In this edition of the textbook, the pathologic changes related to in utero diethylstilbestrol (DES) exposure have been incorporated into the chapter on diseases of the vagina. This has been done in order to present an integrated review of various disease entities primarily affecting the vagina. However, for the sake of clarity, the DES pathology is presented in a separate section, as the various benign and malignant aspects of this entity are closely interrelated and involve other sites in the genital tract besides the vagina.

Diseases of the Vagina

A family is described in which the mother has an 18p- chromosome, one normal 18, and a probable i(18p) One of the daughters of this woman inherited the 18p- chromosome, and her phenotype resembles that of other 18p- cases The other daughter inherited the presumed i(18p) chromosome, and her phenotype resembles that of some cases with extra, small metacentric chromosomes The clinical, chromosomal, and familial evidence suggest that these abnormal chromosomes originated in the occurrence of one transverse break of the centromere and subsequent misdivision of a chromosome 18 in an earlier generation of this family According to this interpretation, the mother is trisomic for 18p, one daughter is monosomic and the other daughter is tetrasomic for this chromosomal region

Origin of a small metacentric chromosome: Familial and cytogenetic evidence

Severe toxicity from ethanol, manifested as coma, occurs at lower blood alcohol concentrations in young teenagers than in adults. Coma, vomiting and hypothermia are the commonest symptoms in young teenagers intoxicated by alcohol. The biochemical disturbances in children 11-16 years of age with alcohol intoxication resemble those of adults. Mild acidosis of a respiratory and metabolic origin and mild hypokalaemia are common findings in young teenagers. Young teenagers eliminate ethanol at the same rate as adults, whereas preschool age children are reported to eliminate ethanol twice as fast. The effect of ethanol on the state of consciousness is directly proportional to the blood alcohol concentration. Among small children the risk of hypoglycaemia is increased. Data on family history, social status, drinking habits, and children's motives for getting drunk are also of clinical importance. Fluid replacement with glucose-containing fluids and follow up are generally the only treatments needed for complete recovery. When children and adolescents are healthy, well-nourished and have not fasted, no severe complications are expected.

Acute alcohol intoxication among children and adolescents.

Since 18p- was first described in 1963, much progress has been made in our understanding of this classic deletion condition. We have been able to establish a fairly complete picture of the phenotype when the deletion breakpoint occurs at the centromere, and we are working to establish the phenotypic effects when each gene on 18p is hemizygous. Our aim is to provide genotype-specific anticipatory guidance and recommendations to families with an 18p- diagnosis. In addition, establishing the molecular underpinnings of the condition will potentially suggest targets for molecular treatments. Thus, the next step is to establish the precise effects of specific gene deletions. As we look forward to deepening our understanding of 18p-, our focus will continue to be on the establishment of robust genotype-phenotype correlations and the penetrance of these phenotypes. We will continue to follow our 18p- cohort closely as they age to determine the presence or absence of some of these diagnoses, including spinocerebellar ataxia (SCA), facioscapulohumeral muscular dystrophy (FSHD), and dystonia. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. Mouse models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development.

A review of 18p deletions

A mentally and physically retarded boy with a 46,XY,ring (4) (p16q35) chromosome complement is described Chromosome banding showed that the amount of chromosome material deleted from the ring chromosome 4 was minimal, apparently no more than the telomeres Chromosomal aberrations appear to be restricted to the production of double-sized dicentric rings, and aneuploidy The mosiacism resulting from the behavioural peculiarities of ring chromosomes is described as dynamic mosaicism It is suggested that the clinical features associated with this ring chromosome are more likely to be the result of the effects of a diploid/monosomy 4/polysomy 4 mosaicism than to the deficiency of the telomeric regions of the chromosome

https://jmg.bmj.com/content/jmedgenet/14/3/228.full.pdf

Ring chromosome 4.

A 10-year-old mentally and physically retarded girl has a mosaic ring-4 chromosome. The number of ring chromosomes in her peripheral blood preparations has increased from 9% to 72% in the past seven years. The child had a low birth weight and has had several phenotypic changes.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=PEDS&articleId=505702&pdfFileName=archpedi_128_3_015.pdf

A Child With a Ring-4 Chromosome (46,XX/46,XX,r 4)

Ethanol poisoning. Case report of coma, convulsions and death in a 2-year-old following ethanol ingestion

A small black girl with a deletion of chromosome 18 is described. She is mentally retarded and small for her age, and has severe dental decay, hypertelorism, and epicanthic folds. Her IgA is normal. Her bone age is retarded.

A Short, Retarded Child with a Deletion of the Short Arm of Chromosome 18 (18p-)

and growth of basal cells of the vaginal mucosa at all ages appears to be estrogenically controlled.2 It is already well documented that the vaginal epithelium of the newborn female shows changes due to estrogens.I, 3, 9, 16 In the maternal circulation the level of free estrogen begins to rise a few weeks before the onset of labor., This estrogen appears to cross the placenta and enter the blood stream of the fetus,-’ where it causes the squamous epithelium of the vagina of the newborn female to take on a mature appearance. This paper describes a study made to determine how long after birth the cellular changes induced by estrogens can be demonstrated in the newborn vagina.

Charles E. Parker

Papers

A Child With a Ring-4 Chromosome (46,XX/46,XX,r 4)

Ethanol poisoning. Case report of coma, convulsions and death in a 2-year-old following ethanol ingestion

A Short, Retarded Child with a Deletion of the Short Arm of Chromosome 18 (18p-)

The effect of maternal estrogens on the vaginal epithelium of the newborn.

Chloropropamide Poisoning A Case Report of Accidental Ingestion in a Two-Year-Old Child