Autism spectrum disorder in Kabuki syndrome: clinical, diagnostic and rehabilitative aspects assessed through the presentation of three cases.

Kabuki syndrome (KS) (Kabuki make-up syndrome, Niikawa-Kuroki syndrome) is a rare genetic disorder first diagnosed in 1981. Kabuki make-up syndrome (KMS) is a multiple malformation/intellectual disability syndrome that was first described in Japan but is now reported in many other ethnic groups. KMS is characterized by multiple congenital abnormalities: craniofacial, skeletal, and dermatoglyphic abnormalities; intellectual disability; and short stature. Other findings may include: congenital heart defects, genitourinary anomalies, cleft lip and/or palate, gastrointestinal anomalies including anal atresia, ptosis and strabismus, and widely spaced teeth and hypodontia. The KS is associated with mutations in the MLL2 gene in some cases were also observed deletions of KDM6A. This study describes three children with autism spectrum disorders (ASDs) and KS and rehabilitative intervention that must be implemented.

Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma.

In order to evaluate the free radical defense systems of melanocytes and their possible correlation with melanoma, we have studied in cultured normal human melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma cells (40) the fatty acid pattern of membrane phospholipids as a target of peroxidative damage and the superoxide dismutase and catalase activities, vitamin E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in the same medium and analyzed at III or IV passage. Compared to the values obtained in normal human melanocytes, melanoma cells showed on average: a) higher levels of polyunsaturated fatty acids, b) increased superoxide dismutase and decreased catalase activities, higher vitamin E, and lower ubiquinone levels. Among the normal melanocytes from melanoma patients studied, two groups were differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants level similar to those of normal human melanocytes; b) cultures (8) with antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated fatty acids were also increased in the latter group. The results indicate that in melanoma cells and in a percentage of normal melanocytes from melanoma patients, an imbalance in the antioxidant system can be detected that can lead to endogenous generation of reactive oxygen species and to cellular incapability of coping with exogenous peroxidative attacks. These alterations could be correlated with the malignant transformation of cells and with the progression of the disease.

Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo.

To examine the sensitivity of vitiligo melanocytes to external oxidative stress, we studied enzymatic and non-enzymatic anti-oxidants in cultured melanocytes of normal subjects (n = 20) and melanocytes from apparently normal skin of vitiligo patients (n = 10). The activity of superoxide dismutase and catalase and the intracellular concentrations of vitamin E and ubiquinone were evaluated in cultures at the fourth or fifth passage. In addition, cells were exposed to various concentrations of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66-20 microM), for 1 and 24 h. Compared to normal melanocytes, vitiligo melanocytes showed normal superoxide dismutase and significantly lower catalase activities and higher vitamin E and lower ubiquinone levels. At the concentration used, CUH did not significantly affect cell number or viability of melanocytes after either period of culture. On the contrary, vitiligo melanocytes were susceptible to the toxic effect of CUH after 24 h of continuous treatment at concentrations greater than 6.6 microM. The degree of CUH toxicity correlated strictly with the anti-oxidant pattern, defined as the ratio between vitamin E concentration and catalase activity, suggesting that the alteration in the antioxidants was the basis for sensitivity to the external oxidative stress. Our results demonstrate the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes and provide further support for a free radical-mediated damage as an initial pathogenic event in melanocyte degeneration in vitiligo.

Antioxidant pattern in uveal melanocytes and melanoma cell cultures.

PURPOSE: To investigate the antioxidant status of cultured uveal melanocytes from patients with uveal melanoma and uveal melanoma cells to characterize some of the biochemical properties of these cells in respect to the normal cutaneous melanocytes. METHODS: The fatty acid pattern of membrane phospholipids, intracellular vitamin E level, and superoxide dismutase (SOD) and catalase activities were studied in uveal melanocytes (n = 10) and uveal melanoma cell (n = 10) cultures, by gas chromatography mass spectrometry or by spectrophotometer. RESULTS: Among the uveal melanocyte cultures, two groups were differentiated, according to catalase activity: group A with catalase values comparable to those of cutaneous ones and higher SOD activity and group B with catalase values 2 SD lower (P<0.001) and lower SOD activity. Vitamin E concentration was not significantly different between melanoma cells and melanocytes, whereas a significantly higher percentage of polyunsaturated fatty acids was found in melanoma cells and the B group of melanocytes (P = 0.022). In uveal melanoma cells SOD activity was significantly lower than that detected in uveal melanocytes (P< 0.005). CONCLUSIONS: These results show a different pattern of antioxidants in uveal melanocytes with respect to cutaneous ones, possibly related to the anatomic distribution. However, as in cutaneous melanocytes, two subgroups were identified on the basis of the antioxidant pattern that could be the expression of a constitutional increased susceptibility to oxidative stress in some subjects. Moreover, an imbalance of the antioxidants was observed in melanoma cells, possibly related to the disease status and progression.

3p13 region: a possible location of a tumor suppressor gene involved in uveal melanoma.

To contribute to a better understanding of the role of chromosomal rearrangements in the tumorigenesis of uveal melanoma, we present a case in which a structural aberration of chromosome 3 could indicate the specific region in which an uveal melanoma tumor suppressor gene could be located. We obtained a primary cell culture, characterized by cytogenetic study, through GTG- and CBG-banding techniques by using a mechanical dissection of a tumor sample obtained from an uveal melanoma. Cytogenetic analysis performed in the primary cell culture highlighted the presence of a structural rearrangement involving chromosomes 3 and 22. A t(3;22)(p13;p11) was observed as the only present clonal aberration. The 3p13 breakpoint involved in the aberration observed in our case could be essential in restricting the candidate region for the locus of an uveal melanoma tumor suppressor gene located on chromosome 3.

Cytogenetic findings in 20 melanomas.

We report cytogenetic studies performed on 20 patients with cutaneous malignant melanoma, characterized by clinical and histological parameters. Cytogenetic analyses were performed on peripheral blood lymphocytes, in order to exclude the presence of constitutional chromosomal aberrations, and on primary cell cultures obtained from neoplastic skin lesions. A metastasis was also cultured in order to characterize chromosome markers. Specific markers found in more than one patient were t(1;14)(q21;q32) and aberrations of the 4q21,8q24 and 10q24q26 regions. The research aims to identify possible subtypes of melanomas related to specific chromosomal markers. It is hoped that this will contribute to understanding of the aetiology and evolution of the disease in order to obtain a more exact classification. We compare our results with the data reported in the literature and discuss the possible role of the cytogenetic analyses in human malignant melanoma.

Detection of a 46,XX,der(3)t(3;4)(p25;p16.1) by using chromosome microdissection.

We performed chromosome microdissection in order to define the "de novo" rearrangement observed in a female patient affected by: frontal microgyria, mild psychomotor retardation, thoracic scoliosis, XIIth rib asymmetry and facial dysmorphisms. Through the use of the micro-FISH we evidenced a deletion of the 3p25pter region and a 4p16.1 duplication. We performed a karyotype-phenotype correlation in our patient and in the ones previously reported in literature which had a 3p25pter deletion or the 4p16 duplication.

2q35qter duplication syndrome: phenotypic definition.

Two sibs with multiple congenital anomalies and severe mental retardation were found to have a 2q35qter duplication as a result of a balanced maternal translocation. The clinical features of our two cases are compared with those reported in literature as having either a 2q35qter duplication or a wider duplicated segment without the involvement of any other chromosome deletion or duplication. The typical phenotype is described considering the characteristic clinical features as: hypotonia, hypertelorism, short and beaked nose, flat nasal bridge, thin upper lip, micrognathia, low set and dysmorphic ears, clinodactyly finger V and cryptorchidism.

Referential communication skills in children with Down Syndrome.

AIM: The aim of this study was to investigate referential communication skills in children with Down Syndrome (DS). We studied the development of pragmatic language in relation to nonverbal skills by analyzing referential communication skills in children with DS, in both production and comprehension of referential messages: oriented and/or ambiguous, adequate (appropriate) and inadequate (inappropriate). METHODS: The study population was 24 children: 12 with DS (mean age, 7.8 years) and 12 with normal development (control group) (mean age, 7.4 years). In the first phase (F1), all 24 children were administered a test to evaluate their nonverbal skills, followed in a second phase (F2) by a test to specifically evaluate their referential communication skills. RESULTS: A strong relationship between nonverbal and referential communication skills was found, in which the nonverbal skills contributed to variations in referential performance, especially among the children with DS. Furthermore, the children with DS showed better performance in the "talking" than the "listener" condition. Within the listener condition, a significant correlation emerged between adequate and inadequate messages. CONCLUSION: Referential communication skills are influenced by several verbal and nonverbal factors.

The quality of life in developing age children with celiac disease.

AIM: The moments that follow the diagnosis of celiac disease and the early stages of the gluten-free diet are extremely difficult and complex for parents and child, because they face an important change punctuated by self-denial and deprivation. The main objective of this research is to assess the impact of celiac disease on quality of life in subjects in developmental age, taking into account the perceptions of parents about the child's illness, with the aim to highlight the effect of disease on the child and the entire family. METHODS: The study included both parents of 45 children aged between 2 and 10 years, with established celiac disease. To evaluate the effect of celiac disease on the lifestyle of affected children and their families has been used, after having adapted to the Italian context, the Impact Scale of Childhood Diseases of Hoare and Russell (1995). This study shows that celiac disease is a condition that has a significant impact on both the child and his family. RESULTS AND CONCLUSION: The results obtained by administration of Impact Scale of Childhood Diseases to parents showed that subjects in developmental age with celiac disease could have difficulty on emotional level that affect child development and the whole family context. Acceptance of the illness by the child depends mainly by how much and how this has been accepted by parents.

Evaluation of creative thinking in children with idiopathic epilepsy (absence epilepsy).

AIM: Creativity represents the silent character of human behaviour. In children with epilepsy, cognitive performance of has mainly been investigated under the assumption that the disorder represents a risk factor for the development of intellectual function. In subjects with different forms of epilepsy, neuropsychologic disorders have been detected even when cognitive-global functioning is unimpaired. The cognitive functions of subjects with epilepsy have been widely studied, but their creativity has been never evaluated to date. The aim of this study was to describe the development of creative thinking in a group of children with absence epilepsy. METHODS: The test battery included: the Torrance Test of Creative Thinking (TTCT), the Wechsler Intelligence Scale for Children-revised (WISC-R) and the Goodenough Human Figure Drawing Test. RESULTS: Statistical analysis (Mann-Whitney test) showed a statistically significant difference (P <0.05) in test scores between two groups of subjects (children with epilesy vs control group), with higher scores for figure originality, figure fluidity and figure elaboration in the control group. There was a significant correlation (Spearman's rho) between verbal IQ and verbal fluidity and verbal flexibility subscale scores and between performance IQ and figure elaboration, between total IQ and verbal fluidity and verbal flexibility subscales (P <0.05; r >0.30). CONCLUSION: Low scores on the figure originality subscales seem to confirm the hypothesis that adverse psychodynamic and relational factors impoverish autonomy, flexibility and manipulator interests. The communication channels between subjects with epilepsy and their family members were affected by the disorder, as were the type of emotional dynamics and affective flux.

Hypomelanosis of Ito: neurological and psychiatric pictures in developmental age.

Hypomelanosis of Ito (HOI) is a multisystem neurocutaneous disorder. In the described cases, cutaneous manifestations (unilateral or bilateral streaks and swirls of hypomelanosis with regular and confluent borders) and extracutaneous abnormalities are often associated. Extracutaneous abnormalities involve the musculoskeletal system (scoliosis, vertebral anomalies, cranial-facial malformations) and other organs, as well as the central nervous system (CNS). The most significant anomalies of the CNS are psychomotor retardation and cognitive deficit. Autism, epilepsy, language disorders, cerebral malformations (neural migration disorders, cerebral hypoplasia, cortical atrophy, agenesis of the corpus callosum) are sometimes present. Numerous abnormal chromosomal patterns have been observed. HOI is usually a sporadic disorder; though autosomal dominant transmission has been suggested, recessive and X-linked inheritance patterns have also been reported. This study describes five children with HOI presenting with various features of the clinical spectrum of the syndrome. Some of these cases were referred for psychomotor therapy as part of an integrated neuropsychologic and psychomotor treatment support program. In this view, psychomotor treatment aims to promote the emotional-relational component, to overcome rigid divisions, and to integrate learning-related cognitive aspects with psychodynamic concepts. Finally, the goals of psychological and social support are to help the parents accept their child's handicap, understand the child's behavior, plan future pregnancies, and foster an environment for their child's integration.

A rare unbalanced translocation 1;18 in a child with epilepsy, mild dysmorphology and mental retardation.

A syndrome due to deletion of distal long arm of 1q was delineated by several groups. Up to now different terminal deletions 1q are described often clinically resulting in diagnosed mental retardation syndromes. We report on a 7-year-old male with distal monosomy 1q and additional genetic material on the short arm of chromosome 18. As expected, cytogenetic studies of the infant and his mother showed that the altered regions result from an unbalanced translocation of part of the long arm of chromosome 1. Comparison of our patient's data with those previously reported reveals neurological similarities but an unique genotype-phenotype correlation. The importance of a following better molecular characterization through array comparative genomic hybridization and especially the DNA sequence analysis around its breakpoints are discussed.

Primary nocturnal enuresis and learning disability.

AIM: Primary nocturnal enuresis (PNE) is the most common sleep disorder in developmental age, with a prevalence of 6-10% between 5 and 16 years of age, impacting on normal emotional and relational developing. Assessing the prevalence of mild learning disorders in enuretic children and the role of enuresis as risk factor to develop them. METHODS: Twenty-five patients (14 males) aged 7.59 referred for primary nocturnal enuresis to Sleep Disorder Center for developmental age and Nocturnal Enuresis of Second University of Naples (frequency ≥3/week), were enrolled in study. Reading abilities were evaluated using MT (Memory and Learning Transfer) and cognitive performance was assessed using Wechsler Intelligence Scale for Children-Revised version to excluded the subjects with IQ≤75. The control group consisted in 54 children (23 males) matched for age and sex distribution recruited in Campania region schools. Chi Square test was used to verify the different prevalence of academic problems in group of bedwetters and healthy controls. The P level was set at <0.05 for statistical significance. A logistic regression analysis was performed in order to assess the risk of developing learning disabilities by being enuretic. RESULTS: Learning difficulties were present in 18 enuretic and in 7 healthy children (χ2 24.873; P<0.001). χ2 test showed a statistic relevant difference in prevalence of "Attention request" (χ2 20.058; P<0.001) and "Border-line level" (χ2 12.979, P<0.001) identified in mild reading learning disorders in bedwetters respect of control group. Logistic regression analysis showed a strong increase to have mild academic impairment due to be a enuretic with an odd ratio (OR) of 17.26 (CI95% 5.30-56.19). CONCLUSION: Our study shows the higher pre-valence of mild reading difficulties in enuretic children than controls.

Cosleeping in childhood migraine.

AIM: Cosleeping is the practice of parents and children sleeping together in body contact for all or part of the night. There is a close relationship between sleep habits and headache disorders. Aim of the study was to identify prevalence of cosleeping in children with migraine disorder. METHODS: A total of 181 school-aged children referred to Headache Center for Developmental Age for Migraine without aura (MoA). Sex and age matched control group consists of 729 children recruited in schools in Campania. RESULTS: Cosleeping's prevalence is higher in children with MoA than in the control group (P=0.003) and an OR of 2.32 (95% CI 1.36-3.97). CONCLUSION: At our knowledge, our study is the first specific on prevalence of cosleeping in MoA school-aged children and show the importance of migraine power to invade all aspect of life of children affecting also their family management.

A case of femoral-facial syndrome in a patient with autism spectrum disorders.

The Femoral hypoplasia - unusual facies syndrome (FHUF) or Femoral - facial syndrome (FFS) was at first described in 1975. Up to now about 60 cases have been reported. According to our knowledge only 4 cases have had congenital central nervous system's malformations, furthermore the main stages of psychomotor development are almost always reported as normal or slightly altered in early childhood. We describe the first case of autism spectrum disorders (ASD) in a patient with FFS, emphasizing that this rare association could be one of many unrecognized underlying features.

The quality of life of children with pervasive developmental disorders.

AIM: Quality of life is increasingly the focus of attention by health, psychological and social services. Pervasive developmental disorders (PDD) are a group of psychiatric conditions in which the patient's clinical case history is characterized by disturbances in social interaction, deterioration of verbal and non-verbal communication, and presence of bizarre, limited and stereotyped activity. These disturbances affect multiple developmental areas and show up in very early stages of development, resulting in a permanent disorder. Many studies have sought to recognize causes and interventions for persons with PDD, however, they often take insufficient account of the effects these disorder can have on the lifestyle of patients and their families. These clinical case histories are so pervasive that they cause a disorder which upsets the equilibrium of the person's entire life. The aim of this study was to assess the effect of living with PDD on the person's quality of life and to highlight the factors that impact on the person and his/her family. METHODS: Both parents of 54 subjects (46 males and 8 females; age range 4-28 years) with diagnosed PDD (43 with autistic disorder, 2 with childhood disintegrative disorder, 3 with Asperger Syndrome, 6 with pervasive development disorder NAS) were enrolled in the study. The subjects affected with PDD were recruited at the AGSAS Onlus and IsMeC. Diagnosis was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders. Quality of life was assessed using the Italian version of the Impact of Childhood Illness Scale (Hoare and Russell, 1995). This scale consists of 30 questions that investigate the effect of illness on children, parents and families. For each question, the parent was asked to rate two variables: frequency and importance. Another questionnaire was administered to obtain medical history, diagnostic and therapeutic data of the persons with PDD. RESULTS: Analysis of frequencies and percentages of questionnaire answers showed that the most important problems related to illness; specifically, according to the Frequency and Importance Parameters, the problems centered around self-care skills, difficulty in explaining the child's illness to others and looking after the child. The most important problems about the other children in the family concerned providing them with necessary attention and the restrictions their brother/sister's illness placed on their own activities. No significant correlations emerged between diagnosis type and answers on individual subscale items (Pearson's r). CONCLUSIONS: Our data show that PDD has a considerable impact on both the child's development and the entire family. Parents' answers demonstrated that their child's illness had consequences for the child and how the family coped with it. For this reason, attention should be directed at psychological and social aspects, as well as attitudes, manners, reactions and effects such disturbances can have on the entire family.

People with Down's sindrome: adolescence and the journey towards adulthood.

AIM: Sexuality in disabled people is faced with difficulty and inadequateness, if not with complete refusal, the result being that young disabled people are often relegated to a destiny of solitude and abandon. This is even more true when the disability includes mental retardation. METHODS: Twenty-five youngsters between the age of 13 and 25 years 14 males (56%) and 11 females (44%) were recruited together with their mothers for this study. All attend the Family Association for Down people in Palermo. The youngsters with Down's syndrome were invited to carry out a drawing activity and then to describe what they had drawn. The mothers, on the other hand, replied to a semi-structured interview, the contents of which were organised into three areas: 1) the reaction of parents when the doctors communicate the birth of a child with Down's syndrome; 2) parents and the sexuality of a child with Down's syndrome; 3) the expectations of parents with regard to the future of their child with Down's syndrome. RESULTS: The free designs and their description demonstrated a clear emergence of themes that regard sexuality in 6 protocols out of 25. In 9 cases out of 25 the reference to sexuality is hidden behind allusive designs and descriptions. Six protocols testify, even if indirectly referable to the theme of sexuality, the emergence of an autonomy conflict, typical of adolescents, which demonstrates the beginning of the transitory process towards adulthood. Only in four situations was a sexuality reference not interpretable in the productions of the children. The qualitative analysis of the interviews carried out with the mothers evidences how the theme of the sexuality of the disabled child is lived in a conflictual way by the parents. CONCLUSIONS: The results obtained lead to affirm that the ''question regarding sexuality'' is more problematic from the parents' point of view rather than from that child's. In this prospective, in order to advantage the parents, it is necessary to plan psychological and clinical interventions regarding an education to sexuality.