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BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.

Background: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. Methods: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. Results: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. Conclusion: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.

A patient is presented who developed a granulomatous hepatitis and pleuritis approximately 7 months after an ileal bypass procedure for morbid obesity. Although the etiological agent was presumed to be Mycobacterium tuberculosis no pathogenic organism was grown from the liver, pleura, bone marrow, sputum, or gastric aspirate. The possibly increased susceptibility of these patients to mycobacterial infections is discussed. The value of obtaining serum levels of ethambutol, isoniazid, and rifampin, in patients with malabsorption is stressed. Although this patient seemed to respond to antituberculous therapy, other possible causes for the granulomatous process are explored.

The SALL genes, similar to the Drosophila gene spalt ,1 encode likely zinc finger transcription factors. In humans, four such genes have been identified to date. Mutations in the gene SALL1 on chromosome 16q12.1 have been associated with Townes-Brocks syndrome and related phenotypes,2,3 and mutations in the gene SALL4 have been shown to be causative in patients with Okihiro syndrome.4,5 SALL2 6 and SALL3 7 remain to be associated with human disease. We previously reported frameshift and nonsense mutations in SALL4 in five of eight families segregating the Okihiro syndrome phenotype.5 A further report4 identified two frameshift mutations and one nonsense mutation in three affected kindreds, including the family reported by Okihiro et al .8 In a recent study of patients with a clinical diagnosis of Holt-Oram syndrome, one additional frameshift mutation and an unclear missense change were reported from a family who turned out to have Okihiro syndrome rather than Holt-Oram.9 Furthermore, we reported one previously identified and three novel SALL4 mutations in patients originally diagnosed as having either Holt-Oram syndrome (later revised to Okihiro syndrome based on the observation of a Duane anomaly in at least one of the affected family members in each family), acro-renal-ocular syndrome, or Holt-Oram syndrome versus thalidomide embryopathy.10 While our findings suggested that acro-renal-ocular syndrome and Okihiro syndrome are allelic, evidence so far has come only from one family in which no gross structural eye defects were seen.11 In order to further substantiate our findings we sought to perform mutation analysis in additional patients diagnosed with acro-renal-ocular syndrome, especially those who presented with structural eye defects. We were also interested in extending our studies to further patients with Okihiro syndrome in order to allow a genotype–phenotype correlation. Here we report five novel …