Several patients with partial trisomy 6p resulting from parental balanced translocations or from a de novo duplication or insertion have already been described. Here, we report on the first case of familial pure trisomy 6p as a result of interstitial tandem duplication. The patient, an 11-year-old female, presented with mild dysmorphic features, moderate intellectual disability with behavioral disturbances, immunodeficiency, and epilepsy. Conventional cytogenetic analysis showed a duplication of the 6p region in the patient and in her mother presenting with a partially overlapping phenotype. The rearrangement was confirmed and defined by molecular cytogenetic analysis, including FISH and array CGH analysis showing a gain of ~13.8 Mb from 6p12.3 to 6p21.31. The phenotype of a pure partial trisomy 6p is extremely heterogeneous depending on the gene contents of the duplicated region. The clinical features of our patients have been compared with overlapping cases from the literature.

Partial trisomy of the long arm of chromosome 1 is a relatively rare cytogenetic anomaly. Its phenotype has still not been completely defined, because of the cytogenetic heterogeneity of the cases so far described. We report a prenatal case of partial 1q trisomy associated with partial monosomy 4q, secondary to balanced maternal translocation t(1;4). The trisomic segment extended from 1q31.1 to qter and the monosomy 4q was from 4q35.2 to qter. The phenotypic anomalies found by post-mortem and autopsy examinations were compared with those of similar cases reported in the literature. We performed standard cytogenetics and fluorescence in situ hybridization. Cerebral ventriculomegaly, present in our case, seemed to be a constant feature in partial 1q trisomies, so this cerebral malformation could be considered as the main echographic marker for this chromosomal imbalance and trisomy 1q should be added to the list of chromosomal abnormalities associated with ventriculomegaly.

Pallister-Killian syndrome (PKS) is a rare genetic disorder which is cytogenetically characterized by a tissue limited mosaic distribution of isochromosome 12p (tetrasomy 12p). This chromosomal anomaly may be detected in fibroblasts and in bone marrow cells, in amniocytes, chorionic villus and other foetal tissues, whereas it is absent in peripheral lymphocytes. The percentage of abnormal cells in fibroblasts decreases with the ageing, so adult patients may be undiagnosed.We report on a preterm male neonate of 1320 gr of weight, born at a gestational age of 29-30 weeks. He had severe respiratory distress and died after a few hours, in spite of intensive resuscitation. The external examination showed a disproportionate large face and low-set ears, limbs of normal length, with normal hands and feet, normal genitalia. At the autopsic examination all the thoracic, abdominal and pelvic organs were normal, the palate showed a schisis in the posterior side of the arch; the external appearance of the brain was normal, with hyperaemic pial membrane. The cytogenetic analysis on skin fibroblasts showed the presence of a supernumerary metacentric chromosome, consistent with an isochromosome 12p. Subsequent interphasic FISH with a centromeric probe detected tetrasomy 12p in mosaic.The postnatal phenotype of PKS is quite severe and include coarse facies with a high forehead, sparce scalp hair, hypertelorism, broad nasal bridge, hypotonia, streaks of hypo-hyperpigmentation. Hydramnios, congenital diaphragmatic hernia and micromelia, of predominantly rhizomelic type are frequent echographic signs during the pregnancy. Hydrops fetalis, hygroma colli, increased nuchal translucency (INT), foetal overgrowth and ventriculomegaly are less frequently reported. In the present case no foetal malformations were evident during the pregnancy, and the facial dysmorphisms and congenital malformations described in PKS were absent at the morphological and autopsic examination of the newborn. This suggests that PKS could be suspected, and then verified on skin fibroblasts, even in absence of significant congenital malformations, mainly in dysmorphic patients cytogenetically normal at standard cytogenetics on peripheral lymphocytes.

Monosomy for the short arm of chromosome 18 is one of the most common autosomal deletion syndromes, with an estimated incidence of about 1:50000 live-born. The phenotype of this chromosome imbalance is greatly variable, often not evident at birth. In this communication we describe a case prenatally diagnosed of de novo 18p deletion.Amniocentesis was performed at 17 weeks of gestational age on a 39-year-old gravid. The family history was unremarkable and the pregnancy was uncomplicated. At the time of the amniocentesis the amniotic fluid alphafetoprotein level was slightly lower than normal. The pregnancy was terminated at 18 weeks, after the cytogenetic response. At the time the ultrasonographic examination showed reduced biparietal diameter and head circumference, normal limbs, normal thoracic, abdominal and pelvic organs. The external examination of the aborted foetus showed: weight 380 gr; ipsicephaly and nuchal oedema, no facial dysmorphic signs, normal ears, limbs of normal length, overlapping toes in the right foot. External genitalia were normal. At the autopsic examination the right lung showed four lobes; all the other organs of thorax, abdomen and pelvis were normal.Cytogenetic analysis of cultured amniocytes showed a de novo 18p deletion. FISH studies allowed us to define the foetal karyotype as: 46,XX, del(18)(p10pter).ish del(18)(tel18p-, dim D18Z1). The phenotypic spectrum of 18p- syndrome may include: round face, ptosis, flat and broad nasal bridge, wide mouth with short upper lip, small mandibles, irregular teeth and dental caries, large, protruding ears, often low and posteriorly rotated, short neck, pectus excavatum, kyphoscoliosis, hands and feet anomalies. The main malformations are holoprosencephaly (HPE), cardiac defects and genital anomalies. Growth retardation, psychomotor delay and mental insufficiency, often mild, are constant symptoms of the syndrome. The foetal phenotype is inconsistent, but the increased nuchal translucency (INT) seems to be a sonographic sign suggestive of this chromosomal abnormality. This further stress the importance of accurate morphological ultrasonographies, mainly in the second trimester, in order to prevent rare and oligosymptomatic chromosomal syndromes.

We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth, one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13. A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported.

We describe two malformed infants with trisomy 6p12.1-p22.1 due to 12/6 interchromosomal insertion. The phenotypic data observed in these patients are compared chiefly with a case cytogenetically similar described by Villa et al. [A. Villa, E.G. Gomez, L. Rodriguez, R.H. Rastrollo, M.E. Martinez Tallo, M.L. Martinez-Frias, Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3), Am. J. Med. Genet. 90 (2000) 369-375]. All three infants are trisomic for a genomic segment which largely overlaps that reported as duplicated in previous cases, but with the addition of a more proximal segment, extending from 6p12 to 6p21. We suggest that some of their phenotypic anomalies are due to the trisomy of this chromosomal region. We also speculate on the possible role played by the TFAP2B (Transcription Factor AP2-beta) gene, which is one of the genes mapped on the duplicated segment.

We report the results of a molecular study of a large family segregating the complete form of the Androgen Insensitivity Syndrome (CAIS) in several members from three generations. We identified the mutant allele by Polymerase Chain Reaction (PCR) amplification of the short tandem repeat (CAG)n, highly polymorphic in the population, present in the first exon of the androgen receptor (AR) gene. In this family four different alleles were detected and one of these showed a perfect segregation with the disease. This study enabled us to identify the heterozygous females in this family. We think that this simple, indirect test, is also suitable for prenatal diagnosis of Morris' syndrome when the mother is heterozygous for the size of the short tandem repeat and one affected subject in the family may be studied.

In situ hybridization of a telomeric (TTA-GGG)n sequence to metaphases from three cases of ring chromosome, involving respectively chromosomes 4, 16, and 20, showed the presence of the cognate sequences in all three rings. To investigate whether these ring chromosomes originated by telomere-telomere fusion, we determined, by in situ hybridization, whether telomere-associated sequences and/or specific distal sequences were still present in the ring chromosomes. The finding that these sequences were preserved in all the ring chromosomes strongly indicates that they originated by telomere-telomere fusion. All three subjects carrying the ring chromosomes are affected by the so-called ring syndrome, with failure to thrive, minor dysmorphic signs and no major anomalies. The r(4) patient has the ring in mosaic form with a normal cell line and has normal intelligence. The r(16) and the r(20) patients have moderate mental retardation and suffer from seizures. We conclude that the ring syndrome, even in its more severe manifestation, is caused by ring chromosome instability.