Dismantling the ability of CT and MRI to identify the target mismatch profile in patients with anterior circulation large vessel occlusion beyond six hours from symptom onset.

PURPOSE: Patients with large vessel occlusion and target mismatch on imaging may be thrombectomy candidates in the extended time window. However, the ability of imaging modalities including non-contrast CT Alberta Stroke Program Early Computed Tomographic Scoring (CT ASPECTS), CT angiography collateral score (CTA-CS), diffusion-weighted MRI ASPECTS (DWI ASPECTS), DWI lesion volume, and DWI volume with clinical deficit (DWI + NIHSS), to identify mismatch is unknown. METHODS: We defined target mismatch as core infarct (DWI volume) of < 70 mL, mismatch volume (tissue with TMax > 6 s) of ≥ 15 mL, and mismatch ratio of ≥ 1.8. Using experimental dismantling design, ability to identify this profile was determined for each imaging modality independently (phase 1) and then with knowledge from preceding modalities (phase 2). We used a generalized mixed model assuming binary distribution with PROC GLIMMIX/SAS for analysis. RESULTS: We identified 32 patients with anterior circulation occlusions, presenting > 6 h from symptom onset, with National Institute of Health Stroke Scale of ≥ 6, who had CT and MR before thrombectomy. Sensitivities for identifying target mismatch increased modestly from 88% for NCCT to 91% with the addition of CTA-CS, and up to 100% for all MR-based modalities. Significant gains in specificity were observed from successive tests (29, 19, and 16% increase for DWI ASPECTS, DWI volume, and DWI + NIHSS, respectively). CONCLUSIONS: The combination of NCCT ASPECTS and CTA-CS has high sensitivity for identifying the target mismatch in the extended time window. However, there are gains in specificity with MRI-based imaging, potentially identifying treatment candidates who may have been excluded based on CT imaging alone.

Comparison of parental estimate of developmental age with measured IQ in children with neurodevelopmental disorders.

BACKGROUND: Formal IQ tests are an important part of the diagnostic and needs-based assessment process for children with neurodevelopmental disorders. However, resources for such assessments are not always available. It has been suggested that parental estimates of their child's developmental age could serve as a proxy IQ when formal measures are unavailable. METHOD: Parental estimates of their child's developmental age were converted to a developmental quotient (DQ) in 197 children with Autism Spectrum Disorder (ASD) aged 4-9 years, and 108 children with ADHD and intellectual disability (ADHD + ID) aged 7-15 years. Formal IQ assessments were then conducted. Parents completed the Social Communication Questionnaire ((SCQ), a measure of autism symptomatology) and a demographic questionnaire. RESULTS: In the ASD sample, 58% of parent estimates were within 15 points (i.e. one standard deviation) of the child's measured IQ score. Lower measured IQ and lower SCQ total score predicted higher parental accuracy. In the ADHD + ID sample, 74% of parental estimates were within 15 points of measured IQ. In this group, higher child IQ predicted greater parental accuracy. Parents in the ADHD + ID group were more likely to overestimate children's ability level than parents in the ASD group. CONCLUSIONS: In this study, the majority of parents of children with ADHD and ID were able to estimate their child's intellectual ability level with some accuracy. Parents of children with ASD were less accurate, but this may be because these parents were focussing more on children's level of adaptive functioning, which is known to be typically lower than cognitive ability in ASD.

CT colonography at low tube potential: using iterative reconstruction to decrease noise.

AIM: To determine the level of iterative reconstruction required to reduce increased image noise associated with low tube potential computed tomography (CT). MATERIALS AND METHODS: Fifty patients underwent CT colonography with a supine scan at 120 kVp and a prone scan at 100 kVp with other scan parameters unchanged. Both scans were reconstructed with filtered back projection (FBP) and increasing levels of adaptive statistical iterative reconstruction (ASiR) at 30%, 60%, and 90%. Mean noise, soft tissue and tagged fluid attenuation, contrast, and contrast-to-noise ratio (CNR) were collected from reconstructions at both 120 and 100 kVp and compared using a generalised linear mixed model. RESULTS: Decreasing tube potential from 120 to 100 kVp significantly increased image noise by 30-34% and tagged fluid attenuation by 120 HU at all ASiR levels (p<0.0001, all measures). Increasing ASiR from 0% (FBP) to 30%, 60%, and 90% resulted in significant decreases in noise and increases in CNR at both tube potentials (p<0.001, all comparisons). Compared to 120 kVp FBP, ASiR greater than 30% at 100 kVp yielded similar or lower image noise. CONCLUSIONS: Iterative reconstruction adequately compensates for increased image noise associated with low tube potential imaging while improving CNR. An ASiR level of approximately 50% at 100 kVp yields similar noise to 120 kVp without ASiR.

Speech, communication and use of augmentative communication in young people with cerebral palsy: the SH&PE population study.

BACKGROUND: Communication is frequently impaired in young people (YP) with bilateral cerebral palsy (CP). Important factors include motoric speech problems (dysarthria) and intellectual disability. Augmentative and Alternative Communication (AAC) techniques are often employed. The aim was to describe the speech problems in bilateral CP, factors associated with speech problems, current AAC provision and use, and to explore the views of both the parent/carer and young person about communication. METHODS: A total population of children with bilateral CP (n = 346) from four consecutive years of births (1989-1992 inclusive) with onset of CP before 15 months were reassessed at age 16-18 years. Motor skills and speech were directly assessed and both parent/carer and the young person asked about communication and satisfaction with it. RESULTS: Sixty had died, eight had other conditions, 243 consented and speech was assessed in 224 of whom 141 (63%) had impaired speech. Fifty-two (23% of total YP) were mainly intelligible to unfamiliar people, 22 (10%) were mostly unintelligible to unfamiliar people, 67 (30%) were mostly or wholly unintelligible even to familiar adults. However, 89% of parent/carers said that they could communicate 1:1 with their young person. Of the 128 YP who could independently complete the questions, 107 (83.6%) were happy with their communication, nine (7%) neither happy nor unhappy and 12 (9.4%) unhappy. A total of 72 of 224 (32%) were provided with one or more types of AAC but in a significant number (75% of 52 recorded) AAC was not used at home, only in school. Factors associated with speech impairment were severity of physical impairment, as measured by Gross Motor Function Scale level and manipulation in the best hand, intellectual disability and current epilepsy. CONCLUSIONS: In a population representative group of YP, aged 16-18 years, with bilateral CP, 63% had impaired speech of varying severity, most had been provided with AAC but few used it at home for communication.

Ensuring successful admission to hospital for young people with learning difficulties, autism and challenging behaviour: a continuous quality improvement and change management programme.

BACKGROUND: Children and young people with autism spectrum conditions frequently have adverse experiences in accessing health care. METHODS: An audit of experiences of families known to our tertiary service and hospital staff was conducted. A checklist asking about particular aspects of behaviour and communication was developed and incorporated into pre-admission planning. RESULTS: Awareness of the child/young person's communication needs and behaviours, plus good preplanning by all staff involved and a team member allocated to ensure that the care plan is carried through, has resulted in a vastly improved 'patient experience' from the perspective of family and staff. CONCLUSION: Children and young people with autism spectrum disorder, often with co-existing learning difficulties, vary greatly in their reactions to hospital admission. Preplanning that involves the family with a dedicated informed staff member can dramatically reduce distress and improve the patient and staff experience.

IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP).

BACKGROUND: Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of 'peaks' and 'troughs' at the subtest level. However, there are few data from epidemiological studies. METHOD: Comprehensive clinical assessments were conducted with 156 children aged 10-14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population. RESULTS: Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no 'peak' in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ. CONCLUSIONS: In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.

Sentence repetition in adolescents with specific language impairments and autism: an investigation of complex syntax.

BACKGROUND: Recent studies have indicated that many children with autism spectrum disorders present with language difficulties that are similar to those of children with specific language impairments, leading some to argue for similar structural deficits in these two disorders. AIMS: Repetition of sentences involving long-distance dependencies was used to investigate complex syntax in these groups. METHODS & PROCEDURES: Adolescents with specific language impairments (mean age = 15;3, n = 14) and autism spectrum disorders plus language impairment (autism plus language impairment; mean age = 14;8, n = 16) were recruited alongside typically developing adolescents (mean age = 14;4, n = 17). They were required to repeat sentences containing relative clauses that varied in syntactic complexity. OUTCOMES & RESULTS: The adolescents with specific language impairments presented with greater syntactic difficulties than the adolescents with autism plus language impairment, as manifested by higher error rates on the more complex object relative clauses, and a greater tendency to make syntactic changes during repetition. CONCLUSIONS & IMPLICATIONS: Adolescents with specific language impairments may have more severe syntactic difficulties than adolescents with autism plus language impairment, possibly due to their short-term memory limitations.

Utility of Percentage Signal Recovery and Baseline Signal in DSC-MRI Optimized for Relative CBV Measurement for Differentiating Glioblastoma, Lymphoma, Metastasis, and Meningioma.

BACKGROUND AND PURPOSE: The percentage signal recovery in non-leakage-corrected (no preload, high flip angle, intermediate TE) DSC-MR imaging is known to differ significantly for glioblastoma, metastasis, and primary CNS lymphoma. Because the percentage signal recovery is influenced by preload and pulse sequence parameters, we investigated whether the percentage signal recovery can still differentiate these common contrast-enhancing neoplasms using a DSC-MR imaging protocol designed for relative CBV accuracy (preload, intermediate flip angle, low TE). MATERIALS AND METHODS: We retrospectively analyzed DSC-MR imaging of treatment-naïve, pathology-proved glioblastomas (n = 14), primary central nervous system lymphomas (n = 7), metastases (n = 20), and meningiomas (n = 13) using a protocol designed for relative CBV accuracy (a one-quarter-dose preload and single-dose bolus of gadobutrol, TR/TE = 1290/40 ms, flip angle = 60° at 1.5T). Mean percentage signal recovery, relative CBV, and normalized baseline signal intensity were compared within contrast-enhancing lesion volumes. Classification accuracy was determined by receiver operating characteristic analysis. RESULTS: Relative CBV best differentiated meningioma from glioblastoma and from metastasis with areas under the curve of 0.84 and 0.82, respectively. The percentage signal recovery best differentiated primary central nervous system lymphoma from metastasis with an area under the curve of 0.81. Relative CBV and percentage signal recovery were similar in differentiating primary central nervous system lymphoma from glioblastoma and from meningioma. Although neither relative CBV nor percentage signal recovery differentiated glioblastoma from metastasis, mean normalized baseline signal intensity achieved 86% sensitivity and 50% specificity. CONCLUSIONS: Similar to results for non-preload-based DSC-MR imaging, percentage signal recovery for one-quarter-dose preload-based, intermediate flip angle DSC-MR imaging differentiates most pair-wise comparisons of glioblastoma, metastasis, primary central nervous system lymphoma, and meningioma, except for glioblastoma versus metastasis. Differences in normalized post-preload baseline signal for glioblastoma and metastasis, reflecting a snapshot of dynamic contrast enhancement, may motivate the use of single-dose multiecho protocols permitting simultaneous quantification of DSC-MR imaging and dynamic contrast-enhanced MR imaging parameters.

Moving Toward a Consensus DSC-MRI Protocol: Validation of a Low-Flip Angle Single-Dose Option as a Reference Standard for Brain Tumors.

BACKGROUND AND PURPOSE: DSC-MR imaging using preload, intermediate (60°) flip angle and postprocessing leakage correction has gained traction as a standard methodology. Simulations suggest that DSC-MR imaging with flip angle = 30° and no preload yields relative CBV practically equivalent to the reference standard. This study tested this hypothesis in vivo. MATERIALS AND METHODS: Eighty-four patients with brain lesions were enrolled in this 3-institution study. Forty-three patients satisfied the inclusion criteria. DSC-MR imaging (3T, single-dose gadobutrol, gradient recalled-echo-EPI, TE = 20-35 ms, TR = 1.2-1.63 seconds) was performed twice for each patient, with flip angle = 30°-35° and no preload (P-), which provided preload (P+) for the subsequent intermediate flip angle = 60°. Normalized relative CBV and standardized relative CBV maps were generated, including postprocessing with contrast agent leakage correction (C+) and without (C-) contrast agent leakage correction. Contrast-enhancing lesion volume, mean relative CBV, and contrast-to-noise ratio obtained with 30°/P-/C-, 30°/P-/C+, and 60°/P+/C- were compared with 60°/P+/C+ using the Lin concordance correlation coefficient and Bland-Altman analysis. Equivalence between the 30°/P-/C+ and 60°/P+/C+ protocols and the temporal SNR for the 30°/P- and 60°/P+ DSC-MR imaging data was also determined. RESULTS: Compared with 60°/P+/C+, 30°/P-/C+ had closest mean standardized relative CBV (P = .61), highest Lin concordance correlation coefficient (0.96), and lowest Bland-Altman bias (µ = 1.89), compared with 30°/P-/C- (P = .02, Lin concordance correlation coefficient = 0.59, µ = 14.6) and 60°/P+/C- (P = .03, Lin concordance correlation coefficient = 0.88, µ = -10.1) with no statistical difference in contrast-to-noise ratios across protocols. The normalized relative CBV and standardized relative CBV were statistically equivalent at the 10% level using either the 30°/P-/C+ or 60°/P+/C+ protocols. Temporal SNR was not significantly different for 30°/P- and 60°/P+ (P = .06). CONCLUSIONS: Tumor relative CBV derived from low-flip angle, no-preload DSC-MR imaging with leakage correction is an attractive single-dose alternative to the higher dose reference standard.

Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans.

Electrophysiology and optical indicators have been used in vertebrate systems to investigate excitable cell firing and calcium transients, but both techniques have been difficult to apply in organisms with powerful reverse genetics. To overcome this limitation, we expressed cameleon proteins, genetically encoded calcium indicators, in the pharyngeal muscle of the nematode worm Caenorhabditis elegans. In intact transgenic animals expressing cameleons, fluorescence ratio changes accompanied muscular contraction, verifying detection of calcium transients. By comparing the magnitude and duration of calcium influx in wild-type and mutant animals, we were able to determine the effects of calcium channel proteins on pharyngeal calcium transients. We also successfully used cameleons to detect electrically evoked calcium transients in individual C. elegans neurons. This technique therefore should have broad applications in analyzing the regulation of excitable cell activity in genetically tractable organisms.

Back to the future: developing hypotheses on the effects of climate change on ovine parasitic gastroenteritis from historical data.

Although the influence of temperature and moisture on the free-living stages of gastrointestinal nematodes has been described in detail, and evidence for global climate change is mounting, serious attempts to relate altered incidence or seasonal patterns of disease to climate change are lacking. In Great Britain, veterinary surveillance laboratory diagnoses of ovine parasitic gastroenteritis (PGE) have been categorised in species groups and recorded since 1975. Here we present a detailed analysis of these historical data. Over the past 5-10 years, highly significant increases in the overall rate of diagnosis of PGE were observed for all species categories. After identifying and analysing possible sources of bias, the effect of climate change on parasite epidemiology proved the most likely explanation for the observed patterns, although other hypotheses could not be refuted. Seasonal rates of diagnosis suggest that, in line with increases in temperature, fewer larvae of Teladorsagia and Trichostrongylus species survive the winter and spring at pasture, while the windows of transmission of these species, and of Haemonchus contortus, have extended into the autumn. For all species categories significant differences in rates of diagnosis, and in the seasonality of disease, were identified between regions. Nematodirosis showed a pronounced peak in spring and early summer in Scotland while in the Southwest, where fewer diagnoses were made, it also appeared regularly at other times of year. The data presented serve as a baseline against which future changes can be measured.

Travel time and cancer care: an example of the inverse care law?

INTRODUCTION: There is growing evidence that in rural areas cancer mortality is higher and referral occurs later, indicating different patterns of care. In Scotland services to rural areas have been organized through 'managed clinical networks'. In some cases, these organizational networks have been structured so that the referral hospital is not the one nearest to the patient's home. This study set out to discover if access to cancer specialist care in mainland Scotland altered with distance to tertiary care facilities. The aim was to explore the relationship between hospital admission rates, type of hospital and travel time. METHODS: Retrospective analysis of all registered cancers in Scotland over the three-year period 2000-2002, examining incidence rates and accessibility of care over 3 years, measured by hospital discharge rates (equivalent to admission rates) and mean bed days for cancer patients. RESULTS: The type of hospital to which a cancer patient was admitted and the duration of admission varied with travel distance from a patient's home. All patients travelling more than one hour had lower admission rates to a specialist cancer centre. Those travelling more than 3 hours were not always admitted to the facility nearest their home address and were admitted for significantly fewer days than all other groups. CONCLUSION: Differences in tertiary cancer care obtained may explain some of the reasons behind late presentation and higher mortality rates. This study provides evidence that the recognized increased cancer mortality in rural patients is indeed compounded by an increased travel burden.

Corynebacterium pseudotuberculosis and its role in ovine caseous lymphadenitis.

Caseous lymphadenitis (CLA) of sheep, caused by Corynebacterium pseudotuberculosis, has been a significant disease in the majority of sheep-rearing regions for over a century. Because of the chronic and often sub-clinical nature of the infection, it has proved difficult to control and prevalence is high in many parts of the world, which in turn leads to significant economic losses for farmers. This review describes the important characteristics of C. pseudotuberculosis and examines the pathogenesis and epidemiology of the infection in sheep. The review also discusses the immune response to infection and describes the methods that have been developed to control CLA, with particular emphasis on the use of vaccination and serological testing.

Echocardiographic Pulmonary Hypertension Predicts Post-transplantation Renal Allograft Failure.

BACKGROUND: Pulmonary hypertension in the setting of renal transplantation has been associated with early allograft dysfunction and increased mortality, but this relationship has not been extensively studied. METHODS: We performed a retrospective cohort study of adult patients who underwent their first renal transplantation in the years 2003-2009 and had pre-transplantation echocardiograms. Pulmonary hypertension was defined as right ventricular systolic pressure ≥40 mm Hg in the absence of left-sided valvular disease and/or left ventricular ejection fraction ≤50%. Eighty-two of 205 patients (40%) met the inclusion criteria. The relationship between pulmonary hypertension and death-censored allograft failure (hemodialysis dependence or retransplantation) and serum creatinine was assessed with the use of Cox hazard regression and generalized mixed models. RESULTS: The presence of pulmonary hypertension was associated with a 3-fold increase in the risk of death-censored allograft failure (95% confidence interval, 1.20-7.32; P = .02). Failure rates were 19% at 24 months and 51% at 96 months for those with pulmonary hypertension versus 7% at 24 months and 20% at 86 months for those without pulmonary hypertension (P = .01). Among those without graft failure, there was an increase in creatinine levels after transplantation (P = .01). Effect estimates were unchanged by adjustment for multiple covariates and when pulmonary hypertension was defined as right ventricular systolic pressure ≥36 mm Hg. CONCLUSIONS: Pulmonary hypertension before renal transplantation carries a 3-fold increased risk of death-censored allograft failure. The relationship between the pulmonary circulation and renal allograft failure warrants further study.

Recent advances in technology for measuring and manipulating cell signals.

Signal transduction research has made some glowing progress in the past 12 months. Recent advances in fluorescent proteins, small molecule fluorophores and imaging technology are generating new ways to investigate signal transduction.

Bladder and bowel continence in bilateral cerebral palsy: A population study.

INTRODUCTION: The attainment of continence is an important milestone in all children, including those with disability. OBJECTIVE: To describe the age of bladder and bowel continence in children with bilateral cerebral palsy (BCP), and the association with intellectual impairment (II) and severity of motor disability. PATIENTS AND METHODS: The parents of 346 children with BCP were interviewed as part of a population-based prospective study of the children at 3, 7, and 17 years of age. The age of bladder and bowel continence by day and night was ascertained and compared with controls from the Avon Longitudinal Study of Parents and Children (ALSPAC). RESULTS: The median age for daytime bladder and bowel continence in BCP children was 5.4 years compared with 2.4 years in the controls. At 13.8 years of age, 59.4% of BCP children and 99% of controls were continent by day. In BCP children, there was no difference between the attainment of daytime bladder and bowel control. Night-time bladder and bowel control was slower and less completely attained, with 50% of BCP children continent by the age of 11.8 years compared with 3 years in control children. At 13.8 years of age, 51.9% of BCP children compared with 99.4% of controls were continent for bowel and bladder at night. Gross Motor Functional Classification Score (GMFCS) and intellectual ability (IA) (II) were strongly associated with continence attainment (P < 0.0001), but gender was not. DISCUSSION: Delayed and less complete continence attainment was noted in other clinic series of children with cerebral palsy (including hemiplegics) and children with II. Severity of motor disability (GMFCS), and II impacted on other aspects of toilet training, such as: motivation, understanding, communication, and independence skills. The presence of neurogenic bladder and bowel dysfunction can occur in all levels of GMFCS. Thus, there are many reasons that can prevent continence attainment. CONCLUSIONS: Children with BCP achieved day and night-time bladder and bowel continence more slowly and less completely than controls, with 60.8% being continent by day and 54.6% by night at the age of 17 years. The majority of BCP children who were continent by day had achieved this by the age of 5.5 years (86%). At least 88% of BCP children with GMFCS I/II and normal, specific or mild learning impairment were continent for bladder and bowel by day and night. Expectations should be shared with parents, and failure to attain expected continence should be actively investigated.

Elephants in Pyjamas: Testing the Weak Central Coherence Account of Autism Spectrum Disorders Using a Syntactic Disambiguation Task.

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status.

A 2359-base pair DNA fragment from Cryptosporidium parvum encoding a repetitive oocyst protein.

A Cryptosporidium parvum lambda gt11 expression library was constructed using EcoRI-digested genomic DNA extracted from in vitro-excysted oocysts. Screening of this library with rat anti-Cryptosporidium antiserum led to the isolation of a clone containing a 2359-bp EcoRI fragment. When this fragment was ligated into the EcoRI site of plasmid vector pMS1S, the resulting clone expressed a 200-kDa beta-galactosidase fusion protein. Western blot analysis using serum raised against this fusion protein indicated that the EcoRI fragment represented part of a gene encoding a 190-kDa oocyst wall protein of C. parvum. Sequencing of the fragment revealed a continuous open reading frame encoding 786 amino acids. The DNA sequence is relatively low in G+C (39.1%), and the third codon position contains only 17.9% G+C. The deduced peptide sequence has unusually high proportions of cysteine, proline, glutamine and histidine. Another striking feature of the amino acid sequence is the presence of distinctly repetitive regions based on conserved cysteine residues.

Support for linkage of autism and specific language impairment to 7q3 from two chromosome rearrangements involving band 7q31.

Childhood autism is characterised by impairments in communication and reciprocal social interaction together with restricted/stereotyped interests, which are evident before 3 years of age. Specific developmental disorders of speech and language (SDDSL) are characterised by impairment in the development of expressive and/or receptive language skills which is not associated with intellectual, sensory, physical, or neurological impairment. Family and twin studies indicate a substantial genetic component in the aetiology of both disorders. They also reveal increased rates of SDDSL in relatives of autistic individuals, suggesting that this phenotype can represent one manifestation of the genetic liability for autism. Modelling of the recurrence risk for autism and milder phenotypes, such as SDDSL, suggest that three or four epistatic loci may be aetiologically involved. A recently published linkage study of an exceptional family with an apparently dominantly inherited SDDSL implicated chromosome band 7q31 as the site of the putative susceptibility locus (SPCH1). This region of chromosome 7 also shows strong linkage in multiplex families with autism. We present two individuals (one has autism, the other SDDSL) with different, apparently balanced chromosome rearrangements involving a breakpoint at 7q31.3. Fluorescence in situ hybridisation was used to localise the breakpoints to an approximately 1 cM interval between CFTR and D7S643. Our findings may be of interest and relevance to the genetic aetiology of autism, and helpful in the search for susceptibility loci for SDDSL and autism. Am. J. Med. Genet. (Neuropsychiatr. Genet. ) 96:228-234, 2000.