James J. Nora

A syndrome of multiple congenital anomalies associated with teratogenic exposure.

A study of 19 patients with multiple congenital anomalies described by the acronym VACTERL (Vertebral, Anal, Cardiac, Tracheoesophageal, Renal, and Limb) revealed exposure at the vulnerable period of embryogenesis to a progestogen/estrogen compound or a progestogen alone in 13 patients. These hormones were taken as a “pregnancy test,” and for a variety of other reasons. Comparison of VACTERL patients with paired and matched controls, one group with chromosomal anomalies (other than Down syndrome) and another group with functional murmurs, revealed a significant difference with respect to exposure to hormonal contraceptives. The multiple anomalies of skeletal, cardiovascular, and gastrointestinal structures recapitulate the systems involved in the thalidomide syndrome, but present a variation of the pattern. Until more definitive data are available it would be prudent to emphasize the need to verify the absence of pregnancy before initiation of oral contraception and to discontinue hormonal agents as tests...

Etiologic Factors in Congenital Heart Diseases

Clues to the etiology of congenital heart disease have clustered in the two areas of genetic and environmental factors. After stating and briefly discussing the multifactorial hypothesis for the etiology of congenital heart disease – the genetic-environmental interaction – the author presents his personal experience in etiologic investigation.

Fusion of two apparently intact human X chromosomes

SummaryCytological studies have been presented from a 15-year-old girl with short stature and failure of puberty. Buccal mucosa preparations revealed X-chromatin mass approximately double in size of that of a normal female. Leukocyte metaphases suggested a two cell line composition of the patient. One population of cells conformed with 45,X chromosome distribution. The chromosome complement of her other cell line had a modal number of 46. In this cell line a “C” chromosome was replaced by an exceptionally large submetacentric chromosome. This abnormal element exhibited late DNA replicating pattern. G-banding study revealed that the abnormal chromosome was produced as a result of fusion involving telomeric ends of long arms of 2 intact X chromosomes. This translocation X was bearing 2 C-banded areas; one around the centromere and the other at the distal end of the long arm. The distal C-band area did not show any evidence for centromeric function. It appears that a centromere becomes latent in the presence of another centromere in a translocation bearing 2 total chromosomes. Such a change of state in the additional centromere is vital for the stability of the translocation chromosome.

His bundle recording in progressive external ophthalmoplegia

Summary A teen-age girl with a 5 year history of PEO was noted to have a progressive disturbance of atrioventricular conduction with LAD, RBBB, and intermittent second degree heart block of Mobitz type II. His bundle recordings revealed a prolongation of the H-V conduction time interval and the development of Mobitz type II second degree block following atropine administration. A permanent demand cardiac pacemaker was implanted and successfully paced the patient during episodes of complete heart block which subsequently developed.