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Neste trabalho foi avaliada a influência do tratamento de fibras de bagaço de cana-de-açúcar nas propriedades mecânicas e dinâmico-mecânicas, na estabilidade térmica, na densidade e absorção de água, quando utilizadas na preparação de compósitos com resinas de poliéster insaturado em comparação com a resina sem reforço. As fibras foram submetidas a tratamento químico com solução alcalina de hidróxido de sódio. O tratamento melhorou as propriedades de impacto, aumentou o módulo de elasticidade em flexão, não alterou significativamente o módulo de elasticidade em tração dos compósitos em relação à resina sem reforço e melhorou a compatibilidade fibra matriz quando comparada com compósitos com a fibra sem tratamento, o que pode ser observado nas fraturas de impacto analisadas por microscopia eletrônica de varredura. As superfícies das fibras também foram avaliadas por microscopia eletrônica de varredura.The aim of this work is to evaluate the influence of the sugar cane bagasse NaOH treatment in the mechanical and dynamic-mechanical properties, in the thermal stability, density and water absorption, when used in unsaturated polyester resin/sugar cane bagasse composite. The sugar cane bagasse was submitted to the chemical treatment with alkaline solution of NaOH. The treatment improves the impact and flexural elasticity modulus when compared with resin without fibers, in addition to the adhesion of the fibers with the matrices, but does not improve significantly the tensile elasticity modulus. The surfaces of the impact fracture were analyzed by SEM.

Here we describe a foetus with intrauterine growth retardation (IUGR), cerebral malformations and a 46,XY,der(1),t(1;6)(p36.3;q25.2) karyotype owing to a familial cryptic translocation segregating in three generations. A balanced translocation was present in the mother, the maternal uncle, the aunt and the grandmother. A female first cousin with dysmorphisms, hydrocephalus and mental retardation was a carrier of a partial trisomy 1p and a partial monosomy 6q. Multiple miscarriages were present in the family pedigree. Parents of the foetus had three other pregnancies: a male with a balanced translocation, and two foetuses with 1p36.3–pter monosomy and 6q25.2–qter trisomy. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories., Methods: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed., Results: Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound., Conclusions: NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling., (© 2022 John Wiley & Sons Ltd.)

Our objective is to collect data and information for a better care and follow up in Cri du Chat patients. We conducted a literature review in August 2017 and then discuss the outcomes within the ABC (Associazione Bambini Cri du Chat, Italian CdC families support group). A proposal for clinical, laboratory and imaging work up should be performed at various ages in CdC patients. Follow up and rehabilitation should continue lifelong as some improvements can be obtained also in older ages and not to lose acquired skills., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Metformin (MET) is the drug of choice for patients with type 2 diabetes and has been proposed for use in cancer therapy and for treating other metabolic diseases. More than 14,000 studies have been published addressing the cellular mechanisms affected by MET. However, several in vitro studies have used concentrations of the drug 10-100-fold higher than the plasmatic concentration measured in patients. Here, we evaluated the biochemical, metabolic, and morphologic effects of various concentrations of MET. Moreover, we tested the effect of MET on Fanconi Anemia (FA) cells, a DNA repair genetic disease with defects in energetic and glucose metabolism, as well as on human promyelocytic leukemia (HL60) cell lines. We found that the response of wild-type cells to MET is concentration dependent. Low concentrations (15 and 150 µM) increase both oxidative phosphorylation and the oxidative stress response, acting on the AMPK/Sirt1 pathway, while the high concentration (1.5 mM) inhibits the respiratory chain, alters cell morphology, becoming toxic to the cells. In FA cells, MET was unable to correct the energetic/respiratory defect and did not improve the response to oxidative stress and DNA damage. By contrast, HL60 cells appear sensitive also at 150 μM. Our findings underline the importance of the MET concentration in evaluating the effect of this drug on cell metabolism and demonstrate that data obtained from in vitro experiments, that have used high concentrations of MET, cannot be readily translated into improving our understanding of the cellular effects of metformin when used in the clinical setting., (© 2017 Wiley Periodicals, Inc.)

Background: Recurrent reciprocal 1q21.1 deletions and duplications have been associated with variable phenotypes. Phenotypic features described in association with 1q21.1 microdeletions include developmental delay, craniofacial dysmorphism and congenital anomalies. The 1q21.1 reciprocal duplication has been associated with macrocephaly or relative macrocephaly, frontal bossing, hypertelorism, developmental delay, intellectual disability and autism spectrum disorder., Methods: Our study describes seven patients, who were referred to us for developmental delay/intellectual disability, dysmorphic features and, in some cases, congenital anomalies, in whom we identified 1q21.1 CNVs by array-CGH., Results: Our data confirm the extreme phenotypic variability associated with 1q21.1 microdeletion and microduplication. We observed common phenotypic features, described in previous studies, but we also described, for the first time, congenital hypothyroidism in association with 1q21.1 deletion and trigonocephaly associated with 1q21.1 duplication., Conclusions: The aim of this study is to contribute to the definition of the phenotype associated with reciprocal 1q21.1 deletions and duplications.

Brachydactyly type E is a congenital limb malformation characterized by small hands and feet as a result of shortened metacarpals and metatarsals. Genetic causes of this anomaly are heterogeneous and only partially characterized. In this report we describe an Italian family in which four subjects share brachydactyly type E and a 3 Mb microduplication in region 6p25. The duplication involves the gene FOXC1, expressed during the osteoblast differentiation, which appears a potential candidate gene for brachydactyly., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We report a case of a 13-year-old girl with a 5.4 Mb de novo deletion, encompassing bands 2q23.3q24.1, identified by array-comparative genomic hybridization. She presented with minor facial and digital anomalies, mild developmental delay during infancy, and behavioral disorders. Few of the reported cases overlap this deletion and all only partially. We tried to compare the clinical features of the patient with the other cases, even though not all of them were molecularly characterized in detail. Considering the neuropsychiatric involvement of the proband and the clinical descriptions of other similar cases, we attempted to identify the genes more probably involved in neurological development and function in the deleted region, particularly GALNT13, KCNJ3 and NR4A2, which are expressed in neuronal cells., (© 2014 Japanese Teratology Society.)

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes., (Copyright© Ferrata Storti Foundation.)

It is estimated that 10-15 % of all clinically recognised pregnancies results in a miscarriage, most of which occur during the first trimester. Large-scale chromosomal abnormalities have been found in up to 50 % of first-trimester spontaneous abortions and, for several decades, standard cytogenetic analysis has been used for their identification. Recent studies have proven that array comparative genomic hybridisation (array-CGH) is a useful tool for the detection of genome imbalances in miscarriages, showing a higher resolution, a significantly higher detection rate and overcoming problems of culture failures, maternal contamination and poor chromosome morphology. In this study, we investigated the possibility that submicroscopic chromosomal changes, not detectable by conventional cytogenetic analysis, exist in euploid miscarriages and could be causative for the spontaneous abortion. We analysed with array-CGH technology 40 foetal tissue samples derived by first-trimester miscarriages with a normal karyotype. A whole-genome microarray with a 100-Kb resolution was used for the analysis. Forty-five copy number variants (CNVs), ranging in size between 120 Kb and 4.3 Mb, were identified in 31 samples (24 gains and 21 losses). Ten samples (10/31, 32 %) have more than one CNV. Thirty-one CNVs (68 %) were defined as common CNVs and 14 were classified as unique. Six genes and five microRNAs contained within these CNVs will be discussed. This study shows that array-CGH is useful for detecting submicroscopic CNVs and identifying candidate genes which could account for euploid miscarriages.

Complex chromosomal rearrangements (CCRs) are structural aberrations involving more than two chromosomes with at least three breakpoints. CCRs can be divided into familial and de novo. Balanced CCR are extremely rare in humans and are at high risk of producing unbalanced gametes. Individuals with balanced CCR are usually phenotipically normal but report fertility problems, recurrent miscarriages or congenital anomalies in newborn offsprings as consequence of either meiotic failure or imbalanced chromosomes segregation.We describe the case of an unbalanced CCR involving chromosomes 1, 4 and 8 found in a girl with developmental delay, hexadactilia and microcephaly. The rearrangement, apparently balanced at a standard karyotype analysis and of maternal origin, was demonstrated to be unbalanced by array-CGH and FISH. In conclusion our study underlines the importance of the combined use of a quantitative technique, as array-CGH, to detect criptic segmental aneuploidies, and a qualitative tool, as FISH analysis, to physically map the localization of the chromosome segments involved, in order to realize the exact nature that underlies a chromosomal rearrangement.

Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at least 10 cases involving this region have been described and all patients showed a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated with intellectual disability (ID), bilateral microphthalmia, and coloboma, without cerebral anomalies typical of HPE. Except for ocular defects (i.e., microphthalmia, coloboma) consistent with HPE-type anomalies, the minor facial dysmorphia was not suggestive for HPE and the absence of cerebral anomalies should rule out this diagnosis. The deletion of the potential HPE candidate genes NPAS3, EAPP, SNX6, and TULIP1, raises doubts about their pathologic role in determining HPE. It is likely that deletions of HPE genes are not sufficient to cause HPE, and that multiple genetic, chromosomal, and environmental factors interact to determine the variable clinical expression of HPE. This is the first case of a 14q deletion encompassing the HPE8 locus with the only features consistent with HPE-type anomalies affecting the ocular system (i.e., microphthalmia, coloboma), and without cerebral anomalies specific for HPE. The inclusion of potential HPE candidate genes in the deletion raises the question whether this patient is affected by a less severe form of HPE (HPE microform), or whether he has a new ID/MCA deletion syndrome., (Copyright © 2012 Wiley Periodicals, Inc.)

Unlabelled: We report two individuals with developmental delay and dysmorphic features, in whom array-based comparative genomic hybridization (array CGH) led to the identification of a 2p15p16.1 de novo deletion. In the first patient (Patient 1) a familial deletion of 6q12, inherited from her father, was also detected. In the second patient (Patient 2) in addition to the 2p15p16.1 microdeletion a de novo deletion in Xq28 was detected. Both individuals shared dysmorphic features and developmental delay with the six reported patients with a 2p15p16.1 microdeletion described in medical literature., Conclusion: in the first patient a 642 kb 2p16.1 deletion (from 60.604 to 61.246 Mb), and a 930 kb 6q12 familial deletion, was detected and in the second a 2.5 Mb 2p15p16.1 deletion (from 60.258 to 62.763 Mb), with a Xq28 deletion, was discovered. The common dysmorphic features and neurodevelopmental delay found in these patients are in agreement with the clinical phenotype of a microdeletion syndrome involving 2p15p16.1. Our data confirm the hypothesis suggesting that 2p15p16.1 deletion is a contiguous gene syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy., Design: Prospective cohort study., Setting: Epilepsy centers in Italy., Patients: Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization., Main Outcome Measures: Identification of copy number variations (CNVs) and gene enrichment., Results: Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy., Conclusions: Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.

Subtelomeric terminal 6p deletion has been recognized as a clinically identifiable syndrome including facial dysmorphism, malformation of the anterior eye chamber, hearing loss, heart defects, and developmental delay. Genotype-phenotype correlations of previously published patients have strongly suggested anterior eye segment anomalies as one of the major malformations of the syndrome if the critical 6p25 region contains the FOXC 1 gene. In addition, the presence in this region of one or more genes involved in hearing loss has been hypothesized. We report a patient with a 47,XYY karyotype and submicroscopic terminal 6p deletion. Further characterization of the deletion with array comparative genome hybridization also revealed a cryptic microduplication on chromosome 19. The patient showed dysmorphic features, neuromotor retardation, and profound language impairment, in absence of hearing loss and structural eye anomalies. As far as we know this is the first reported terminal 6p25.1 deletion case without eye dysgenesis precisely characterized by array-CGH. Our result suggests that the genes in this region may not be obvious candidates for hearing loss and demonstrate the need for further elucidation of the function of the genes involved in eye developmental processes., (Copyright © 2011 Wiley Periodicals, Inc.)

Chromosome 22, particularly the q11.2 sub-band, has long been recognized as responsible for multiple congenital anomaly disorders. In particular, its susceptibility to subtle microdeletions or, more rarely, microduplications has been attributed to the presence of several low-copy repeats spanning the region as mediators of nonallelic homologous recombination that result in 22q11.2 rearrangements. While recent data suggest that the frequency of 22q11.2 microduplications could be approximately half of all deletions, now only 50 unrelated cases have been reported thus far. However, it is reasonable to suppose that microduplications of 22q11.2 may be largely undetected as a result of a less-distinct, unpredictable, and/or milder phenotype ranging from normal to mild learning difficulties with/without other multiple defects. We report on the first case of myoclonic epilepsy in a 10-year-old boy carrying a de novo 22q11.2 microduplication. Emphasizing that this rare association could be one of the many unrecognized aspects underlying this new emerging syndrome and once again its clinical heterogeneity, we suggest further investigation of the function of the RAB36 gene and propose that in the screening of individuals with developmental delay, minor behavioral problems mild dysmorphology and seizures, investigation of 22q11.2 microduplications should be considered., (Copyright © 2011 Wiley Periodicals, Inc.)

The interstitial duplication of the long arm of chromosome 19 is a rare abnormality, characterized by developmental delay and dysmorphic features, also reported in association with cardiac, urinary, and CNS malformations. We describe a new case of de novo 19q12-q13.2 duplication characterized by fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (CGH) and, by reviewing the data from previous articles, we report a tentative genotype/phenotype correlation. Four previously described cases showed the same or overlapping 19q duplications and shared with our patient common dysmorphisms, psychomotor retardation, and CNS malformations. The present description of a new case of 19q12-q13.2 duplication with a molecular cytogenetic and genomic characterization adds further elements to the understanding of the impact of the genomic segment on the phenotype.

Mental retardation, facial dysmorphisms, seizures, and brain abnormalities are features of 6q terminal deletions. We have ascertained five patients with 6q subtelomere deletions (four de novo, one as a result of an unbalanced translocation) and determined the size of the deletion ranging from 3 to 13 Mb. Our patients showed a recognizable phenotype including mental retardation, characteristic facial appearance, and a distinctive clinico-neuroradiological picture. Focal epilepsy with consistent electroencephalographic features and with certain brain anomalies on neuroimaging studies should suggest 6q terminal deletion. The awareness of the distinctive clinical picture will help in the diagnosis of this chromosomal abnormality.

A computer model of pressure response to hemodialysis-induced hypovolemia is reported. Heart rate and hematocrit, measured in the course of hemodialysis, are imposed as computer model inputs and the model computes the arterial pressure response after tuning model parameters representative of patient's cardiovascular reactivity. Computer model reproduced with good accuracy experimental data (arterial pressure, cardiac output and total peripherical resistance). Parameter identification over successive sessions of the same patients revealed satisfactory reliability, providing a physiological interpretative key to patient's hemodynamic behavior during hemodialysis.

Purpose: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype., Methods: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses., Results: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15., Conclusion: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling.

Sotos syndrome is characterized by pre- and post-natal overgrowth, typical craniofacial features, advanced bone age, and developmental delay. Some degree of phenotypic overlap exists with other overgrowth syndromes, in particular with Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving the gene are the major cause of the syndrome in Japanese patients, whereas intragenic mutations are more frequent in non-Japanese patients. NSD1 aberrations have also been described in some patients diagnosed as Weaver syndrome. Some authors have suggested a certain degree of genotype-phenotype correlation, with a milder degree of overgrowth, a more severe mental retardation, and a higher frequency of congenital anomalies in microdeleted patients. Data on larger series are needed to confirm this suggestion. We report here on microdeletion and mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen novel mutations, two previously described and one microdeletion were identified. All patients with a NSD1 mutation had been clinically classified as "classical Sotos," although their phenotype analysis demonstrated that some major criteria, such as overgrowth and macrocephaly, could be absent. All patients with confirmed mutations shared the typical Sotos facial gestalt. A high frequency of congenital heart defects was present in patients with intragenic mutations, supporting the relevance of the NSD1 gene in the pathogenesis of this particular defect.

Objectives: The risk of uniparental disomy (UPD) occurrence associated with the prenatal finding of balanced nonhomologous Robertsonian translocations (NHRTs) has been estimated only on limited empirical data. The aim of the study was to verify the estimate of the general risk, to get narrower confidence intervals by cumulating the data and to obtain risk estimates for specific translocation types., Methods: We tested for UPD 160 prenatal specimens referred to the participant centers after the cytogenetic finding of NHRT., Results: One case of upd(14)mat was found, associated with a 45,XX,der(14;22)mat fetal karyotype. The general empirical risk of UPD occurrence in NHRT carrier fetuses, corrected for the actual number of chromosomes analyzed, was 0.76% (95% CI 0.02-4.25%). Cumulative data with previous studies gives a general risk of UPD associated with NHRT of 0.80% (95% CI 0.17-2.34%). The UPD risk for the specific NHRT der(13;14) did not significantly differ from that of the other NHRTs taken together., Conclusion: The present survey confirms the previously estimated risk of occurrence of UPD in offspring of NHRT carriers as a low, but not negligible risk, worth being investigated in prenatal diagnosis., (Copyright 2004 John Wiley & Sons, Ltd.)

Here we describe a foetus with intrauterine growth retardation (IUGR), cerebral malformations and a 46,XY,der(1),t(1;6)(p36.3;q25.2) karyotype owing to a familial cryptic translocation segregating in three generations. A balanced translocation was present in the mother, the maternal uncle, the aunt and the grandmother. A female first cousin with dysmorphisms, hydrocephalus and mental retardation was a carrier of a partial trisomy 1p and a partial monosomy 6q. Multiple miscarriages were present in the family pedigree. Parents of the foetus had three other pregnancies: a male with a balanced translocation, and two foetuses with 1p36.3-pter monosomy and 6q25.2-qter trisomy., (Copyright 2003 John Wiley & Sons, Ltd.)

Transient myeloid disorder is a unique self-regressing neoplasia specific to Down's syndrome. The transcription factor GATA1 is needed for normal growth and maturation of erythroid cells and megakaryocytes. Mutations in GATA1 have been reported in acute megakaryoblastic leukaemia in Down's syndrome. We aimed to investigate changes in GATA1 in patients with Down's syndrome and either transient myeloid disorder (n=10) or acute megakaryoblastic leukaemia (n=6). We recorded mutations eliminating exon 2 from GATA1 in all patients with transient myeloid disorder (age 0-24 days) and in all with acute megakaryoblastic leukaemia (age 14-38 months). The range of mutations did not differ between patients with each disorder. Patients with transient myeloid disorder with mutations in GATA1 can regress spontaneously to complete remission, and mutations do not necessarily predict later acute megakaryoblastic leukaemia.

The 18q- syndrome [MIM #601808] is a terminal deletion of the long arm of chromosome 18. The most common deletion extends from region q21 to qter. We report here a nine-year-old boy possessing a simple 18q- deletion who had abnormalities of the brain, skull, face, tooth, hair, bone, and skin, plus joint laxity, tongue palsy, subtle sensoneural deafness, mental and speech delay, attention deficit hyperactivity disorder (ADHD), tic, and restless legs syndromes. His karyotype was 46, XY, del (18)(q21.31-qter). The size of the deletion was approximately 45 cM. Most of these abnormalities were not explained by the 18q- deletion. The family pedigree suggested the presence of a subtle involvement of ectodermal and/or mesodermal structures. Karyotypes of the other family members were normal., (Copyright 2002 Wiley-Liss, Inc.)