Biomedical subjects
Publications and source records attributed to D Donnai.
We describe a family in which two boys with Norrie disease have a deletion of the DXS7 locus. The deletion does not extend as far distally as the OTC or DXS84 loci. A full clinical description of the patients is given to help establish the range of manifestations of Norrie disease. There is no evidence of any other X linked disease in our patients.
We present a female infant with multiple joint dislocations, flat facies, cleft soft palate, redundant neck skin, pulmonary hypoplasia, and skeletal abnormalities.
The monoclonal antibody (MAB) 60.3 reacts with the beta chain (CD18) of lymphocyte function associated antigen (LFA-1), encoded by a gene on chromosome 21. We have used 60.3 to measure the expression of CD18 on lymphoblastoid cell-lines derived from persons with Trisomy 21 (Down syndrome) by quantitative fluorescence flow cytometric analysis. This showed that CD18 expression is increased on Trisomy 21 compared with normal cells, whereas neither HLA-class I, nor transferrin receptor expression are significantly affected. Similar results were obtained with the CD18 MAB MHM 23, and with the CD11a MAB MHM 24 (LFA-1 alpha). These results suggest that the increase in CD18 expression by Trisomy 21 cells is due to gene dosage, and could influence the immune status of persons with Down syndrome.
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We report on 11 new cases of Proteus syndrome to illustrate the broad range of the phenotype in this hamartomatous dysplasia. The cardinal manifestations of this sporadic disorder are hemihypertrophy, macrodactyly, exostoses, scoliosis, cavernous hemangiomas, lipomas, linear sebaceous nevi, and deeply rugated soles of the feet. Intelligence is usually normal. The differential diagnosis includes Klippel-Trenaunay-Weber and partial lipodystrophy syndromes.
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The non-technical aspects of delivery of prenatal diagnostic services deserve consideration. Communication with the patient and her partner about their risks of fetal abnormality, the risks of tests and the interpretation of results is essential if the couple are to make the right choices for themselves. Some results of prenatal tests are easy to interpret but others are more difficult either because the clinical consequences cannot be predicted or because the laboratory results are 'borderline' or could be artifactual. Further tests to clarify the situation may be necessary and expert help sought from several disciplines. Staff involved in the care of a woman undergoing termination of pregnancy should be willing to participate in the procedures sympathetically. Post-termination examination of the aborted fetus is necessary both for genetic counselling and quality control for the tests employed. Throughout the various stages of prenatal diagnosis, support should be provided for the couple; this is particularly necessary for those who have had a previous abnormal baby. For those undergoing termination of pregnancy, skilled help should be offered to minimize long-term adverse sequelae.
One hundred and sixty nine patients with anorectal malformation were studied: there were 108 boys, 60 girls, and one case of intersex. Low malformations were more common in both sexes. Over half the subjects had associated malformations. These were more common in the group with high malformations. There was no difference between the sexes in this respect. A family history of similar malformation was found in 15 cases (9%). Where anorectal malformation was the only abnormality in the family an autosomal dominant mode of inheritance was likely, except in one case where there was consanguinity. Where there were associated malformations no single mode of inheritance emerged. Two families with probably hitherto unrecognised recessive syndromes are described. In most cases of anorectal malformation the recurrence risk is low. Multiple associated malformations may indicate recessive inheritance and subsequent pregnancies should be regarded as high risk and full antenatal investigative facilities provided.
Four infants who were exposed to sodium valproate or valproic acid during pregnancy are described. Common facial features in the three surviving infants include epicanthic folds, a flat nasal bridge, a broad nasal base, anteverted nostrils, a shallow philtrum, and a thin upper lip with a thick lower lip. Ridging of the metopic suture, congenital heart defect, postaxial polydactyly, and hypospadias were additional features in individual cases. In agreement with previous authors, we feel that there is a distinctive 'fetal valproate' phenotype.
The clinical features of the multiple pterygium syndrome are multiple congenital joint contractures, multiple skin webs, camptodactyly, vertebral anomalies, short stature, ptosis, and antimongoloid eye slant. We present 11 new cases to show the evolution of the full phenotype from birth and to confirm autosomal recessive inheritance. We emphasise morbidity secondary to respiratory impairment and that conductive deafness may be part of the syndrome.
A three generation family with orofaciodigital syndrome type I is described. Several family members had been thought to suffer from autosomal dominant polycystic kidney disease but examination of the proband led to establishment of the correct diagnosis. The genetic implications for the offspring of the affected women and other family members were significantly altered.
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A further case of a syndrome of pre- and postnatal growth retardation, characteristic face, and unusual palmar creases is described. This child also had hypoplasia of labia majora and minora, deafness, and head nodding. Apparently sporadic occurrence in this family does not rule out autosomal recessive inheritance of this syndrome first described by Pitt, Rogers, and Danks in 1984.
Three cases are reported of a lethal multiple congenital anomaly syndrome. The infants had moderate limb shortening, joint contractures, polydactyly, and the two with male karyotypes had female external genitalia. Internal anomalies included unilobular lungs, hypoplasia of the anterior portion of the tongue, and renal hypoplasia.
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Fifty-five fetuses with a pre-termination diagnosis of neural tube defect or hydrocephalus were examined. Termination was carried out on the basis of an elevated amniotic alpha-fetoprotein in 24 and on ultrasound examination in 31. Although pre-termination diagnosis was confirmed in 45 cases, a new or more refined diagnosis was made in 10. There was a high incidence of non-neural tube malformations. Fetuses terminated in a prenatal diagnosis screening programme should always be examined to establish the exact diagnosis for the provision of recurrence risks for genetic counselling and as a quality control for the test involved.
We report on three unrelated children with neonatal radiological characteristics of the Weissenbacher-Zweymüller (W-Z) syndrome. Subsequently, they developed the Marshall syndrome. The relationship between the W-Z, Marshall, and Stickler syndromes is discussed.