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The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by Alfi et al. (1980). This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.

Cytogenetic investigation was carried out on 231 female patients referred for suspected sex chromosome abnormality. Cases were classified into five groups according to reason for referral and chromosome abnormality frequency was estimated. The overall frequency of abnormal karyotypes was 38.5%. The rate of positive identification of chromosome abnormality ranges from 0 in patients with secondary amenorrhoea to 80% in those with Turner phenotype. Our data demonstrate that the indications for referral of female patients with suspected sex chromosome abnormality are not only primary amenorrhoea alone or short stature and primary amenorrhoea without Turner stigmata, but also short stature of unknown etiology without any additional anomaly during childhood.

Eleven patients with the so-called Cat Eye syndrome are reported including a more detailed description of the original cases reported by Schmid and Fraccaro. All cases had, in addition to a normal karyotype, a small extra G-like chromosome which appeared to be an isochromosome for the juxtacentromeric region (pter to q11) of an acrocentric chromosome. None were mosaics. Clinical findings and further cytogenetic studies in a few cases suggest that these markers probably derive from a No. 22 chromosome. Characteristic features of the Cat Eye syndrome in these 11 patients and those reviewed from the literature are: ocular coloboma which may involve the iris, choroid and/or optic nerve, preauricular skin tags and/or pits which are probably the most consistent feature, congenital heart defect, anal atresia with a fistula, renal malformations such as unilateral absence, unilateral or bilateral hypoplasia, and cystic dysplasia, and antimongoloid position of eyes. Intelligence is usually low-normal, although moderate retardation is also seen. There is great variability in the clinical findings ranging from near normal to lethal malformations. Less frequent, but also characteristic findings are: microphthalmia, microtia with atresia of the external auditory canal, intrahepatic or extrahepatic biliary atresia and malrotation of the gut. Direct transmission of the marker from one generation to the other was observed in both sexes. In those families, there was considerable variability in the clinical findings between affected family members. These cases show that there is a bias of ascertainment for patients who have the more striking malformations, especially those with ocular coloboma and anal atresia, a combination which appears to be present in only a minority of cases. Many mildly affected patients probably remain undetected. It is proposed that the term Cat Eye syndrome should be applied only to cases with trisomy or tetrasomy of not more than 22pter to q11 and without additional duplication or deletion of another autosomal segment.

The development of prenatal diagnosis in Italy was made difficult by the restrictions of the old abortion law and only in recent years has a consistent number of cases been investigated. We report the experience on prenatal chromosome diagnosis of ten Italian centers participating in a collaborative study on 4952 diagnoses performed from 1972 to 1980. The main indication groups were: advanced maternal age (2882 cases), previous child with chromosome anomaly from parents with normal karyotype (847 cases), and chromosome anomaly in one parent (97 cases). The other indications for amniocentesis, including cases without a cytogenetic risk, have been assembled into a "miscellaneous" group (1126 cases). We found 125 abnormal fetal karyotypes (2.5%) of which 89 were unbalanced (1.8%). The frequencies and types of chromosome anomalies are reported in detail for each indication group and are compared with the corresponding one from the European Munich Conference. The great majority of these Italian data were not included in the Munich report.

Chromosome analysis of a 15-day old boy with multiple malformations revealed a partial deletion 12(p11;p13).

Three subjects from 2 unrelated families with partial duplication of 17q, derived from a reciprocal parental translocation between chromosomes 11 and 17 with different breakpoints, are described. A female patient from one family with a 46,XX,-11,+der(11),t(11;17)(q24;q23.2)pat chromosome complement had died at 2 months of age. In the second family, a male propositus and a subsequent fetus, identified by cytogenetic prenatal diagnosis, showed a 46,XY,-11,+der(11),t(11;17)(q2505,q24.3) mat chromosome complement. Twelve other cases involving partial duplication of chromosome 17 have been reported, 11 of these derived from a balanced translocation, and 1 was a duplication. All these cases showed psychomotor and mental retardation, cranial contour anomalies, micrognathia, bulbous nose, short neck, skeletal anomalies, and CNS defects. The phenotypic and clinical observations in the three subjects of this report are compared with previously reported findings.

Proximal extra material in the long arm of chromosome 15, has been described in individuals with different phenotypes (isolated mental retardation, multiple malformations, repeated miscarriages), and with apparently normal phenotype, in which cytogenetic analysis was invariably carried out on the basis of clinical indications. The paper describes a child with mental retardation, and his father, who both had proximal extra material in 15q. Caution is advised in the study of karyotype-phenotype correlation.

A family with popliteal pterygium syndrome is reported: two children presented a mild form of the syndrome, while their mother exhibited full expression of the gene. Only 11 families with 29 affected members and 25 sporadic cases have been published. This malformation syndrome is inherited in an autosomal dominant pattern, but environmental factors or genetic heterogeneity cannot be excluded in sporadic occurrences. The variability of expression is discussed and a comparison with previously published familial cases is made: minor anomalies, if present in relatives of patients with full gene expressions, are as helpful in making the diagnosis as are major abnormalities. Careful evaluation of the proband's family is essential for diagnosis and subsequent genetic counselling.

If a ring 21, originating from breaks close to the telomere of 21q and anywhere in 21p, replaces a normal 21, it may be associated with an apparently normal phenotype. An apparently normal mother and son were ascertained by a prenatal chromosome study. A second mother, with a ring 21 but without gross anomalies, is short of stature, has epilepsy and has a low normal intelligence. He daughter is a mosaic: 46,XX/47,XX,+r(21) and has the Down's syndrome. None of these four persons was found to have mitoses with more than one ring 21 or with rings of double size.

Pericentric inversion of chromosome 2 was detected in four unrelated families. All these inversions involved the segment p11 leads to q13. The pedigree data are considered in comparison with other cases reported in the literature. Segregation data and possible reproductive failures are discussed.

The enzymatic activity of G3PD and LDH-B in erythrocytes has been assayed in three patients carrying a rearrangement of the short arm of chromosome 12. The first patient is trisomic for the whole short arm. The second is trisomic only for the distal part and the third is monosomic for the proximal part. G3PD: Activity increased in patients 1 and 2 and normal in patient 3. LDH-B: Activity increased in patients 1 and 2 and decreased in patient 3. From these observations it is concluded that the erythrocytic G3PD locus is localized on the distal part of 12p, between 12p12.2 and 12 pter, and that LDH-B locus is on the middle third between 12p12.1 and 12p12.2

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.