Robert L. Summitt

Familial Male Pseudohermaphroditism without Gynecomastia Due to Deficient Testicular 17-Ketosteroid Reductase Activity

Abstract To evaluate possible 17-ketosteroid reductase deficiency, we studied two sisters with primary amenorrhea, hirsutism, clitoral enlargement and a 46,XY karyotype, who lacked breast development. Plasma luteinizing hormone, follicle-stimulating hormone and urinary 17-ketosteroids were elevated in both subjects. Plasma Δ4-androstenedione was seven to nine times greater than normal, whereas plasma testosterone was low or in the low-normal male range. Spermatic venous plasma of Case 2 contained increased amounts of Δ4-androstenedione and estrone and subnormal amounts of testosterone and estradiol, findings consistent with testicular 17-ketosteroid reductase deficiency. In vitro incubation of testicular tissue of Case 2 confirmed a partial defect in testicular 17-ketosteroid reductase activity and documented increased 3β-hydroxysteroid dehydrogenase activity. Failure of breast development was probably due to lower estrogen levels than in previously reported cases. We conclude that testicular 17-ketostero...

Apparently balanced de novo translocations in patients with abnormal phenotypes: report of 6 cases.

Six patients have been ascertained because of abnormal phenotypes but with apparently balanced de novo translocations. Five of them were mentally retarded with multiple congenital anomalies. The sixth patient had normal mental development but revealed ambiguous genitalia and multiple congenital anomalies. No syndromal diagnosis was possible in any of the six cases. The appearance of apparently balanced reciprocal translocations in association with abnormal phenotype may be coincidental, or the two may be causally related. If the latter is true, the causal relationship may be based upon: I) a submicroscopic chromosomal loss, 2) position effect, or 3) a mutation at the site of the break in one or both translocated chromosomes.

Septic arthritis in childhood

Fifty-two cases of nontuberculous purulent arthritis seen at the Tobey Hospital during a 16 year period following the introduction of antibiotic therapy were reviewed. The clinical picture was found to be a consistent one with only one or two joints involved. There was usually high fever, leukocytosis, and severe pain, tenderness, and swelling of the involved joints. Early arthrocentesis with attempts to isolate the causative organism is important. Although antibiotic therapy has virtually eliminated the mortality from septic arthritis, significant residual disability occurs, especially when the hip is involved. Methods to facilitate early diagnosis and treatment are discussed.

X-autosome translocation in normal mother and effectively 21-monosomic daughter

A phenotypically normal mother carries a balanced X-21 translocation. Autoradiography of the mothers cells reveals that in all cells the normal X is late replicating. Her only pregnancy produced like-sex twins, one of whom is phenotypically and karyotypically normal. The co-twin is mentally retarded and has multiple anomalies. Her karyotype is 46,XX,der(21),t(X;21)(q11;p11?)mat. In the majority of informative cells from the daughter, one normal X and the entire X t replicate late. This maintains X dosage compensation, but results in effective monosomy 21. The phenotype of the infant is similar to others with 21q−.

Minor chromosome variations and selected heteromorphisms in 200 unclassifiable mentally retarded patients and 200 normal controls.

SummaryLymphocyte chromosome preparations from 200 mentally retarded children and 200 normal adult controls were analyzed by G-, Q-, and C-banding techniques for minor chromosome variations (G and Q) and selected heteromorphisms (G and C). Minor variations scored included inv(9), prominent or decreased short arms and/or satellite on acrocentric chromosomes, and 17ph. C heteromorphisms analyzed included those involving 1qh, 9qh, and 16qh regions. Length variations of Yq were scored on G-banded karyotypes. No significant differences in frequencies of scored minor variations or heteromorphisms were noted between the retarded and control populations.

Incidence of nickel-induced sister-chromatid exchange☆

Nickel is a recognized carcinogen to which the general population is being increasingly exposed. A nickel-induced alteration in the incidence of sister-chromatid exchanges in cultured lymphocytes has been investigated. Human lymphocytes from a single donor were cultured in media containing various concentrations of nickelous chloride from 10(-6) to 10(-3) M and a control culture containing no added nickel. A significantly increased incidence of exchanges over background was induced at 1.19 x 10(-4) M as indicated by a Students t-test. A concentration/response curve was generated up to 5 x 10(-4) M where the nickel concentration was lethal to the cells. The nickel response was analyzed by a chi-square test for any variation in location of activity across the karyotype and no differences were detected. The background incidence did vary from a uniform distribution across the karyotype with increasing incidences in chromosomes 1 and 2 and those of the B group, and decreased incidences in the E, F, and G groups.

Balanced reciprocal X-4 translocation in a female patient with early secondary amenorrhea

Balanced translocations involving an X chromosome and an autosome have been infrequently reported. A patient with a balanced X-autosome translocation 46,X,rcp(X;4)(q26;q21) who exhibited early secondary amenorrhea and gonadal dysgenesis is described. In an effort to explain the varied phenotypic expressions encountered in female cases of balanced X-autosome translocations, evidence will be provided to suggest an extension of the minimal limits of the critical region in the long arm of the X chromosome from A-B, as described by Sarto and associates, to new minimal limits C-D.

Polycystic Ovarian Disease, Maturation Arrest of Spermiogenesis, and Klinefelter’s Syndrome in Siblings of a Family with Familial Hirsutism *

A family with hirsutism in five generations in which polycystic or bilaterally enlarged ovaries were documented in three different sibships of two generations is described. Two brothers of one of the women with polycystic ovaries had a low or low-normal plasma follicle-stimulating hormone level and one of these had oligospermia due to maturation arrest of spermiogenesis. A third brother had Klinefelters syndrome. Other abnormal features in the family included precocious adrenarche, beardless males, eunuchoidism, and prepubertal grand mal seizures.

Salicylate intoxication in children—experience with peritoneal dialysis and alkalinization of the urine

Thirteen children with salicylate intoxication were studied. Seven patients were treated with intravenous fluids and alkali alone and six were treated with a combination of intravenous fluid and alkali and with intermittent peritoneal dialysis by means of 5 per cent albumin in an isoosmotic buffer. With full cognizance of its potential dangers, liberal amounts of sodium bicarbonate were used and no complications were encountered. As has been shown by others, sodium bicarbonate promoted renal excretion of salicylate. However, the combination approach was significantly more effective in removing salicylate from the body. The additional use of peritoneal dialysis is recommended in the treatment of those patients in whom more rapid removal of salicylate is desirable.

A cytogenetic survey of 200 unclassifiable mentally retarded children with congenital anomalies and 200 normal controls

SummaryA cytogenetic survey was carried out on 200 patients with mental retardation and multiple congenital anomalies, and on 200 normal adult controls. Patients with a known syndrome were excluded from the survey. Chromosome analyses were carried out on ‘blind-coded’ slides using the ASG banding technique as the routine stain. After the initial analyses (at least 15 cells per person) the slides were decoded, destained and reused for C and Q band polymorphism studies.Five major chromosome abnormalities were detected in the patient group during the survey. They included three patients with de novo, apparently balanced, reciprocal translocations, karyotypes 46,XY,rcp(3;16)(q21;p12); 46,XX,rcp(5;8)(p15;q22); and 46,XX,rcp(5;12)(p11;q24); one with karyotype 47,XX,+mar and one with karyotype 46,XX,der(13),t(13;?)(q34;?). One additional patient whose karyotype in lymphocytes was 46,XX,inv(9)(p11;q13) was found to have a mosaic karyotype 46,XX,inv(9)(p11;q13)/46,XX,inv(9) (p11;q13),der(12),t(12;?)(p13;?) in cultured skin fibroblasts. None of the 200 controls had a major chromosome abnormality.From the combined results of this and previous surveys it is now apparent that about 6.2% of the unclassifiable mentally retarded patients with three or more congenital anomalies and about 0.7% of the controls reveal major chromosome abnormalities.