Screening for cognitive dysfunction in systemic lupus erythematosus: the Montreal Cognitive Assessment Questionnaire and the Informant Questionnaire on Cognitive Decline in the Elderly.

BACKGROUND: Cognitive dysfunction (CD) is among the most common neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Traditional neuropsychological testing and the Automated Neuropsychologic Assessment Metrics (ANAM) have been used to assess CD but neither is an ideal screening test. The Montreal Cognitive Assessment Questionnaire (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) are brief and inexpensive tests. This study evaluated the MoCA and IQCODE as screening tools. METHODS: SLE patients fulfilling American College of Rheumatology (ACR) classification criteria were evaluated using the ANAM as the reference standard. The performance characteristics of the MoCA and IQCODE were assessed in comparison with normal controls (NCs) and rheumatoid arthritis (RA) patients. Four different definitions of CD were utilized. RESULTS: In total, 78 patients were evaluated. MoCA and ANAM scores were significantly correlated ( r = 0.51, p < 0.001). At the optimal cutoff, the sensitivity of the MoCA was ≥ 90% (depending on definition of CD) vs RA patients and ≥83% vs NCs. ANAM and IQCODE scores did not correlate ( p = 0.8152). IQCODE sensitivities were low for both RA patients and NCs regardless of definition and cutoff used. CONCLUSION: The MoCA appears to be a promising and practical screening tool for identification of patients with SLE at risk for CD.

Homozygous nonsense mutation in SCHIP1/IQCJ-SCHIP1 causes a neurodevelopmental brain malformation syndrome.

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C-terminal region shared by the Schwanomin-Interacting Protein1 (SCHIP1) isoforms including the IQCJ-SCHIP1. The in vitro expression of SCHIP1 and IQCJ-SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full-length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ-SCHIP1 point mutation in humans associated with a neurological-developmental phenotype.

Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction?

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stüve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.

Risperidone-induced sexual dysfunction in a prepubertal child - a case report.

We report on a child with attention deficit hyperactivity disorder and motor tics, who developed frequent penile erections during treatment with risperidone and atomoxetine. On discontinuation of risperidone, he recovered fully. Clinicians should be alert to the adverse effects of atypical antipsychotics, which are used to treat a wide variety of paediatric psychiatric disorders.

Child psychiatry training for paediatric neurology trainees; a personal view.

The authors describe their experience to support the view that training in child psychiatry is an effective way for the paediatrician in training to gain an understanding of that specialty. It is also an efficient way to acquire certain skills, which will be helpful in the future, either in hospital or community paediatrics.

Genotype analysis of the NF1 gene in the French Canadians from the Québec population.

We genotyped 19 NF1 families from the French Canadians of the Québec population with six intragenic polymorphic markers including 2 RFLPs (EcoRI and RsaI) and 4 microsatellites (IVS26-2.3, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0). Genotype analysis indicated families 7610 and 7473 bear deletions. In Family 7610 the deletion removed the entire NF1 gene except exons 1 to 4b. The breakpoint of the deletion is located between exons 4a and 4b. The deletion 7473 was derived from the maternal chromosome and exons 1 to 5 were deleted. The breakpoint of the deletion is located between exons 7 and 13. Their phenotypes are reported. The allele frequencies of microsatellites IVS27AC28.4 and IVS38GT53.0 are compared to previously reported data from Caucasians, including Spanish and Italians. The difference is statistically significant (P < 0.0036) for marker IVS27AC28.4 between the Québec French Canadian and the Italian population.

Physical and transcriptional map of the mouse Chromosome 10 proximal region syntenic to human 6q16-q21.

Toward the isolation of the grey-lethal (gl) gene, we have genetically localized this locus on mouse Chromosome (Chr) 10 between the Fyn gene and the D10Mit148 microsatellite marker. Here, we have screened five yeast artificial chromosome (YAC) libraries and isolated more than 100 YAC clones mapping to this region. Forty-two clones were characterized and assembled in an approximately 8.5 megabases (Mb) contig showing high linkage conservation with the human 6q16-q21 interval. During this study, 24 specific novel sequence-tagged sites (STSs) were derived from YAC insert ends, and 15 mouse genes were precisely mapped to the contig. The physical and transcriptional map presented here will provide novel resources to isolate the gl locus associated with osteopetrosis, and will also provide candidate loci for other defects mapped on human Chr 6q.

The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast maturation/function.

The osteopetrotic grey-lethal (gl) mouse mutant displays many similarities to the human malignant autosomal-recessive form of osteopetrosis. In this study, we show that the gl osteopetrotic bone phenotype is characterized by the presence of numerous differentiated multinucleated osteoclasts. A significant increase in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was detected in vivo, suggesting induction of differentiation in the osteoclast lineage as a compensatory mechanism. These gl osteoclast cells demonstrated a defective cytoskeletal reorganization and an underdeveloped ruffled border, a membrane structure essential for active bone resorption. Accordingly, resorption activity of these cells is markedly impaired by four- to tenfold as evaluated with the pit formation assay. This low bone resorption in gl osteoclasts is highly reminiscent of the loss in key enzymes, V-ATPase or cathepsin-K, and in signaling factors, Src or TRAF-6, which were shown not to be significantly altered in gl osteoclasts. Thus, independently of a deficiency in V-ATPase, Src, cathepsin-K, and TRAF-6, the gl mutation results in increased number of osteoclasts, characterized by a disrupted cytoskeleton and an underdeveloped ruffled border.

Very early-onset bulimia nervosa: report of two cases.

Bulimia nervosa is very rare in children below the age of 14 years, and no reliable reports of prepubertal bulimia nervosa have been published. We describe two cases of early-onset bulimia nervosa who presented before the age of 14 years, and with premenarchal onset in one patient. Both girls demonstrated high levels of the risk factors known to play a part in the etiology of bulimia nervosa. Implications of these cases regarding the etiology and occurrence of bulimia nervosa in younger adolescents are discussed.