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NeoReviews Apr 2021Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live...
Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live births. Primary or congenital craniosynostoses represent the majority of cases and consist of single-suture and multisuture synostoses. Multisuture synostoses are typically associated with distinct craniofacial syndromes, including Muenke syndrome, Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, and are thus categorized under syndromic craniosynostoses. Secondary causes of craniosynostoses include metabolic or hematologic disorders that affect bone metabolism and typically present much later than primary synostoses. The severity of the deformity and the presence of increased intracranial pressure dictate the need for early surgical intervention, prompting the importance of early recognition and timely referral. Infants with craniosynostosis are also at increased risk for neurodevelopmental impairment and thus require close follow-up and monitoring. The early recognition and referral of craniosynostosis is imperative for the optimization of management and minimization of potential neurologic impairments that may develop.
Topics: Craniofacial Dysostosis; Craniosynostoses; Humans; Infant, Newborn; Skull; Syndrome
PubMed: 33795400
DOI: 10.1542/neo.22-4-e250 -
Clinical Oral Investigations Mar 2022To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial...
OBJECTIVES
To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group.
MATERIAL AND METHODS
We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children.
RESULTS
Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: β = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: β = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: β = -1.70, p = 0.015; and PC1: p < 0.033).
CONCLUSIONS
In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls.
CLINICAL RELEVANCE
The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.
Topics: Acrocephalosyndactylia; Adolescent; Basic Helix-Loop-Helix Transcription Factors; Cephalometry; Child; Child, Preschool; Craniosynostoses; Humans; Syndrome
PubMed: 34904178
DOI: 10.1007/s00784-021-04275-y -
Cureus Dec 2023Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture,... (Review)
Review
Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture, which results in compensatory growth of cranial bones parallel to it. Syndromic craniosynostosis ensues when the cranial deformity is accompanied by respiratory, neurological, cardiac, musculoskeletal, and audio-visual abnormalities. The most common syndromes are Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes and craniofrontonasal syndrome. Each of these syndromes has distinct genetic mutations that contribute to their development. Mutations in genes such as FGFR, TWIST, and EFNB1 have been identified as playing a role in the development of these syndromes. Familiarity with the genetic basis of each syndrome is not only essential for identifying them but also advantageous for current pharmacological investigations. Surgical treatment is often necessary for syndromic craniosynostosis to correct the cranial deformities. Advances have been made in surgical techniques for each specific syndrome, but further research is needed to develop personalized approaches that address the unique symptoms and complications of individual patients, particularly those related to neurological and respiratory issues. This group of syndromes included in cranial synostosis presents significant educational and clinical interest due to the wide range of symptoms and the variable course of the disease, especially in the last decades when crucial advances in diagnosis and treatment have been achieved, altering the prognosis as well as the quality of life of these patients. In summary, this article provides a comprehensive overview of syndromic craniosynostosis, including the genetic mutations associated with each syndrome and the surgical treatment options available.
PubMed: 38222144
DOI: 10.7759/cureus.50448 -
Neuro-Chirurgie Nov 2019The aim of the present study was to review the literature on ENT disorders associated with craniosynostosis (CS), focusing on symptoms, diagnostic work-up, treatment and... (Review)
Review
OBJECTIVE
The aim of the present study was to review the literature on ENT disorders associated with craniosynostosis (CS), focusing on symptoms, diagnostic work-up, treatment and outcome.
METHODS
Publications were retrieved by consulting the PubMed® free search engine of the US National Library of Medicine. The term "craniosynostosis" was combined with the following key-words: ENT, apneas, OSAS, sleep-disordered breathing, tonsillectomy, deafness, hearing loss.
RESULTS
The main ENT disorders associated with CS are upper airway obstruction, chronic otitis and hearing loss. Obstructive sleep apnea-hypopnea syndrome (OSAS) is present in 7% to 67% of children suffering from CS and mainly results from midface stenosis with narrow nasal and rhinopharyngeal cavities. OSAS is diagnosed on polysomnography and airway obstruction levels are determined on wake or drug-induced sleep endoscopy and on CT or MRI. OSAS treatment can be surgical (mainly midface advancement, adenoidectomy and tonsillectomy, tracheostomy) or non-surgical (non-invasive ventilation, nasopharyngeal airway). Hearing impairment is frequently associated with CS. Its main cause is otitis media with effusion (OME) but ossicular malformations and sensorineural hearing loss (SNHL) are sometimes observed. SNHL is mostly found in Muenke syndrome. In view of the frequency and potential severity of these disorders into account, yearly ENT visits are recommended in children presenting with CS.
Topics: Airway Obstruction; Child; Craniosynostoses; Hearing Loss; Humans; Otorhinolaryngologic Diseases
PubMed: 31568777
DOI: 10.1016/j.neuchi.2019.09.015 -
European Journal of Orthodontics May 2022To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis,...
OBJECTIVES
To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis, compared with a Dutch control group without syndromes.
MATERIALS AND METHODS
This study included 60 patients (38 patients with Muenke syndrome, 17 patients with Saethre-Chotzen syndrome, and 5 with TCF12-related craniosynostosis), aged 5.8-16.8 years that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care, and Orthodontics, in Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands. Dental age was calculated according to Demirjian's index of dental maturity. The control group included 451 children without a syndrome.
RESULTS
Compared with the control group, dental development was delayed by an average of one year in 5- to 8-year-old patients with Muenke syndrome (P = 0.007) and in 8- to 10-year-old patients with Saethre-Chotzen syndrome (P = 0.044), but not in patients with TCF12-related craniosynostosis.
CONCLUSIONS
Our results indicated that dental development was delayed by one year, on average, in patients with Muenke syndrome and Saethre-Chotzen syndrome, compared with a Dutch control group without syndromes.
IMPLICATIONS
Our findings have improved the understanding of dental development in patients with Muenke and Saethre-Chotzen syndrome. These results can provide guidance on whether the orthodontist needs to consider growth disturbances related to dental development.
Topics: Acrocephalosyndactylia; Basic Helix-Loop-Helix Transcription Factors; Child; Child, Preschool; Craniosynostoses; Humans; Netherlands; Syndrome
PubMed: 34424951
DOI: 10.1093/ejo/cjab056 -
American Journal of Medical Genetics.... Aug 2019Muenke syndrome (MIM #602849), the most common syndromic craniosynostosis, results from the recurrent pathogenic p.P250R variant in FGFR3. Affected patients exhibit wide...
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.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Child, Preschool; Cohort Studies; Comorbidity; Craniosynostoses; Disease Management; Female; Gene Expression; Hearing Loss; Humans; Male; Middle Ear Ventilation; Mutation; Osteogenesis, Distraction; Otitis; Pedigree; Philadelphia; Receptor, Fibroblast Growth Factor, Type 3; Recurrence
PubMed: 31111620
DOI: 10.1002/ajmg.a.61199 -
Journal of Neurosurgery. Pediatrics Jul 2019The authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.
OBJECTIVE
The authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.
METHODS
This was a prospective observational cohort study of Muenke syndrome patients who underwent surgery for craniosynostosis within the first year of life. Symptoms and determinants of intracranial hypertension were evaluated by longitudinal monitoring of the presence of papilledema (fundoscopy), obstructive sleep apnea (OSA; with polysomnography), cerebellar tonsillar herniation (MRI studies), ventricular size (MRI and CT studies), and skull growth (occipital frontal head circumference [OFC]). Other evaluated factors included hearing, speech, and ophthalmological outcomes.
RESULTS
The study included 38 patients; 36 patients underwent fronto-supraorbital advancement. The median age at last follow-up was 13.2 years (range 1.3-24.4 years). Three patients had papilledema, which was related to ophthalmological disorders in 2 patients. Three patients had mild OSA. Three patients had a Chiari I malformation, and tonsillar descent < 5 mm was present in 6 patients. Tonsillar position was unrelated to papilledema, ventricular size, or restricted skull growth. Ten patients had ventriculomegaly, and the OFC growth curve deflected in 3 patients. Twenty-two patients had hearing loss. Refraction anomalies were diagnosed in 14/15 patients measured at ≥ 8 years of age.
CONCLUSIONS
Patients with Muenke syndrome treated with a single fronto-supraorbital advancement in their first year of life rarely develop signs of intracranial hypertension, in accordance with the very low prevalence of its causative factors (OSA, hydrocephalus, and restricted skull growth). This illustrates that there is no need for a routine second craniofacial procedure. Patient follow-up should focus on visual assessment and speech and hearing outcomes.
PubMed: 31323628
DOI: 10.3171/2019.5.PEDS1969 -
The Cleft Palate-craniofacial Journal :... Jun 2021To quantify soft tissue facial asymmetry (FA) in children with nonsyndromic and Muenke syndrome-associated unicoronal synostosis (NS-UCS and MS-UCS), hypothesizing that...
OBJECTIVE
To quantify soft tissue facial asymmetry (FA) in children with nonsyndromic and Muenke syndrome-associated unicoronal synostosis (NS-UCS and MS-UCS), hypothesizing that MS-UCS presents with significantly larger FA than NS-UCS.
DESIGN
Retrospective cohort study.
PATIENTS AND METHODS
Twenty-one children (mean age: 0.6 years; range: 0.1-1.4 years) were included in the study (NS-UCS = 14; MS-UCS = 7). From presurgical computed tomography scans, facial surfaces were constructed for analysis. A landmark guided atlas was deformed to match each patient's surface, obtaining spatially detailed left-right point correspondence. Facial asymmetry was calculated in each surface point across the face, as the length (mm) of an asymmetry vector, with its Cartesian components providing 3 directions. Mean FA was calculated for the full face, and the forehead, eye, nose, cheek, mouth, and chin regions.
RESULTS
For the full face, a significant difference of 2.4 mm ( = .001) was calculated between the 2 groups, predominately in the transverse direction (1.5 mm; < .001). The forehead and chin regions presented with the largest significant difference, 3.5 mm ( = .002) and 3.2 mm ( < .001), respectively; followed by the eye (2.4 mm; = .004), cheek (2.2 mm; = .004), nose (1.7 mm; = .001), and mouth (1.4 mm; = .009) regions. The transverse direction presented with the largest significant difference in the forehead, chin, mouth, and nose regions, the sagittal direction in the cheek region, and the vertical direction in the eye region.
CONCLUSIONS
Muenke syndrome-associated unicoronal synostosis presented with significantly larger FA in all regions compared to NS-UCS. The largest significant differences were found in the forehead and chin regions, predominantly in the transverse direction.
Topics: Child; Craniosynostoses; Facial Asymmetry; Humans; Imaging, Three-Dimensional; Infant; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 32969272
DOI: 10.1177/1055665620959983 -
Bone Reports Jun 2022Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial...
OBJECTIVE
Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating () 1-3 mutations. Gain-of-function mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with -related faciocraniosynostoses may present extra-cranial growth anomalies.
STUDY DESIGN
We retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for -related FCS between 2000 and 2021 at the Craniofacial Unit of Necker - Enfants Malades University Hospital in Paris, France.
RESULTS
We showed that -related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1-3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight.
CONCLUSIONS
Patients with -related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in -related faciocraniosynostoses and support the hypothesis that all conditions with activating mutations affect both membranous ossification and long bones.
PubMed: 35372644
DOI: 10.1016/j.bonr.2022.101524