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Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.

Flow cytometric analysis of abnormal lymphocyte populations in chronic lymphocytic leukemia (CLL) has been widely reported to show weak expression of surface immunoglobulin (sIg). The international scoring system to help discriminate between CLL and other B-cell lymphoproliferative disorders lists this as the first of 5 criteria worth 1 point each. In the present study, 30 cases of CLL were studied for surface and cytoplasmic Ig expression. 23 of these 30 (76.7%) cases were positive for sIg. Of these 23, 14 cases (60.9%) showed moderate to bright sIg expression. All of these 23 cases were positive for CD5 and CD23; all were negative for CD10 and only 6 (26.1%) were positive for FMC7. 27 of 30 (90.0%) cases expressed cytoplasmic immunoglobulin (cIg) compared to 5% reported by others. This shows that cytoplasmic Ig occurs in a much greater percentage of cases than reported previously. 23 of 30 (76.7%) cases showed positivity for both surface and cytoplasmic Ig, with 15 showing kappa light chain restriction and 8 showing lambda light chain restriction. Six expressed cytoplasmic Ig only, with 4 showing kappa light chain restriction and 2 showing lambda light chain restriction. One case expressed neither cytoplasmic nor surface Ig. CD38 positivity portends a worse prognosis. Of the 29 cases tested for CD38, 13 (44.8%) were positive. Of these 13 cases, 12 were in the surface Ig/cytoplasmic Ig+ group and 1 in the cytoplasmic Ig+ group only. Also, of the 23 cases tested for CD22 expression, 16 (69.6%) were positive. These data question the use of both "weak" surface Ig expression and lack of CD22 expression as valid scoring criteria for CLL.

We describe a case of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infection leading to bilateral cavernous sinus thrombosis (CST) and subsequent left eye blindness in a previously healthy, immunocompetent woman. A secondary objective is to document all published cases of MRSA induced CST.To identify all relevant publications on MRSA-induced CST in adults.Seven publications were included in this review describing patients age 19 or older. Together, with the case included in this publication, a total of 8 cases of MRSA induced CST have been documented since 2003. Of interest, to our knowledge this is the first reported case of CA-MRSA CST temporally associated with nasal H1N1 vaccination.In selecting empiric antibiotic coverage for septic CST, the practitioner should use antibiotics that are active against CA-MRSA to help prevent morbidity and mortality.

The prognostic significance of selected markers of leukemic cells is well known. CD7 and CD56 expression at diagnosis has been associated with low remission rates and biological aggressiveness in a significant proportion of acute leukemias. Among 46 patients with acute myeloid leukemia, we found CD7 expression in 15 cases (32.6%) and CD56 positivity in 10 patients (21.7%). Six of these myeloid leukemia cases (13%) showed expression of both CD7 and CD56. Four of 46 (8.7%) patients expressed CD79a. Among the 10 that were acute myeloblastic leukemia, 8 expressed CD7, 4 expressed CD56, and 4 were positive for CD79a. Thus, these markers were expressed early in hemopoietic ontogeny in the lesser-differentiated acute myeloid leukemia subtypes, including FAB M0, M1, and M2. Whereas CD7 and CD56 were each positive in 4 cases of acute myelomonocytic leukemia (FAB M4 subtype), there was no CD79a expression in the M4 cases. CD7 is expressed by mature T cells, NK cells, and an immature myeloid cell subset. NK cells and a T cell subset express CD56. By contrast, CD79a is a B cell marker that is assigned a high score of 2.0 in the differentiation of acute leukemias of ambiguous lineage in the WHO classification. The aberrant expression of CD7, CD56, and CD79a, representing the capacity of these leukemias for trilineal expression of leukocyte differentiation antigens, portends a poor prognosis.