Two females with mutations in USP9X highlight the variable expressivity of the intellectual disability syndrome.

The genetic causes of intellectual disability (ID) are heterogeneous and include both chromosomal and monogenic etiologies. The X-chromosome is known to contain many ID-related genes and males show a marked predominance for intellectual disability. Here we report two females with syndromic intellectual disability. The first individual was relatively mild in her presentation with mild-moderate intellectual disability, hydronephrosis and altered pigmentation along the lines of Blaschko without additional congenital anomalies. A second female presented shortly after birth with dysmorphic facial features, post-axial polydactyly and, on follow-up assessment, demonstrated moderate intellectual disability. Chromosomal studies for Individual 1 identified an X-chromosome deletion due to a de novo pericentric inversion; the inversion breakpoint was associated with deletion of the 5'UTR of the USP9X, a gene which has been implicated in a syndromic intellectual disability affecting females. The second individual had a de novo frameshift mutation detected by whole-exome sequencing that was predicted to be deleterious, NM_001039590.2 (USP9X): c.4104_4105del (p.(Arg1368Serfs*2)). Haploinsufficiency of USP9X in females has been associated with ID and congenital malformations that include heart defects, scoliosis, dental abnormalities, anal atresia, polydactyly, Dandy Walker malformation and hypoplastic corpus callosum. The extent of the congenital malformations observed in Individual 1 was less striking than Individual 2 and other individuals previously reported in the literature, and suggests that USP9X mutations in females can have a wider spectrum of presentation than previously appreciated.

Temporal stability of the Minnesota Multiphasic Personality Inventory (MMPI) in patients undergoing lumbar fusion: a poor predictor of surgical outcome.

In this prospective study, the Minnesota Multiphasic Personality Inventory (MMPI) was administered to patients before and after lumbar spines fusion to investigate the stability of MMPI scores after surgical intervention and to attempt to correlate MMPI scale scores with outcome data. Sixty-eight patients were included. Testing was performed before surgery and at a mean of 1.5 years after surgery. Clinical outcome ratings were assigned by using criteria of pain relief and analgesic use. In addition, demographic variables known to affect outcome were analyzed. Sixty percent of the patients had a successful clinical outcome. Positive outcome correlated with the demographic factors of occupation (homemaker) and solid fusion. MMPI scales were stable across time, with no difference between groups. Independent t tests were used to study preoperative MMPI scores with respect to clinical outcome. Unsatisfactory outcomes were associated with higher scores on scales 1, 3, and 10 before surgery. Postoperative testing revealed significant outcome correlations--higher scores on scales 1, 2, 3, 5, 7, and 8 associated with an unsatisfactory outcome. However, discriminant function analysis of preoperative MMPI data was able to classify outcomes correctly in only 58.8% of the cases. The utility of the MMPI as a predictor of outcome after surgical intervention is quite limited. Use of group data and testing before and after surgery does not appear to influence this conclusion. Although the scores as a group were stable across time, the amount of variance in outcome that could not be accounted for by using MMPI scales as predictors was unacceptably large.

Mandibular elongation by bone distraction: treatment for mandibular hypoplasia with Robin sequence.

Robin sequence is the combination of micrognathia (small jaw), retrognathia (posterior displacement of the chin) and glossoptosis (falling backward of the tongue) in newborns, and is often found in combination with clefting of the palate. Mandibular elongation by bone distraction, described in this article, is one treatment for mandibular hypoplasia with Robin sequence.

The effectiveness of the cervical halo: open versus closed ring. A preliminary report.

The halo cervical orthosis has proven extremely effective in stabilizing the spine, both non-operatively and as a supplement to operative procedures. Current designs of the available halo utilize either a closed or an open stabilizing ring. Twenty-four patients with various indications for halo application are reviewed. Eleven were treated with a closed ring apparatus (Ace Medical, Los Angeles, California), and thirteen with an open ring device (Bremer, Inc, Jacksonville, Florida). X-rays of the treated patients were compared by group, and patients were interviewed regarding their complaints while wearing the halo. Rates of complication were compared. Results showed no significant differences between radiographs (kyphosis or translation) throughout the follow-up period. Patients experienced a significantly higher incidence of halo-associated pain in the open group. Otherwise, there were no statistical differences in the complication rates of either device. Whether or not the higher incidence of pain in the open group is related to decreased device rigidity is unknown. The open design may theoretically permit bending and opening of the ring to occur, the so-called 'wishbone' effect. Based on these data, it cannot be determined whether the advantages of the open ring--ease of application--are offset by this potential disadvantage. Clearly, a larger, randomized prospective study is required to investigate this.

Watson syndrome: is it a subtype of type 1 neurofibromatosis?

Over 20 years ago, Watson described three families with a condition characterised by pulmonary valvular stenosis, café au lait patches, and dull intelligence. Short stature is an additional feature of this autosomal dominant condition. A fourth family with Watson syndrome has since been reported. We have had the opportunity to review members of three of these four families. The clinical phenotype of Watson syndrome has been expanded to include relative macrocephaly and Lisch nodules in the majority of affected subjects, and neurofibromas in one-third of family members. Because the additional clinical findings enhance the similarity between Watson syndrome and neurofibromatosis 1, molecular linkage studies have been performed using probes flanking the NF1 gene on chromosome 17. Probe HHH202 showed the tightest linkage to Watson syndrome with a maximum lod score of 3.59 at phi = 0.0 (95% confidence limits of phi = 0.0-0.15). This suggests either that Watson syndrome and neurofibromatosis 1 are allelic, or that there is a series of contiguous genes for pulmonary stenosis, neurocutaneous anomalies, short stature, and mental retardation on 17q.

A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia.

Malignant hyperthermia (MH) is currently diagnosed by the caffeine-halothane contracture (CHC) test. In a previous study, this test was used to establish linkage between the human gene for MH susceptibility and the ryanodine receptor (RYR) gene. The current study extends the genetic linkage analysis to a large French-Canadian kindred. In this family, genetic linkage between RYR and MH genes was not demonstrable using the currently recommended limits of normal for the CHC test in the identification of MH-susceptible individuals. With CHC test threshold limits below those currently recommended, however, complete linkage between the RYR and MH genes was seen. Comparisons of CHC test results with genetic linkage studies will increase the diagnostic accuracy of both tests as well as generate new insights into the biology of MH.

DNA polymorphism and linkage disequilibrium within the apolipoprotein CII locus on human chromosome 19.

The gene for human apolipoprotein CII (APOCII) is located on the proximal long arm of chromosome 19. It has been established as a closely linked marker for myotonic dystrophy (DM), the most common form of adult muscular dystrophy. In the present linkage study, we have analysed 6 APOCII RFLPs in 213 haplotypes: TaqI, 3.8/3.5 kb; BgII, 12.0/9.0 kb; BanI, 2.5/1.6 kb; BamHI, 6.0/4.9 kb; NcoI, 14.5/11.5 kb, and AvaII, 0.6/0.4 kb. The polymorphic enzyme sites were determined to be present at the following frequencies: TaqI, 0.43; BglI, 0.51; BanI, 0.25; BamHI, 0.99; NcoI, 0.51, and AvaII, 0.52. Ordering of the polymorphic sites, 5'----3', has been determined to be (NcoI-BglI)-AvaII-BanI-TaqI. Significant disequilibrium was seen between 5 of the APOCII RFLPs.