Isochromosome 12p mosaicism (Pallister mosaic aneuploidy or Pallister-Killian syndrome): report of 11 cases.

We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the isochromosome is usually absent in cultured lymphocytes but present in fibroblasts. The patients range in age from a 22-week-gestation fetus to a 45-year-old man. They have a distinct pattern of anomalies which enables one to make a diagnosis based on clinical manifestations alone. Craniofacial manifestations include "coarse" face with prominent forehead, sparsity of scalp hair, hypertelorism, epicanthal folds, flat bridge of nose, and highly arched palate. Affected newborn infants are profoundly hypotonic with sparsity of scalp hair especially bitemporally and a prominent forehead. Most have accessory nipples. Birthweight and growth parameters are usually normal; however, some newborn infants are unusually large. In infancy, the facial appearance becomes "coarse," hypotonia persists, and seizures may occur. As adults, growth may be normal, scalp hair is thicker and the mandible becomes prominent. Most have a generalized pigmentary dysplasia which may be evident with a Wood's lamp only. All cases have been sporadic and there is no consistent pattern of advanced parental age.

Familial ovarian dysgenesis in 46,XX females.

Three phenotypic female sisters in a sibship of four sisters and one brother were found to have pure ovarian dysgenesis, which was confirmed by the finding of streak gonads at laparotomy in two of the three sisters who presented with amenorrhea and lack of secondary sexual characteristics. No evidence of any other congenital anomaly was found in any of these sisters. Pure gonadal dysgenesis syndrome distinguishes a group of women with primary gonadal failure with amenorrhea whose heights are over 152 cm and who are without either webbed necks or any of the other somatic anomalies that are characteristic of Turner's syndrome. Cytogenetic studies revealed a normal female (46,XX) karyotype in all the affected members. Endocrine studies indicated that the affected sisters had elevated FSH and LH values with decreased plasma estradiol and urinary estrogen determinations. This is the second report of a family with 46,XX karyotype that meets all the criteria for the pure gonadal dysgenesis syndrome. The multiple affected sibs suggests an autosomal recessive mode of inheritance.

Endocrine-metabolic relationships in patients with leprechaunism.

Leprechaunism is a rare, heritable syndrome, associated with multiple dysmorphic and pathologic features, suggestive of an endocrine dysfunction. Few endocrine and metabolic studies have been obtained because of the rarity of the syndrome, and the small size and early demise of these infants. The authors present here the clinical, anatomic, and endocrine-metabolic studies of three patients, with a view toward careful delineation of the syndrome and further characterization of the metabolic defect.The most striking and consistent metabolic derangements present in all of these patients were fasting hypoglycemia (less than 20 mg/dL), postprandial hyperglycemia (more than 250 mg/dL), marked hyperinsulinemia (more than 2000 µU/mL), and severe insulin resistance (less than a 20 percent decrease in blood sugar with 0.3 to 1.0 U/kg of regular insulin IV). Hyperinsulinemia was observed in response to oral feedings and glucose infusion, and after tolbutamide. Insulin secretion was less marked with amino acid infusions. Normal increments in blood glucose occurred following alanine, galactose, and glycerol. Glucagon caused a rise in glucose 4 hours after a meal, but no response was seen after a 12-hour fast. Pituitary, gonadal, and adrenal hormone levels were normal, and there was a normal response pattern to GnRH and TRH. Hyperinsulinemia would appear to be the biochemical hallmark of this disease. Our previous studies were suggestive of a postreceptor defect in insulin action. The present endocrine-metabolic studies are compatible with this hypothesis. Interaction of supraphysiologic concentrations of plasma insulin with growth factor receptors, this may provide a partial explanation for some of the dysmorphic features seen in the disorder.

Diphenylhydantoin teratogenicity: ocular manifestations and related deformities.

This patient illustrates a classical case of what many pediatricians call the diphenylhydantoin teratogenic syndrome. It suggests the possibility of an additional ocular finding of retinoschisis and optic nerve abnormalities which could conceivably have a teratogenic basis. The effects of epilepsy and diphenylhydantoin on these formations is discussed.

Familial multiforme ventricular extrasystoles with short stature, hyperpigmentation and microcephaly-a new syndrome.

A previously undescribed syndrome with ventricular extrasystoles and presumed cardiac syncopy, hyperpigmentation, short stature and microcephaly in a mother and son was presented. Physiologic and pharmacologic studies suggest that the mechanism of the ventricular arrhythmia depends on multiple and reentrant pathways occurring below the bundle of His.

Children with Marfan's syndrome and pectus excavatum.

Pectus excavatum occurs in two thirds of children with Marfan's syndrome. The characteristics of seven children with Marfan's syndrome and pectus excavatum were compared with those of 38 children who had pectus excavatum without Marfan's syndrome. The children with Marfan's syndrome presented later, had progressive defects, and were more likely to have wound problems; however, acceptable cosmetic and functional results after chest wall repair were obtained in the patients with Marfan's syndrome.

Problems in counseling the epileptic mother.

Epileptics, medical colleagues, and the public must be educated regarding the teratogenicity of anticonvulsants to the developing fetus. To prevent the serious problems of the fetal hydantoin-barbiturate syndrome, epileptic mothers must be given counseling. There are numerous problems encountered in counseling any individual with genetic disorders and dull intellect. More than the usual time and effort and cooperation of many agencies is needed to achieve success in counseling.

Chromosome 13 long arm interstitial deletion associated with features of Noonan phenotype.

A 22-year-old Caucasian mildly retarded male presented with facial features of high nasal bridge, prominent supraorbital ridges, some malar hypoplasia, prognathism, short philtrum, and prominent full lips associated with shortness of stature, nuchal webbing, and esotropia. His cardiac exam and genital development were normal. The diagnosis of Noonan syndrome had been previously entertained. A chromosome analysis revealed an interstitial deletion of a chromosome 13 at (q21.32q22.3).

Melanotic neuroectodermal tumor of infancy and fetal hydantoin syndrome.

Fetal hydantoin syndrome (FHS), a characteristic pattern of altered growth and development, has been well described in recent years in offsprings of epileptic mothers taking phenytoin or other hydantoin anticonvulsants during the gestational period. Recent reports of neuroblastoma in three patients with the FHS further raise the questions of the "oncogenic effect " of hydantoin compounds. A case of melanotic neuroectodermal tumor of infancy (MNTI) has been studied clinically and pathologically including light microscopy, histochemistry, and electron microscopy. This case strengthens the evidence for the teratogenic and oncogenic effects of hydantoin compounds and we believe that it represents the first reported case of FHS associated with MNTI. It would be most important from a clinical standpoint to carefully scrutinize individuals with the FHS for neoplasias. Furthermore, detailed gestational drug history in children with neuroblastoma and other neoplasias should be carefully searched for, with the hope of clarifying the definitive oncogenic effect of hydantoin compounds.