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The Journal of Craniofacial Surgery May 2017Tracheal cartilaginous sleeve (TCS) is a rare and previously unrecognized source of morbidity and mortality in patients with certain craniosynostosis syndromes. There is...
Tracheal cartilaginous sleeve (TCS) is a rare and previously unrecognized source of morbidity and mortality in patients with certain craniosynostosis syndromes. There is a paucity of reporting on this airway anomaly, and the true incidence of TCS is largely unknown. The purpose of this study was to investigate the incidence of TCS among patients with syndromic craniosynostosis at our institution. Patients with syndromic craniosynostosis who underwent direct bronchoscopy and laryngoscopy were evaluated retrospectively by pediatric otolaryngologists for the presence of TCS and associated anomalies. Among patients with a diagnosis of syndromic craniosynostosis in our craniofacial database, 10 (37%) were found to have previous direct bronchoscopy and laryngoscopy reports. Of these 10 patients, 2 had Crouzon syndrome, 3 had Pfeiffer syndrome, 3 had Apert syndrome, 1 had Muenke syndrome, and 1 had Antley-Bixler syndrome. Eighty percent (8/10) of these patients were found to have some evidence of TCS. The most commonly observed associated findings included the following: tracheostomy dependency (7/10; 70%), hearing loss (6/10; 60%), obstructive sleep apnea (5/10; 50%), cervical spine anomalies (5/10; 50%), developmental delay (5/10; 50%), and enlarged cerebral ventricles (4/10; 40%). Larger multicenter studies are required to further characterize this airway anomaly and its impact on this patient population. Our results confirm the importance of thorough airway evaluation at initial presentation and the need for validated screening protocols.
Topics: Abnormalities, Multiple; Cartilage; Child; Child, Preschool; Craniosynostoses; Female; Humans; Male; Morbidity; Retrospective Studies; Sleep Apnea, Obstructive; Survival Rate; Trachea; Tracheal Diseases; Tracheostomy; United States
PubMed: 28468151
DOI: 10.1097/SCS.0000000000003489 -
Journal of Genetic Counseling Oct 2017
PubMed: 28432536
DOI: 10.1007/s10897-017-0103-x -
Journal of Genetic Counseling Oct 2017Muenke syndrome constitutes the most common syndromic form of craniosynostosis, occurring in 1 in 30,000 live births. The phenotype is variable, ranging from no clinical...
Muenke syndrome constitutes the most common syndromic form of craniosynostosis, occurring in 1 in 30,000 live births. The phenotype is variable, ranging from no clinical findings to complex presentation. Facilitating reproductive decision making for couples at genetic risk of having a child with Muenke syndrome is an important aspect of genetic counselling. Prenatal genetic testing for Muenke syndrome is accurate; however the value of testing is uncertain with a variable phenotype. The purpose of this study was to explore attitudes towards prenatal testing in couples where one partner had tested positive for the Muenke mutation. We used a qualitative approach based on thematic analysis and collected data using individual semi-structured interviews with eight parents. Five key themes were: The Muenke journey; Impact and knowledge of diagnosis; Knowledge and attitude to prenatal testing; Stigma and sharing of information; and Information retention. Knowledge of Muenke syndrome and prenatal testing was poor. Genetic information was provided when treatment of their affected child was their paramount concern. Couples reported not sharing genetic information with family due to fear of stigmatisation. Couples cannot make reproductive decisions if lacking appropriate understanding of the choices: timely genetic counselling regarding prenatal testing is needed when relevant to them.
Topics: Adult; Attitude; Craniosynostoses; Decision Making; Female; Genetic Counseling; Genetic Testing; Humans; Male; Parents; Phenotype; Prenatal Diagnosis; Qualitative Research; Syndrome
PubMed: 28332077
DOI: 10.1007/s10897-017-0094-7 -
Facial Plastic Surgery Clinics of North... Nov 2016Syndromic craniosynostosis affects up to 1:30,000 live births with characteristic craniofacial growth restrictions, deformities, and other associated abnormalities, such... (Review)
Review
Syndromic craniosynostosis affects up to 1:30,000 live births with characteristic craniofacial growth restrictions, deformities, and other associated abnormalities, such as carpal-pedal anomalies and cognitive function impairment. More than 150 syndromes are associated with craniosynostosis. This article describes some commonalities and distinguishing features and management of syndromic synostosis. Also addressed is secondary synostosis, which is often found in syndromic children with problems related to microcephaly, hydrocephalus, or shunt-induced craniosynostosis, although pathophysiologically and genetically different. The importance of obtaining a thorough history and a complete physical and examination is highlighted. Adjuvant testing and multidisciplinary management are discussed.
Topics: Craniofacial Dysostosis; Craniosynostoses; Humans; Osteogenesis, Distraction; Syndrome
PubMed: 27712819
DOI: 10.1016/j.fsc.2016.06.008 -
American Journal of Medical Genetics.... Jan 2017Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients...
Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients with Pfeiffer syndrome type 2 (PS-2), one patient with Jackson-Weiss syndrome (JWS), and two patients (sisters) with Muenke syndrome (MS). FGFR2 and FGFR3 mutations were identified in 10 of the 11 patients. Notably, we found a novel FGFR2 p.Asn549Thr mutation in a patient with CS, and a novel FGFR2 p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an FGFR2-related PS-variant). We also identified an FGFR2 p.Ser252Leu mutation in a phenotypically normal father of a daughter with CS, and an FGFR3 p.Pro250Arg mutation in a mildly macrocephalic father of sisters with MS. These findings, together with previous data, imply that the same FGFR2 mutations can be associated with a wide range of phenotypes including clinically different forms of syndromic craniosynostosis and apparently normal phenotype, depending on other (epi)genetic and environmental factors. Thus, genetic studies are recommended not only for obviously affected individuals but also for family members with apparently normal phenotype or non-specific subtle abnormal phenotype, to allow for pertinent genetic counseling. © 2016 Wiley Periodicals, Inc.
Topics: Alleles; Amino Acid Substitution; Asian People; Craniosynostoses; DNA Mutational Analysis; Diagnostic Imaging; Facies; Female; Genetic Association Studies; Genotype; Humans; Infant; Infant, Newborn; Japan; Male; Mutation; Phenotype; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2; Receptor, Fibroblast Growth Factor, Type 3; Syndrome
PubMed: 27683237
DOI: 10.1002/ajmg.a.37992 -
American Journal of Medical Genetics.... Dec 2016Muenke syndrome (MS) is an autosomal dominant coronal craniosynostosis syndrome with variable extracranial anomalies. We studied 56 unrelated patients with non-syndromic...
Muenke syndrome (MS) is an autosomal dominant coronal craniosynostosis syndrome with variable extracranial anomalies. We studied 56 unrelated patients with non-syndromic uni- or bicoronal craniosynostosi to identify the frequency and clinical characteristics of MS in a cohort of Mexican childrens. The FGFR3 pathogenic variation p.Pro250Arg responsible for MS was characterized in all probands by PCR-restriction assay; available first-degree relatives (15 parents, 5 siblings) of the confirmed p.Pro250Arg carriers were also tested. All heterozygotes for p.Pro250Arg underwent clinical and audiologic assessment, as well as X-ray evaluations of hands and feet. Eight of 56 probands (14%) were found to carry the p.Pro250Arg variant and half of them were familial cases. Four p.Pro250Arg heterozygous familial members had been considered unaffected before the molecular testing. In one MS family, hydrocephalus without craniosynostosis, was documented as the only clinical manifestation in a previously undetected heterozygous male sibling. Hydrocephalus without craniosynostosis in a patient with the p.Pro250Arg variant suggests that some patients with MS might present only this manifestation; to our knowledge, hydrocephalus has not been described as isolated feature in MS, so we propose to consider this feature as an expansion of the MS phenotype rather than an unrelated finding. Our data also reinforce the notion that molecular testing of FGFR3 must be included in the diagnostic approach of coronal craniosynostosis. This will allow accurate genetic counseling and optimal management of MS, which might otherwise go undiagnosed because of mild manifestations and wide variability of expression. © 2016 Wiley Periodicals, Inc.
Topics: Craniosynostoses; Female; Genetic Counseling; Heterozygote; Humans; Hydrocephalus; Male; Mutation; Pedigree; Phenotype; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 27568649
DOI: 10.1002/ajmg.a.37951 -
Journal of Plastic, Reconstructive &... Sep 2016Max Muenke included midface hypoplasia as part of the clinical syndrome caused by the Pro250Arg FGFR3 mutation that now bears his name. Murine models have demonstrated... (Review)
Review
BACKGROUND
Max Muenke included midface hypoplasia as part of the clinical syndrome caused by the Pro250Arg FGFR3 mutation that now bears his name. Murine models have demonstrated midface hypoplasia in homozygous recessive mice only, with heterozygotes having normal midfaces; as the majority of humans with the syndrome are heterozygotes, we investigated the incidence of midface hypoplasia in our institution's clinical cohort.
METHODS
We retrospectively reviewed all patients with a genetic and clinical diagnosis of Muenke syndrome from 1990 to 2014. Review of clinical records and photographs included skeletal Angle Class, dental occlusion, and incidence of orthognathic intervention. Cephalometric evaluation of our patients was compared to the Eastman Standard Values.
RESULTS
18 patients met inclusion criteria - 7 females and 11 males, with average follow-up of 11.2 years (1.0-23.1). Cephalometric analysis revealed an average sella-nasion-A point angle (SNA) of 82.5 (67.8-88.8) and an average sella-nasion-B point angle (SNB) of 77.9 (59.6-84.1). The SNA of our cohort was found to be significantly different from the Eastman Standards (p = 0.017); subgroup analysis revealed that this was due to the mixed dentition group which had a higher than average SNA. 12 patients were noted to be in Class I occlusion, 4 in Class II malocclusion, and 2 in Class III malocclusion. Only one patient (6%) underwent orthognathic surgery for Class III malocclusion.
CONCLUSIONS
While a part of the original description of Muenke syndrome, clinically significant midface hypoplasia is not a common feature. This data is important, as it allows more accurate counseling of patients and families.
LEVEL OF EVIDENCE
III.
Topics: Cephalometry; Craniosynostoses; Face; Female; Humans; Male; Severity of Illness Index
PubMed: 27449747
DOI: 10.1016/j.bjps.2016.06.017 -
International Journal of Pediatric... Jun 2016To assess the audiological profile in a cohort of children affected by syndromic craniosynostosis.
OBJECTIVE
To assess the audiological profile in a cohort of children affected by syndromic craniosynostosis.
METHODS
Eleven children with Apert syndrome (n=4), Saethre-Chotzen syndrome (n=3), Muenke syndrome (n=2), Crouzon syndrome (n=1) and Pfeiffer syndrome type 1 (n=1) were submitted to a complete audiologic evaluation including otoscopy, pure-tone audiometry, tympanometry and acoustic reflex testing, ABR, otoacustic emissions, temporal bone High Resolution CT (HRCT) scan. The main outcome measures were prevalence, type and severity of hearing loss, prevalence of chronic otitis media, correlation with the time of first surgical correction.
RESULTS
Seven of 11 patients (64%) presented hearing loss (HL), conductive in 3/7 patients (43%) and mixed in 4/7 (57%). No patients showed a purely sensorineural HL. All hearing impaired patients displayed middle ear disorders: the patients with conductive HL had otitis media with effusion (OME) and 3/4 patients with mixed HL showed tympanic alterations or cholesteatoma. A bilateral vestibular aqueduct enlargement was detected by HRCT scan in one normal hearing patient. The ABRs resulted normal in all cases.
CONCLUSION
Our study confirms the high prevalence of otologic diseases in such patients. In contrast with previous studies, middle ear disorders were responsible for the hearing impairment also in patients with mixed HL due to secondary inner ear damage. These findings restate the necessity of a close audiologic follow-up. We did not detect the specific ABR abnormalities previously reported, possibly because of an early correction of the cranial vault malformations.
Topics: Acrocephalosyndactylia; Adolescent; Child; Child, Preschool; Chronic Disease; Cohort Studies; Craniofacial Dysostosis; Craniosynostoses; Female; Hearing Loss; Hearing Tests; Humans; Male; Otitis Media; Otoscopy; Prevalence; Tomography, X-Ray Computed
PubMed: 27240504
DOI: 10.1016/j.ijporl.2016.03.038 -
Journal of Korean Neurosurgical Society May 2016Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various... (Review)
Review
Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.
PubMed: 27226847
DOI: 10.3340/jkns.2016.59.3.187 -
Anales de Pediatria (Barcelona, Spain :... Jul 2017
Topics: Craniosynostoses; Humans; Infant; Phenotype
PubMed: 27106663
DOI: 10.1016/j.anpedi.2016.02.005