Hospital Rankings and Health Equity.

This Viewpoint examines US News & World Report's approach to evaluating and publicly reporting hospital performance in various aspects of health equity as well as describes several novel equity measures published as part of its "Best Hospitals" rankings program.

Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic challenges, and unmet milestones.

In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research. Furthermore, the FDA approved Hedgehog pathway inhibitors Vismodegib and Sonidegib designed for advanced basal cell carcinoma have opened a new door for treatment that may ultimately decrease the number of surgeries for a patient with Gorlin syndrome. The role of these agents in syndromic odontogenic keratocyst has not been studied extensively, but one study found that hedgehog pathway inhibitors decrease the size of syndromic odontogenic keratocyst. Ideal surgical treatment that balances low recurrence rates with low impact on one's quality of life for syndromic odontogenic keratocyst is another unanswered question for oral and maxillofacial surgeons. Per survey studies, treatment options practiced for syndromic odontogenic keratocyst range from marsupialization to segmental osteotomy. Future studies performed should take a comprehensive long-term approach with at least three years of follow-up in order to determine the most appropriate treatment.

Otopalatodigital syndrome type 2 in a male infant: A case report with a novel sequence variation.

We report a male infant with typical clinical, pathological and radiological features of otopalatodigital syndrome type 2 (OPD 2) with a novel sequence variation in the FLNA gene. His clinical manifestations include typical craniofacial features, cleft palate, hearing impairment, omphalocele, bowing of the long bones, absent fibulae and digital abnormalities consistent with OPD 2. Two hemizygous sequence variations in the FLNA gene were identified. The variation c.5290G>A/p.Ala1764Thr has been previously reported in a patient with periventricular nodular heterotopia, but subsequently it has been reported as a polymorphism. The other variation c.613T>C/p.Cys205Arg detected in the proband has not been previously reported and our analysis indicates that this is a novel disease-causing mutation for OPD2.

Follow-up study of immune defects in patients with dysmorphic disorders.

BACKGROUND: In a previous study, we noted immunologic abnormalities in 46 (54.8%) of 84 individuals with dysmorphic disorders. OBJECTIVE: To reevaluate patients with dysmorphic disorders and immunologic abnormalities 2 to 3 years after an initial study to determine any changes in those abnormalities. METHODS: Information was gathered regarding significant infections during the previous 12 months. Blood samples were drawn for the immunologic tests that were previously performed (IgG, IgA, and IgM level determinations; complete blood cell count; and lymphocyte subset enumeration) and for determination of IgG subclasses and T-cell activation by CD69 expression. RESULTS: In the 21 patients available, 26 (63.4%) of the previously noted 41 low immunologic values were still present. In 5 patients, all previously noted immunologic abnormalities resolved. Of the 17 low values noted in 6 patients with Down syndrome, 12 (70.6%) were still present. Also, the 2 patients with Turner syndrome continued to have low IgA and IgM levels. Two patients had a low IgG4 level. A history of significant clinical infections within the previous 12 months was noted in 10 (58.8%) of 17 patients; 8 (47%) had current immune defects. There was a significantly lower T-cell response to staphylococcal enterotoxin B than in healthy controls. The T-lymphocyte activation response was low in 8 (38.1%) of the 21 patients. CONCLUSIONS: Our study revealed a high rate of immune defects in patients with dysmorphic disorders, both during the initial study and 2 to 3 years later, which may contribute to their increased susceptibility to infections. This association was most obvious in patients with Down syndrome and Turner syndrome. The findings should alert for early immunologic evaluation when such patients have infections.

Johanson-Blizzard syndrome: autopsy findings with special emphasis on hypopituitarism and review of the literature.

We present the 1st autopsy findings of a child who had Johanson-Blizzard syndrome (JBS) and hypopituitarism. The patient died of acute bronchopneumonia at the age of 4 years. The autopsy revealed a small undescended pituitary that contained a glial hamartoma and a small rim of adenohypopysial cells, which were minimally reactive immunohistologically only for growth hormone. We review the literature with regard to other cases of JBS and hypopituitarism and pituitary function. The need for evaluating pituitary function in all patients with JBS is stressed. At the time of his death, our patient had no clinical evidence of pancreatic exocrine deficiency, and the histology of the pancreas revealed a normal number of acini; however, the acinar cells had an immature appearance. The microlobules were separated by loose fibrous tissue, and there was extensive periductal fibrosis. The spectrum of the pathognomic feature of congenital pancreatic exocrine insufficiency in JBS is discussed.

Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8.

Trismus-pseudocamptodactyly syndrome (TPS) is a rare autosomal dominant distal arthrogryposis (DA) characterized by an inability to open the mouth fully (trismus) and an unusual camptodactyly of the fingers that is apparent only upon dorsiflexion of the wrist (i.e., pseudocamptodactyly). TPS is also known as Dutch-Kentucky syndrome because a Dutch founder mutation is presumed to be the origin of TPS cases in the Southeast US, including Kentucky. To date only a single mutation, p.R674Q, in MYH8 has been reported to cause TPS. Several individuals with this mutation also had a so-called "variant" of Carney complex, suggesting that the pathogenesis of TPS and Carney complex might be shared. We screened MYH8 in four TPS pedigrees, including the original Dutch family in which TPS was reported. All four TPS families shared the p.R674Q substitution. However, haplotype analysis revealed that this mutation has arisen independently in North American and European TPS pedigrees. None of the individuals with TPS studied had features of Carney complex, and p.R674Q was not found in 49 independent cases of Carney complex that were screened. Our findings show that distal arthrogryposis syndromes share a similar pathogenesis and are, in general, caused by disruption of the contractile complex of muscle.

Immune defects in subjects with dysmorphic disorders.

Patients with dysmorphic disorders seem to have frequent respiratory infections that may be attributed to associated anatomic or neurological abnormalities, but immune defects may contribute to their susceptibility to infections. We screened subjects with dysmorphic conditions for major hematologic, B-cell and T-cell defects. We studied 84 subjects with dysmorphic disorders: 29 with chromosomal disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic disorders. They were evaluated by physical examination; medical history suggestive of possible immune deficiency; complete blood count; serum immunoglobulin G (IgG), IgA, and IgM levels; and lymphocyte subsets. Low laboratory values (less than fifth percentile for age) were detected in 54.8%; was highest in the chromosomal disorder group (79.3%) followed by the single gene disorder group (55.6%) and was lowest in the unclassified dysmorphic disorder group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte subpopulations followed by IgG and IgA levels. None of the subjects had neutropenia or thrombocytopenia. History of significant recurrent infections was noted in five subjects, all of whom had abnormal laboratory values. The highest frequency of abnormal laboratory values was in Down syndrome followed by Turner syndrome and chromosome deletions. We concluded that patients with dysmorphic disorders, particularly those with chromosomal disorders, have a high frequency of various B-cell and T-cell defects that may be contributing to their susceptibility to infection. Studies are needed to further delineate the immunologic defects in that population and to investigate a possible genetic basis at the molecular level.