assessment of medullary compression in achondroplasia.

Children with achondroplasia may be at increased risk of developing apneic episodes and of dying unexpectedly. The risks seem to be related to neural axis compression by an abnormal cranial base and may be complicated by the development of hydrocephalus. We used magnetic resonance imaging to study five children with achondroplasia. All of them demonstrated a discrepancy between the size of the brain stem and the foramen magnum. Comprehensive prospective assessment of infants with achondroplasia, including the use of new imaging techniques, will provide important information concerning the natural history of the relationship of the neural axis to the bony posterior fossa and upper cervical spine in this condition. It may also help to identify those patients at risk before the development of life-threatening medullary compression.

Achondroplasia

Mild expression of the Pfeiffer syndrome.

The acrocephalosyndactylies are a group of conditions with a wide variability of expression. We report a patient with features of the Pfeiffer syndrome (acrocephalosyndactyly type V), initially believed to be a new mutation in her family. Further examination of her mother demonstrated abnormalities of her right thumb which we believe may represent mild expression of the Pfeiffer syndrome. This observation illustrates the variability of phenotypic expression in the Pfeiffer syndrome and underscores the importance of careful investigation of parents and other family members when evaluating individuals with this condition.

Acrocephalosyndactylia

Apparent G syndrome presenting as neck and upper limb dystonia and severe gastroesophageal reflux.

We have studied a 3-month-old boy with severe gastroesophageal reflux, feeding difficulties, neck and upper limb dystonia, abnormal ears, normal genitalia, and anatomically apparently normal larynx and trachea. Initially diagnosed as suffering from Sandifer "syndrome," he was treated with a gastrostomy and Nissen fundoplication. However, his characteristic facial appearance subsequently led to the diagnosis of G syndrome.

Abnormalities, Multiple