Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B.

Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

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.

Occipital intermittent rhythmic delta activity only following eye closure in atypical CNS Salmonellosis.

OBJECTIVE: A statement recently published on the base of a large retrospective analysis, report that the occipital intermittent rhythmic delta activity (OIRDA) "is associated with epilepsy but not acute encephalopathy" [Gullapalli and Fountain. J Clin Neurophysiol 2003;20:35-41]. Our aim is to report, the exception from a child with an intermittent fever, in which the finding of an occipital intermittent rhythmic delta activity (OIRDA) following the eye closure in the EEG recording was the first clinical sign addressing to a CNS involvement. METHODS: To review the record from a five-year-old girl with a normal basal electroencephalogram and OIRDA that only appeared following eye closure. RESULTS: We found OIRDA associated with atypical CNS Salmonellosis. Brain MRI and CSF examination confirmed an acute encephalopathy, which was due to Salmonella infection. The only symptoms of the infection were episodes of nightly fever that had lasted for four weeks, sometimes associated with headache and vomiting. Both OIRDA only induced by eye closing and other symptoms disappeared after starting antimicrobial therapy. CONCLUSIONS: OIRDA only following eye closure is a non-specific abnormality and the present findings, based on a single case, merely indicate that intracranial infection is among the possible causes. SIGNIFICANCE: The new clinical association is certainly worth recording, as the presence of this electrophysiological sign may provoke clinicians to then delve further into a diagnostic work up.

Char syndrome: an additional family with polythelia, a new finding.

This report describes a father and daughter with Char syndrome, a rare autosomal dominant disorder. Both affected individuals had typical face, strabismus, and foot anomalies. The girl also had a patent ductus arteriosus. In addition, both patients had polythelia (supernumerary nipples), a finding not described before in the Char syndrome.

Corpus callosum agenesis, multiple cysts, skin defects, and subtle ocular abnormalities with a de novo mutation [45,XX,der(5), t(5;;14) (pter;q11.2)].

We report on a 2-year-old girl with a de novo mutation [45,XX,der(5),t(5;14) (pter;q11.2)] with corpus callosum agenesis, multiple cysts (cerebral and cardiac), subtle eye abnormalities, and at least two different skin defects, strongly indicating neuroectodermal involvement, as a neuromuscular choristoma (hamartoma) and an eccrine hamartoma. Fluorescent in situ hybridization with different single-locus probes showed that chromosome 5 has a very small deletion, confined to a region composed of repetitive sequences. By contrast, the long (q) arm of chromosome 14 seems to be much more involved in the rearrangement, with partial monosomy spanning from the centromere to the D14S72 and D14S261 loci. The extent of the deleted region of chromosome 14 is approximately 16 cM. To our knowledge, this is the smallest reported deletion involving the chromosome 14q11.2 region to be associated with a developmental disorder resulting in variable eye, skin, and brain anomalies. We suggest that a new syndrome, mimicking in some ways the MLS phenotype, is caused by a deletion in the chromosome 14q11.2 region.

The varicella vaccine. An evolving mosaic of information.

The Oka strain of live attenuated varicella vaccine has been under evaluation for license for many years. Nevertheless, despite more than 20 years of research efforts, only few countries, up-to-day, licensed this vaccine. Notwithstanding numerous studies have indicated that the vaccine is safe, immunogenic and highly protective against severe varicella in healthy children and adults and in certain immunocompromised patients, including children with leukemia, there are some controversial aspects that could explain the lacking diffusion of the vaccine. In this study, some main question have been reviewed: 1) how the vaccine should be used; 2) how much the vaccine is powerful; 3) how we should manage the immunodeficient patient: 4) how much the vaccine virus could be dangerous for the disease transmission; 5) why the vaccine is better than the immune-globulins; 6) which is the best timing for immunization; 7) why we are still waiting to start the universal immunization.

New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6.

The paper describes events that in the last fifteen years, have led to the identification of the aetiological agents of three widely known diseases: cat scratch disease, erythema infectiosum and exanthem subitum. The particular features of Afipia felis and Rochalimaea, Parvovirus B 19 and Herpesvirus 6 are presented. The paternity of new diseases (i.e. bacillary angiomatosis, bacillary peliosis hepatitis, LES-like syndrome, chronic fatigue syndrome, petechial glove and sock syndrome, etc.) has also been attributed to some of these pathogens as has the paternity of some older ones (i.e. aplastic crisis, erythroblastosis fetalis, trench fever, hepatitis, opportunistic infection, etc.). It has been argued that the same pathogen can cause different diseases depending on the immunogenic state of the subject. To date, persisting difficulties in isolating the pathogen or differentiating between latent or active infection, still in some cases raises doubts concerning the attribution of the disease to a specific agent. New immunological or molecular techniques, allowing the direct detection of in vivo replication, are still needed in order to establish a sure connection between some of these agents and some of these diseases. Progress here will both give more accurate data about the epidemiology of some diseases and allow us to apply more appropriate treatment and prevention techniques.

Vagal and hypoglossal Bell's palsy.

A 7-year-old boy was referred because of a sudden change to nasal speech, dysarthria for words with explosive consonants in speech, and nasal regurgitation of fluids. The symptoms arose over 1 week following a capricious episode of acute asthmatic bronchitis. Physical and neurologic examinations were normal except for a left deviation of the uvula, accompanied by a "curtain" movement of the posterior pharyngeal wall against the opposite side, and a left deviation of the protruded tongue. No vascular, traumatic, infectious, neoplastic, or neurologic causes could be identified. No therapy was administered. Full recovery occurred 4 months later. The diagnosis was idiopathic vagal and right hypoglossal nerve palsy (Bell's palsy).

Does puberty interfere with asthma?

This study reviews whether, to date, scientific evidence exists that puberty interferes with the occurrence of asthma. This question was triggered by three points: (a) clinical experience with asthma as a relatively benign disease that children often 'grow out of'; (b) observations implying that asthma can change during fluctuations of sexual steroid hormones; and (c) knowledge that puberty is an age of deep hormonal changes. No scientific evidence was found that pubertal changes interfere with the occurrence of asthma. Nevertheless, there is a general agreement about the influence of age and sex on its outcome. The overall occurrence of the disease, which is highest in childhood, declines with age. In the wane phenomena, puberty does not seem to be more important than previous ages. Furthermore, the pattern of occurrence is different in the two sexes. Boys have more asthma before 10 years of age or the mid-teens. Girls then overtake boys and have more asthma up to the years of sexual maturity. During the fifth or sixth decade, asthma again seems to become slightly more prevalent in men than women, or at least the difference between the sexes disappears. It is concluded that the risk of asthma is not influenced by puberty. Age and sex seem to be more important factors, although the reason for this is unknown.

MOMO syndrome: a possible third case.

This report describes a 5-year-old girl, mildly mentally retarded, with the following characteristics: macrocephaly; severe obesity; ocular abnormalities (right optic disk coloboma and left choroidal coloboma); short stature; and recurvation of the femur. The case is sporadic with no consanguinity between the parents. The condition was diagnosed tentatively as MOMO syndrome (Macrosomia, Obesity, Macrocephaly, and Ocular Abnormalities) (MIM, 157980), because of the presence of short stature, in contrast with the large stature of the only two previously described cases. It is the third possible example of this rare syndrome to be described in the literature, with some new clinical findings presented.

Hepatitis B vaccine: current issues.

OBJECTIVE: To review two main issues concerning the hepatitis B vaccine: (1) the management of unresponsive subjects and (2) the need for routine booster doses. DATA SOURCES: Pertinent literature identified via MEDLINE (1980-1996) search as well as references cited in published articles. DATA SYNTHESIS: The optimal procedure for management of subjects unresponsive to hepatitis B vaccine has not been well established. Most unresponsive subjects are not absolute nonresponders, since most of them can develop protective concentrations of antibodies to hepatitis B surface antigen (anti-HBsAg) after hepatitis B revaccination, consisting of a fourth or a fifth dose or a new complete course of immunization. In subjects who do not respond to the hepatitis B vaccine after four or more injections, the benefits of the combination of cytokines (e.g., interferon-alfa, interleukin-2 [aldesleukin]) and vaccine have not been clearly shown. There are two main opinions regarding the need for routine booster doses. Experts from the US, claiming long-term protection from immunologic memory, suggest delaying booster doses for at least a decade after vaccination in subjects with normal immune status. Furthermore, postvaccination antibody testing should be restricted only to high-risk subjects. Once a vaccinated subject has responded satisfactorily, further antibody tests are unnecessary. Only hemodialysis patients should be tested annually for adequate antibody concentrations and the booster dose administered when concentrations decline to less than 10 IU/L. Experts from Europe suggest that vaccine-induced antibody responses should be assessed in all subjects and booster doses administered at intervals, with the theory being that protection correlates with the presence of antibody. However, indications about appropriate timing for booster doses and target titers of anti-HBsAg remain controversial. CONCLUSIONS: It is possible to obtain seroconversion in nonresponders by using variations in vaccination strategies (i.e., > 3 doses, double amounts of HBsAg). Adjuvants such as interferon-alfa or aldesleukin are of limited use. The opinions of American experts regarding routine booster doses, as expressed by the statement of the Immunization Practices Advisory Committee, seem to be well defined and helpful to clinicians trying to resolve controversies for individual patients. The opinions of the European experts are not unanimous and are sometimes impractical. A consensus conference is needed.

Distribution of BMI in children: prevalence of wasting and fattening conditions.

This paper reports a study of body-mass index (weight/height2) frequency distribution in 2858 schoolchildren (1440 males, 1418 females), 6-14 years old: (a) not taking into account the degree of skewness (z-score) and (b) taking it into account (LMS method by Cole). The z-score detected no evident problems of severe wasting conditions, but did detect the presence of severe fattening conditions. The LMS method gave a more balanced distribution. Methods that do not take into account the degree of skewness should be avoided in estimates concerning prevalence of wasting and stunting conditions.

Waist percentiles: a simple test for atherogenic disease?

OBJECTIVE: To give standards for quantification of the magnitude of waist circumference in children. METHODS: We calculated the percentiles of waist circumference by age and sex from a sample of 2858 subjects (1440 males and 1418 females, aged 6-14 years). Data were from a population survey of 15,000 school-children in Pescara, a town in Abruzzo, a region of Central Italy. RESULTS: We reported the values of the calculated percentiles by age and sex and gave the smoothed percentile curves. CONCLUSIONS: Some recent studies in adults have indicated that measuring waist circumference seems to be the simplest way to estimate obesity and the risk of cardiovascular disease. In children, similar evidence is emerging. To date, no example of calculating standards has been published for quantitating the magnitude of waist circumference in children; therefore, our example of standard waist measurements could be used as a practical model for selecting subjects with a value of < or = or > 2 SD from the mean. The metabolic status should then be checked by complementary laboratory examination.

[Body mass index, weight and height in school children in central Italy]. / Body-mass index, peso e altezza di una popolazione scolastica dell'Italia centrale.

AIM: To study the pattern of distribution for body-mass index, weight and height in children of the Abruzzo region and to compare them with commonly used standards. STUDY DESIGN: Weight, height and body-mass index (BMI, weight/height2) were reported from 2858 school children (6 to 14 years old) of a town of Central Italy (Pescara). Data were detected in 1991. The conventional percentiles were calculated. Then we considered the first (25%), the median (50%) and the third (75%) quartile of all obtained data. Those of the BMI were superimposed on France (Rolland-cachera MF, Eur J Clin Nutr 1991;45:13) and USA (Hammer LD, Am J Dis Child 1991;145:259) standards. Those of weight and height were superimposed on the respective Tanner standards (Tanner JM, Arch Dis Child 1966;41:613). RESULTS: The percentiles are shown. The central point of distribution (quartiles) appear slid over. The nearer standard for BMI to our sample seems to be represented by France standards, in front of which our values result slid quite exactly of one quartile over. The comparison with USA standards shows an increase of our findings, but the slope of the curves is different (overall in the advanced ages). Both weight and height, compared with Tanner standards, show an increase of values. CONCLUSIONS: 1) Different growth patterns are observed in the studied sample; 2) to calculate the prevalence of wasting and fattening conditions using values of cutoff points from not own standards could load to not appropriate estimates.

Influence of age, sex, and BMI on waist-to-thigh circumference ratio in children.

In adults the distribution of body fat towards the central region seems a good predictor of disease and mortality. Central fat deposition tends to increase with age; sex and obesity further influence this trend. In children the distribution of adiposity to the central region is not well known. Recently, using circumferences of waist and thigh, we computed the percentile curves of the waist to thigh circumference ratio (WTR) from 2858 subjects (1440 males, 1418 females), 6-14-years-old (Zannolli, R., Chiarelli, F., and Morgese, G., 1993, International Journal of Obesity, 17 (Supplement 2), 60). In the present study, using the same sample of data, we showed that in lean, average or fat subjects, WTR is only weakly (< 5% of variance) explained by age, sex and body-mass index (in spite of the 'statistical significance' of sex and body-mass index in some groups). Hence, some subjects, among the lean, average and fat groups, could have a high (i.e. > 2 SD over the mean) WTR, independent of age, sex or weight. We therefore propose that the values of WTR should be checked against appropriate standards. Those with a WTR value greater than 2 SD from the mean, independent of age, sex or weight, should be studied more carefully, using anthropometry, so as to give early warning of those who are more prone to degenerative disease.