Velopharyngeal dysfunction and speech-related characteristics in craniofacial microsomia: a retrospective analysis of 223 patients.

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P. VPD was significantly more prevalent in CFM with CL/P than in CFM without CL/P (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.9-8.7; P < 0.001). Multivariate logistic regression showed a significant association between CL/P and VPD in CFM patients (OR 7.4, 95% CI 2.1-26.3; P = 0.002). The presence of VPD was not associated with sex, the laterality or severity of CFM. Speech problems related to VPD appeared to be similar among the different groups (CFM without CL/P, CFM with CL/P, CL/P without CFM). As 15.2% of all CFM patients and 8.5% of CFM patients without CL/P had VPD, it is proposed that all patients with CFM, with or without CL/P, should be assessed by a speech and language therapist for the potential risk of VPD.

Hearing impairment and ear anomalies in craniofacial microsomia: a systematic review.

The aim of this systematic review was to review the literature on hearing impairment and ear anomalies in patients with craniofacial microsomia and to determine their prevalence. Sixty-two records including 5122 patients were included. Ear anomalies were present in 52-100% of patients. The most reported external ear malformations were microtia, pre-auricular tags, and atresia of the external auditory canal. Ossicular anomalies were the most reported middle ear malformations, whereas the most reported inner ear malformations included oval window anomalies, cochlear anomalies, and anomalies of the semicircular canals. Hearing loss in general was reported in 29-100% of patients, which comprised conductive hearing loss, mixed hearing loss, and sensorineural hearing loss. Between 21% and 51% of patients used hearing aids, and 58% underwent a surgical intervention to improve hearing. The relationship between different phenotypes of craniofacial microsomia and the type and severity of hearing loss is mostly unclear. In conclusion, the high prevalence of ear and hearing anomalies in patients with craniofacial microsomia underlines the importance of audiological screening in order to facilitate individual treatment.

Ocular and adnexal anomalies in craniofacial microsomia: Type and prevalence in a multicentre cohort study.

The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development.

Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients.

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n=32) and cardiac (n=13) anomalies were most frequently seen, followed by reproductive system (n=11), central nervous system (n=7), and limb (n=7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001-2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.

Ocular and adnexal anomalies in craniofacial microsomia: a systematic review.

Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7-100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis and strabismus were the most reported type III anomalies, and irregular astigmatism was the most reported type IV ocular anomaly. Visual impairment in general was reported in 8-71.4% of patients, with severe visual impairment in 11.1-71.4% and amblyopia in 16.3%. This study provides a detailed overview of ocular anomalies in CFM and their prevalence. Furthermore, we propose a new classification to organize ocular anomalies into four clinically relevant subtypes. Finally, the high prevalence of ocular anomalies and visual impairment in this study suggests that CFM patients should undergo ophthalmological screening at least once during the sensitive period.

Extracraniofacial anomalies in craniofacial microsomia: retrospective analysis of 991 patients.

Craniofacial microsomia (CFM) is characterized by unilateral or bilateral underdevelopment of the facial structures arising from the first and second pharyngeal arches, but extracraniofacial anomalies may also be present. This retrospective study provides an overview of the prevalence, types, and characteristics of extracraniofacial anomalies in patients with CFM. All patients diagnosed with CFM seen at four craniofacial centres were included. The patient charts were reviewed and data on patient characteristics and extracraniofacial anomalies were extracted. Of the 991 patients included, 462 (47%) had extracraniofacial anomalies. The prevalence of extracraniofacial anomalies in the various tracts was as follows: vertebral 28%, central nervous system 11%, circulatory system 21%, respiratory tract 3%, gastrointestinal tract 9%, and urogenital tract 11%. Compared to patients without extracraniofacial anomalies, those with an extracraniofacial anomaly were at higher risk of having additional extracraniofacial anomalies in other tracts. The prevalence of extracraniofacial anomalies was greater in patients with bilateral CFM, a more severe mandibular deformity, or facial nerve or soft tissue deformity. Patients with CFM should be screened for extracraniofacial anomalies by physical examination with specific attention to the circulatory, renal, and neurological tracts. Diagnostically, electrocardiography, echocardiography, spine radiography, and renal ultrasound should be performed for patients at risk of extracraniofacial anomalies.

Central nervous system anomalies in craniofacial microsomia: a systematic review.

Extracraniofacial anomalies, including central nervous system (CNS) anomalies, may occur in craniofacial microsomia (CFM). This systematic review was performed to provide an overview of the literature on the prevalence and types of CNS anomalies and developmental disorders in CFM, in order to improve the recognition and possible treatment of these anomalies. A systematic search was conducted and data on the number of patients, patient characteristics, type and prevalence of CNS anomalies or developmental delay, and correlations between CFM and CNS anomalies were extracted. Sixteen papers were included; 11 of these described developmental disorders. The most common reported anomalies were neural tube defects, corpus callosum agenesis or hypoplasia, intracranial lipoma, Arnold-Chiari malformations, hydrocephaly, ventriculomegaly, and cerebral hypoplasia. The prevalence of CNS anomalies in CFM varied from 2% to 69%. The prevalence of developmental disorders, such as intellectual disability, language or speech developmental delay, and neuropsychomotor delay, varied from 8% to 73%. This study suggests that CNS anomalies and developmental disorders are seen in a substantial proportion of patients with CFM. Further research should focus on determining which features of CFM are correlated with CNS anomalies to allow adequate screening and timely care.

Anticoagulation withdrawal in antiphospholipid syndrome: a retrospective matched-control study.

Background/Purpose Long-term anticoagulation is the standard treatment for thrombotic antiphospholipid syndrome (APS). However, in daily practice, the question of withdrawing anticoagulation may arise, without any evidence-based recommendations. This study aimed to assess outcomes in APS patients after anticoagulation withdrawal. Methods Thrombotic APS patients followed in our centre, whose anticoagulation was withdrawn after APS diagnosis, were retrospectively selected, and were match-controlled with patients under anticoagulation, based on sex, age, APS clinical phenotype and disease duration. Results Thirty cases with anticoagulation withdrawal were included. Median follow-up was 51 months (12-124). The risk of thrombotic relapse was higher in cases compared to controls (7.3% versus 1.5% patient-year ( p = 0.01); hazard ratio 4.8; 95% confidence interval (1.4-16.7)). Male gender, anti-ß2GP1 and triple positivity at inclusion were predictive factors for thrombotic relapse. Conversely, aspirin prescription was a protective factor against relapses. Persistence of LA, anti-ß2GP1 and triple positivity over time were associated with a higher risk of thrombosis and aPL disappearance with a lower risk. Conclusion In our study, anticoagulation withdrawal was associated with an increased risk of thrombotic relapse. Our findings emphasize the influence of anti-ß2GP1 and triple positivity persistence over time on the risk of relapse and the benefit of aspirin prescription when anticoagulation has been withdrawn.

Vertebral anomalies in craniofacial microsomia: a retrospective analysis of 991 patients.

Craniofacial microsomia (CFM) is characterized by an underdevelopment of the facial structures arising from the first and second branchial arches, but extracraniofacial anomalies such as vertebral anomalies may be present. This retrospective study was performed to determine the prevalence and types of vertebral anomalies and the association with other extracraniofacial anomalies in patients with CFM. The charts of all patients diagnosed with CFM seen in four craniofacial centres were reviewed for the presence of vertebral anomalies, symptoms, extracraniofacial anomalies, and the OMENS classification including the Pruzansky-Kaban type of mandibular deformity. A total of 991 patients were included and 28% of the patients had vertebral anomalies. The most common vertebral anomalies included scoliosis, block vertebrae, and hemivertebrae. Only 44% of the patients with vertebral anomalies had clinical symptoms; torticollis, back or neck pain, and limited neck movement were the most frequently seen. The prevalence of vertebral anomalies was greater in patients with bilateral CFM and in patients with a more severe mandibular deformity, and/or orbit, facial nerve, and/or soft tissue involvement. Patients with vertebral anomalies had significantly more extracraniofacial anomalies than patients without vertebral anomalies. Therefore, patients with vertebral anomalies should undergo cardiac, renal, and neurological evaluation.

Cochlear implantation in Malawi: report of the first four cases.

OBJECTIVE: This paper reports on the first four cochlear implant cases in Malawi. CASE REPORTS: Three patients were deafened from infectious diseases and one from an unknown cause. They all had post-lingual deafness. Six months after the last implant, they are all progressing well. CONCLUSION: Despite significant practical difficulties, it has proved possible, with the right support, to carry out cochlear implantation in one of the world's poorest countries. The project has also raised awareness of deafness in Malawi and highlighted significant public health issues relating to the aetiology of deafness in developing countries.

Vertebral anomalies in craniofacial microsomia: a systematic review.

Craniofacial microsomia (CFM) is characterized by a heterogeneous underdevelopment of the facial structures arising from the first and second branchial arches, but extracraniofacial malformations such as vertebral anomalies also occur. This systematic review provides an overview of the literature on the types and prevalence of vertebral anomalies found in patients with CFM. A systematic search was conducted. Data on the number of patients, patient characteristics, types and prevalence of vertebral anomalies, and other associations between CFM and vertebral anomalies were extracted from the articles identified. Thirty-one articles were included. Seventeen articles described both the prevalence and types of vertebral anomalies in CFM, five articles described solely the types of vertebral anomalies in CFM, and nine articles reported solely the prevalence of vertebral anomalies in CFM. The vertebral anomalies most often reported in CFM are hemivertebrae, block vertebrae, scoliosis/kyphoscoliosis, and spina bifida. These anomalies are mostly present in the cervical and thoracic spine and ribs. The reported prevalence of vertebral anomalies in CFM varies from 8% to 79%. To diagnose vertebral anomalies early in patients with CFM, further research should focus on determining which patients with CFM are at risk of vertebral anomalies.

Obstructive sleep apnoea in craniofacial microsomia: analysis of 755 patients.

A retrospective cohort study was set up to analyse the prevalence and treatment of obstructive sleep apnoea (OSA) in relation to the severity of the deformity in patients with craniofacial microsomia (CFM). This study included a population of 755 patients with CFM from three craniofacial centres. Medical charts were reviewed for severity of the deformity, types of breathing difficulty, age at which breathing difficulty first presented, treatment for OSA, and treatment outcome. In total, 133 patients (17.6%) were diagnosed with OSA. Patients with Pruzansky IIB/III classification or bilateral craniofacial microsomia were significantly more often diagnosed with OSA than unilaterally affected patients of Pruzansky I/IIA classification. The initial treatment of OSA consisted of adenotonsillectomy, tracheotomy, or non-invasive positive pressure ventilation. Thirty-seven patients received more than one treatment (range 1-3). In this study, the prevalence of OSA in patients with CFM was higher than the prevalence in the healthy population described in the literature. Although several treatment modalities are available for the treatment of OSA in patients with CFM, treatment should be individualized and based on clinical symptoms, the severity of the deformity, and comorbidities.

Agreement between factor XIII activity and antigen assays in measurement of factor XIII: A French multicenter study of 147 human plasma samples.

INTRODUCTION: Factor XIII (FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency (FXIIID) when activity is decreased. METHODS: The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay® FXIII reagent from Stago, for first-line measurement of FXIII antigen. Results were compared to those obtained with the Berichrom® FXIII chromogenic assay for measurement of FXIII activity. Of the 147 patient plasma samples, 138 were selected for analysis. RESULTS: The accuracy was very good, with intercenter reproducibility close to 7%. Five groups were defined on FXIII activity level (<5% (n = 5), 5%-30% (n = 23), 30%-60% (n = 17), 60%-120% (n = 69), above 120% (n = 24)), without statistical differences between activity and antigen levels (P value >0.05). Correlation of the K-Assay® with the Berichrom® FXIII activity results was excellent (r = 0.919). Good agreement was established by the Bland and Altman method, with a bias of +9.4% on all samples, and of -1.4% for FXIII levels lower than 30%. One patient with afibrinogenemia showed low levels of Berichrom® FXIII activity but normal antigen level and clot solubility as expected. CONCLUSIONS: The measurement of FXIII antigen using the K-Assay® is a reliable first-line tool for detection of FXIII deficiency when an activity assay is not available.

Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity.

Introduction The long-term risk of first thrombosis and benefit of prophylaxis in antiphospholipid antibody (aPL) carriers without history of thrombosis or obstetrical morbidity is poorly known. This study aimed to evaluate the long-term rate and risk factors associated with a first thrombosis in those patients. Patients and methods After a prior study ended in December 2005 and was already published, we extended the follow-up period of our cohort of aPL carriers. Results Ninety-eight of the 103 patients of the previous study were included. The annual first thrombosis rate was 2.3% per patient-year during a median of 13 years (6-17). None of the baseline characteristics was predictive of risk of first thrombosis, but persistent aPL over time were associated with an increased risk. The stronger association was found in triple aPL-positive carriers: OR 3.38 (95% CI: 1.24-9.22). Of note, conversely to our previous findings, no benefit of aspirin prophylaxis was observed. Conclusion The risk of first thrombosis in aPL carriers without history of thrombosis or obstetrical morbidity was significant, persisted linearly over time and was associated with persistent aPL. This risk was especially increased in triple aPL-positive carriers, in whom a close follow-up seems to be necessary. Nevertheless, the benefit of aspirin prophylaxis remained unclear.

Are there any additional mechanisms for haemolysis in HELLP syndrome?

HELLP syndrome is a microangiopathy that leads to severe maternal complications. The objective of this study was to identify any additional mechanisms that could have contributed to HELLP syndrome-induced haemolysis. This is a pilot, prospective and observational study that lasted 9months. All patients with HELLP syndrome treated at academic tertiary care women hospital accepted to participate. Sixteen patients were included. In ten patients (63%), schizocytes were detected following a blood smear test. Six patients (38%) were diagnosed with a partial expression deficiency of proteins regulating the complement system (CD 55 or CD 59). In nine patients (56%), an activation of the complement classical pathway was detected. In two patients (13%), an ADAMTS 13 activity below 30% was detected. Three patients (19%) were diagnosed with a folate deficiency and one (6%) with an antiphospholipid syndrome. All patients developed maternal or fetal morbidity including nine (56%) an acute kidney injury. All patients but one had at least one additional mechanism that could contribute to haemolysis, besides a simple physical injury. Larger studies should be promoted to understand haemolysis in HELLP syndrome.

Feeding difficulties in craniofacial microsomia: a systematic review.

Patients with craniofacial microsomia are at higher risk of developing obstructive sleep apnoea (OSA), as described in the previous article entitled "Obstructive sleep apnoea in craniofacial microsomia: a systematic review". These patients are also more likely to develop feeding difficulties. The present systematic review provides an overview of the literature on the prevalence, treatment, and follow-up of feeding difficulties in children with craniofacial microsomia (CFM). A search was performed in PubMed, Embase, Cochrane Library, and Web of Science for articles on CFM and feeding difficulties. The following data were extracted from the articles: number of patients, patient characteristics, presence of feeding difficulties, and the treatment and outcomes of feeding difficulties. Eight articles on CFM and feeding difficulties were included, two of which reported the prevalence of feeding difficulties (range 42-83%). Treatment mostly consisted of tube feeding. No information regarding follow-up was found in these articles. According to the literature, feeding difficulties are related to CFM. However, as there have been no prospective studies and few studies have presented objective measurements, no definitive conclusions can be drawn. Prospective studies are needed to determine the prevalence of feeding difficulties in patients with CFM.

Obstructive sleep apnoea in craniofacial microsomia: a systematic review.

Children with craniofacial microsomia (CFM) are at risk of obstructive sleep apnoea (OSA). This systematic review provides an overview of the literature on the prevalence of OSA in children with CFM. A search was performed in PubMed, Embase, Cochrane Library, and Web of Science for articles on CFM and OSA. The following data were extracted from the articles: number of patients, patient characteristics, presence of OSA, polysomnography outcomes, and the treatments and outcomes of OSA. We included 16 articles on CFM and OSA, four of which reported the prevalence of OSA (range 7-67%). Surgical treatment was more often described in these patients than conservative treatment. According to the literature, OSA is related to CFM. However, as there have been no prospective studies and few studies have presented objective measurements, no definitive conclusions can be drawn. Prospective studies are needed to determine the prevalence of OSA in patients with CFM.

Does the presence of von Willebrand factor in FVIII-deficient plasma influences the measurement of FVIII inhibitor titres in haemophilia A patients?

INTRODUCTION: Reliable measurement of FVIII inhibitor is critical in the follow-up of haemophilia A patients. We performed a multicentre study to evaluate whether the presence of von Willebrand factor (VWF) in FVIII-deficient plasma (FVIII-DP) influences FVIII inhibitor titres. METHODS: Six French haematology laboratories participated in this study. Three samples with varying FVIII inhibitor titres (1, 5 and 15 BU/mL) and one sample without any detectable FVIII inhibitor were tested using four different procedures for FVIII inhibitor assay. The Nijmegen method and a modified assay with imidazole were performed using FVIII-DP with and without VWF in the control mixture and as substrate plasma in the FVIII one stage assay (OSA). Each mixture (reference and test) was incubated for two hours at 37 °C with buffered normal pool plasma. RESULTS: Higher inhibitor titres were measured in 5 and 15 BU/mL samples when assays were performed with the Nijmegen method and FVIII-DP without VWF. When samples were diluted in imidazole buffer, similar inhibitor titres, close to expected values, were measured whether VWF was present in the FVIII-DP or not. The data obtained were also more accurate when residual FVIII activity levels between 40% and 60% were used to calculate inhibitor titres, despite a linear type I reaction kinetics. CONCLUSION: These results support the hypothesis that reliable FVIII inhibitor titres can be measured without the use of FVIII-DP containing VWF when an imidazole-modified assay is used.

Mandibular reconstruction in the growing patient with unilateral craniofacial microsomia: a systematic review.

The purpose of this systematic review is to provide an overview of the surgical correction of the mandible in unilateral craniofacial microsomia (UCM) performed in the growing patient, and its long-term outcome and stability. The following databases were searched: PubMed, Embase, Cochrane, and Web of Science. Articles reporting prospective and retrospective studies of patients not older than 16 years (N ≥ 4) who had undergone surgical correction of a craniofacial microsomia spectrum condition using grafts, osteotomies, distraction, or combinations of these, were reviewed. The period of follow-up was selected to be ≥1 year. After inclusion, the articles were evaluated on short- and long-term outcomes, relapse, and any increase in asymmetry following treatment. Thirty of 1611 articles were included in the qualitative synthesis. Analysis of the surgical mandibular correction of UCM showed that the outcome is not so much treatment-dependent, but patient-dependent, i.e. deformity gradation-dependent. The type I-IIa Pruzansky-Kaban patient had the best results with regard to minimal relapse and/or minimal increase in asymmetry. Single-stage correction of the asymmetry should be postponed until the permanent dentition stage. It can be concluded that in the treatment of the severely hypoplastic mandible, the patient will benefit from a multi-stage treatment protocol if indicated for functional or psychological problems.