Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects.

We evaluated a 11-year-old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work-up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.

[The significance of screening tests for aneuploidies in populations at low and high maternal-age-related risk]. / Il significato dei test di screening per le aneuploidie in popolazione a basso e alto rischio per età.

AIM: The aim of this study was to evaluate the validity of the triple test and the screen test in maternal populations at low and high maternal-age-related risk for fetal aneuploidy. METHODS: As a whole, 9,680 pregnant women at low risk and 627 at high risk underwent the triple test; 2,780 pregnant women at low risk and 408 at high risk underwent the screen or combined test; sensitivity, specificity, false positives and detection rate were compared between populations using Student's t-test. RESULTS: The triple test showed a detection rate of 75% in the low and 83.3% in the high risk population with a difference (P<0.003) for detection of trisomies 21 and 18 between the 2 populations; the screen test had a detection rates of 100% and 90% in the 2 populations, respectively, with a difference (P<0.005) between the 2 tests. CONCLUSIONS: Both tests are reliable for screening aneuploidies in the low risk population, the screen test having better performance; in the high risk population, the number of invasive procedures can be reduced by 78% with the triple test and by 84% with the screen test.

Chromosome 18 aberrations and epilepsy: a review.

Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17-18) (cen-q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re-evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo-insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo-insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.

A report of early (13 + 0 to 14 + 6 weeks) and mid-trimester amniocenteses: 10 years' experience.

OBJECTIVE: To report in singleton pregnancies the post-procedure safety and maternal complications of early amniocenteses performed between 13 + 0 and 14 + 6 weeks of gestation and mid-trimester amniocenteses performed between 15 + 0 and 18 + 6 weeks of gestation. METHODS: The study was carried out at the Prenatal Diagnosis Center, Siena University, Italy, during a 10-year period, following the Regional Protocol for Prenatal Diagnosis. Our study population included 3769 amniocenteses, 475 early and 3294 mid-trimester. Complications considered included miscarriage (immediately after the procedure and until 24 weeks of gestation), blood-stained amniotic fluid, failed cell culture, amniotic fluid leakage, preterm premature rupture of the membranes (PROM), preterm delivery and presence of neonatal talipes equinovarous. RESULTS: Cytogenetic anomalies were found in 111 cases (2.9%), 18 occurring early and the other 93 in mid-trimester. Miscarriage occurred in two cases in the early amniocentesis group (0.4%) and in ten cases among the mid-trimester group (0.3%). The overall loss of pregnancies due to amniocentesis in this study was 0.3%. Amniotic fluid was stained in 1.2% in the early group and 0.9% in the mid-trimester group. Amniotic fluid leakage was noted in 1.4% and 1.2%, preterm PROM was noted in 3.3%) and 3%, and preterm delivery occurred in 8% and 7.6%, respectively. There were no cases of failed amniotic culture and no cases of talipes equinovarous documented. CONCLUSIONS: The risks of early amniocentesis performed between 13 + 0 and 14 + 6 weeks appear to be comparable to those of mid-trimester amniocentesis and thus early amniocentesis could be offered to the parents, as an alternative to chorionic villus sampling, in order to obtain cytogenetic results earlier in pregnancy without a significantly increased risk for both mother and fetus. Further operators' experience with the method, based on long and accurate follow-up, and further studies are necessary to assess the safety of the method.

11q- and constitutional X trisomy in a patient with M5b acute non-lymphocytic leukemia.

A patient with M5b acute nonlymphoblastic leukemia (ANLL) and a 47,XXX del(11) (q23) karyotype is described. Partial remission was obtained after treatment with daunorubicin, arabinosylcytosine and VP-16. Subsequently, two courses of chemotherapy for resistant ANLL were administered without achieving complete remission. Abnormalities of chromosome 11 are typical of M4 and M5 ANLL. X trisomy is one of the most common human aneuploidia; however, correlation with increased incidence of hematological neoplasia has not been described.

[Correlations between karyotype and phenotype in structural and numerical abnormalities of chromosome 18]. / Correlazioni tra cariotipo e fenotipo nelle anomalie strutturali e numeriche del cromosoma 18.

Five cases with different abnormalities of chromosome 18 are described: one case with trisomy 18, two cases with ring 18, one case with partial trisomy 18q and one case with a mosaic 18p-/iso 18q. The karyotypes of the parents were normal. Cytogenetic analysis was performed on PHA stimulated blood lymphocytes. GTG, QFQ, MTX banding techniques were used. Karyotype-phenotype correlations are made. All patients present mental retardation, hypotonia and facial dismorphisms. The different degree of mental retardation and the clinical signs are in relation to the different size of deletions or trisomies of the short or long arm of chromosome 18. In the case with mosaicism 18p-/iso18q the phenotype is determined from the chromosomal abnormality more frequent in the cells (18p-).

[Correlation of the clinical phenotype with a pericentric inversion of chromosome 9]. / Correlazioni fra fenotipo clinico ed inversioni pericentriche del cromosoma 9.

Pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal aberrations. It is considered as a paraphysiological variant of a normal karyotype and it is possible to find it as occasional report in healthy subjects. In the last ten years different signals have appeared in literature, concerning carriers of pericentric inversion of chromosome 9, who showed different anomalies of the clinical condition. Today it is difficult, because of the rarity of the data to establish if a true correlation exists between phenotypical anomalies in the subjects studied and the pericentric inversion, or if they are only casual associations. We are trying to find possible correlations between the chromosomal rearrangements and eventual congenital defects. We describe 11 subjects with pericentric inversion of chromosome 9 examined for the presence of dysmorphic signs, mental retardation and repeated miscarriage.

[Familial segregation of simple and complex chromosomal rearrangements]. / Segregazione familiare di riarrangiamenti cromosomici semplici e complessi.

We report our observations about familial segregations of chromosomal aberrations: the simple forms and complex rearrangements. Congenital malformations and mental retardation, can be present both in unbalanced and in balanced translocations. Various hypotheses have been proposed to explain this phenomenon: in particular a possible "position effect" or genic mutation or genomic imprinting. In our study we have used both standard techniques and techniques with high resolution banding to investigate if the rearrangements were balanced or not. Molecular study and gene dosage have been used when possible, to define the correlation with the clinic phenotype.

[Serum T3, T4, FT3, TSH and TBG in Turner's syndrome]. / T3, T4, FT3, TSH e TBG sieriche nella sindrome di Turner.

Turner's syndrome was originally reported as sexual infantilism, short stature, webbed neck and cubitus valgus. Subsequent investigations, however, have disclosed many other abnormalities both in chromosomal and physical features occurring in this syndrome. An increased prevalence of Hashimoto's thyroiditis in patients with Turner's syndrome has been well documented and molecular defects of the TBG have been described. In our study we examined serum T3, T4, FT3, FT4, TSH and TBG levels in 18 girls with Turner's syndrome, in 18 healthy control girls and in the parents of both groups. We reported significant elevated levels of T3 and FT3 in the Turner's group (P 0.01). We did not find any quantitative abnormalities of immunoreactive TBG in the same patients.

[Correlations between individual and familial variables in Turner's syndrome]. / Correlazione tra variabili individuali e familiari nella sindrome di Turner.

In 20 cases of Turner's syndrome (10 with complete X monosomy, 10 with partial X monosomy or mosaicism) aged 3.47 to 15.5 years, the stature of the individual cases and their parents were evaluated. A significant frequency of short stature in mothers (25% below--2.0 S.D.S) has been observed, with a significant difference compared to the mean female stature of the general population. No significant difference has been observed on the stature of fathers. There was a closer correlation with mother's height (r = 0.65, p = 0.001) than with father's height (p = 0.07).

Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder.

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter.

A dominantly inherited syndrome (microcephaly, short stature, peculiar facies, mental retardation) associated with two balanced rearrangements involving chromosomes 2;7 and 5;20.

A complex balanced three-break-point rearrangement between chromosome 2 and chromosome 7 and a balanced reciprocal translocation between chromosome 5 and chromosome 20, were found associated in a girl and in her mother and grandmother. All three of them have microcephaly, low stature, peculiar asymmetric facies and slight mental retardation. We postulate that one (or more) of the five chromosome break-points disrupted one (or more) gene, leading to the expression of the syndrome and to its segregation with the chromosome rearrangement in three generation. Our finding confirms the efficiency of balanced translocations for gene mapping, althought it has led only to the exclusion mapping of all chromosomes except 2, 5, 7 and 20.

[Multiple pterygium syndrome]. / La sindrome degli pterigi multipli.

The authors relate about a non sporadic case of "Multiple pterygium syndrome" in a child born to consanguineous parents. Clinical features of the syndrome are: short stature, articular contractures, pterygia of the neck, axillae, elbows, facial anomalies, vertebral malformation, mental retardation. The syndrome, delineated as a distinct entity by Escobar, is a rare autosomal recessive disorder with a clinical heterogeneity, which is included within the "Arthrogryposis syndromes".

[Wolf-Hirschhorn syndrome]. / La sindrome di Wolf-Hirschhorn.

We refer about two children with Wolf-Hirschhorn's syndrome or syndrome with partial deletion of short arm of chromosome number 4. The diagnosis was possible with an accurate estimation of phenotype. Cytogenetics examination showed the chromosomal aberration typical for this syndrome.