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Muenke syndrome: Medical and surgical comorbidities and long-term management.

ABSTRACT: Muenke syndrome (MIM #602849), the most common syndromic craniosynostosis, results from the recurrent pathogenic p.P250R variant in FGFR3. Affected patients exhibit wide phenotypic variability. Common features include coronal craniosynostosis, hearing loss, carpal and tarsal anomalies, and developmental/behavioral issues. Our study examined the phenotypic findings, medical management, and surgical outcomes in a cohort of 26 probands with Muenke syndrome identified at the Children's Hospital of Philadelphia. All probands had craniosynostosis; 69.7% had bicoronal synostosis only, or bicoronal and additional suture synostosis. Three male patients had autism spectrum disorder. Recurrent ear infections were the most common comorbidity, and myringotomy tube placement the most common extracranial surgical procedure. Most patients (76%) required only one fronto-orbital advancement. de novo mutations were confirmed in 33% of the families in which proband and both parents were genetically tested, while in the remaining 66% one of the parents was a mutation carrier. In affected parents, 40% had craniosynostosis, including 71% of mothers and 13% of fathers. We additionally analyzed the medical resource utilization of probands with Muenke syndrome. To our knowledge, these data represent the first comprehensive examination of long-term management in a large cohort of patients with Muenke syndrome. Our study adds valuable information regarding neuropsychiatric and medical comorbidities, and highlights findings in affected relatives.

SUBMITTER: Murali CN

PROVIDER: S-EPMC6959001 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Muenke syndrome: Medical and surgical comorbidities and long-term management.

Murali Chaya N CN McDonald-McGinn Donna M DM Wenger Tara Lynn TL McDougall Carey C Stroup Bridget M BM Sheppard Sarah E SE Taylor Jesse J Bartlett Scott P SP Bhoj Elizabeth J EJ Zackai Elaine H EH Santani Avni A

American journal of medical genetics. Part A 20190520 8

Muenke syndrome (MIM #602849), the most common syndromic craniosynostosis, results from the recurrent pathogenic p.P250R variant in FGFR3. Affected patients exhibit wide phenotypic variability. Common features include coronal craniosynostosis, hearing loss, carpal and tarsal anomalies, and developmental/behavioral issues. Our study examined the phenotypic findings, medical management, and surgical outcomes in a cohort of 26 probands with Muenke syndrome identified at the Children's Hospital of P ...[more]

PMID: 31111620

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Project description:ImportanceThe association of bariatric surgery and specialized medical obesity treatment with beneficial and detrimental outcomes remains uncertain.ObjectiveTo compare changes in obesity-related comorbidities in patients with severe obesity (body mass index ≥40 or ≥35 and at least 1 comorbidity) undergoing bariatric surgery or specialized medical treatment.Design, setting, and participantsCohort study with baseline data of exposures from November 2005 through July 2010 and follow-up data from 2006 until death or through December 2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway. Consecutive treatment-seeking adult patients (n = 2109) with severe obesity assessed (221 patients excluded and 1888 patients included).ExposuresBariatric surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956) including individual or group-based lifestyle intervention programs.Main outcomes and measuresPrimary outcomes included remission and new onset of hypertension based on drugs dispensed according to the Norwegian Prescription Database. Prespecified secondary outcomes included changes in comorbidities. Adverse events included complications retrieved from the Norwegian Patient Registry and a local laboratory database.ResultsAmong 1888 patients included in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean [SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years [range, 0.2-10.1]). Surgically treated patients had a greater likelihood of remission and lesser likelihood for new onset of hypertension (remission: absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%-23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%, RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9 [95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD, 2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids: AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]). Surgical patients had a greater risk for undergoing at least 1 additional gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%-18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin levels was significantly greater in the surgical group (26% vs 12%, P < .001).Conclusions and relevanceAmong patients with severe obesity followed up for a median of 6.5 years, bariatric surgery compared with medical treatment was associated with a clinically important increased risk for complications, as well as lower risks of obesity-related comorbidities. The risk for complications should be considered in the decision-making process.

Project description:ImportanceRandomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration.ObjectiveTo determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes.Design, setting, and participantsARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022.InterventionParticipants were originally randomized to undergo either medical/lifestyle management or 1 of the following 3 bariatric surgical procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding.Main outcome and measuresThe primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 7 years for all participants. Data are reported for up to 12 years.ResultsA total of 262 of 305 eligible participants (86%) enrolled in long-term follow-up for this pooled analysis. The mean (SD) age of participants was 49.9 (8.3) years, mean (SD) body mass index was 36.4 (3.5), 68.3% were women, 31% were Black, and 67.2% were White. During follow-up, 25% of participants randomized to undergo medical/lifestyle management underwent bariatric surgery. The median follow-up was 11 years. At 7 years, HbA1c decreased by 0.2% (95% CI, -0.5% to 0.2%), from a baseline of 8.2%, in the medical/lifestyle group and by 1.6% (95% CI, -1.8% to -1.3%), from a baseline of 8.7%, in the bariatric surgery group. The between-group difference was -1.4% (95% CI, -1.8% to -1.0%; P < .001) at 7 years and -1.1% (95% CI, -1.7% to -0.5%; P = .002) at 12 years. Fewer antidiabetes medications were used in the bariatric surgery group. Diabetes remission was greater after bariatric surgery (6.2% in the medical/lifestyle group vs 18.2% in the bariatric surgery group; P = .02) at 7 years and at 12 years (0.0% in the medical/lifestyle group vs 12.7% in the bariatric surgery group; P < .001). There were 4 deaths (2.2%), 2 in each group, and no differences in major cardiovascular adverse events. Anemia, fractures, and gastrointestinal adverse events were more common after bariatric surgery.Conclusion and relevanceAfter 7 to 12 years of follow-up, individuals originally randomized to undergo bariatric surgery compared with medical/lifestyle intervention had superior glycemic control with less diabetes medication use and higher rates of diabetes remission.Trial registrationClinicalTrials.gov Identifier: NCT02328599.

Dataset Information

Muenke syndrome: Medical and surgical comorbidities and long-term management.

Publications

Muenke syndrome: Medical and surgical comorbidities and long-term management.

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