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American Journal of Medical Genetics Jul 1993We report on mandibulofacial dysostosis in 2 brothers born to normal nonconsanguineous parents, and a girl (F = 1/16) born to normal consanguineous parents. Normal...
We report on mandibulofacial dysostosis in 2 brothers born to normal nonconsanguineous parents, and a girl (F = 1/16) born to normal consanguineous parents. Normal clinical, skeletal, audiologic, and cephalometric studies in the parents, as well as the absence of limb anomalies in these children, exclude the autosomal recessive (Nager and Genée-Widemann) mandibulofacial dysostoses. The data of the present patients associated with the few additional reports on mandibulofacial dysostosis recurring in sibs, suggest the possibility of an autosomal recessive Treacher Collins-like mandibulofacial dysostosis.
Topics: Adult; Brazil; Child; Female; Genes, Recessive; Humans; Male; Mandibulofacial Dysostosis
PubMed: 8362908
DOI: 10.1002/ajmg.1320460611 -
American Journal of Medical Genetics Jun 1987Acute exposure to 400 mg/kg 13-cis retinoic acid (13-cis RA, isotretinoin, Accutane) on the ninth day postfertilization in mice (a time that corresponds to the fourth...
Acute exposure to 400 mg/kg 13-cis retinoic acid (13-cis RA, isotretinoin, Accutane) on the ninth day postfertilization in mice (a time that corresponds to the fourth week postfertilization in humans) results in malformations that characterize mandibulofacial dysostosis (MFD, Treacher Collins syndrome). Deficiencies in the infraorbital region and in the mandibular ramus and condyle, abnormalities of the secondary palate, and external ear malformations were observed. Light and scanning electron microscopic analyses of affected embryos illustrate that within 12 hours of maternal 13-cis RA treatment, markedly excessive (possibly premature) cell death occurs in regions where some of the cells are normally destined to undergo programmed cell death. Previous studies with retinoids have shown that they labilize lysosomal membranes and expand and strengthen regions of programmed cell death. Of particular interest for this study was cell death occurring in the dorsal (proximal) aspects of the maxillary and mandibular prominences of the first visceral arch, the second visceral arch, and the first visceral cleft, areas that correspond to the locations of the first and second arch ectodermal ("ganglionic") placodes and first closing membrane, respectively. The derivatives of this region are those that are severely affected in MFD. As described in previous reports from this laboratory, 13-cis RA is known to interfere with neural crest cells, resulting in major craniofacial malformations. However, the exposure times involved were earlier than those described herein. It is hypothesized that effects on the first and second arch ectodermal placodal cells at a time following the release from the neural folds of neural crest cells into the developing cranial region are of great significance in the pathogenesis of MFD. This is in contrast to the prevailing hypothesis that these malformations are the direct result of a primary interference with neural crest cells.
Topics: Animals; Cell Survival; Disease Models, Animal; Female; Isotretinoin; Mandibulofacial Dysostosis; Mice; Mice, Inbred C57BL; Tretinoin
PubMed: 3474899
DOI: 10.1002/ajmg.1320270214 -
American Journal of Medical Genetics.... May 2007Treacher Collins syndrome (TCS) is the prototypical mandibulofacial dysostosis syndrome, but other mandibulofacial dysostosis syndromes have been described. We report an...
Treacher Collins syndrome (TCS) is the prototypical mandibulofacial dysostosis syndrome, but other mandibulofacial dysostosis syndromes have been described. We report an infant with mandibulofacial dysostosis and an apparently balanced de novo 2;17 translocation. She presented with severe lower eyelid colobomas requiring skin grafting, malar and mandibular hypoplasia, bilateral microtia with external auditory canal atreasia, dysplastic ossicles, hearing loss, bilateral choanal stenosis, cleft palate without cleft lip, several oral frenula of the upper lip/gum, and micrognathia requiring tracheostomy. Her limbs were normal. Chromosome analysis at the 600-band level showed a 46,XX,t(2;17)(q24.3;q23) karyotype. Sequencing of the entire TCOF1 coding region did not show evidence of a sequence variation. High-resolution genomic microarray analysis did not identify a cryptic imbalance. FISH mapping refined the breakpoints to 2q31.1 and 17q24.3-25.1 and showed the 2q31.1 breakpoint likely affects the HOXD gene cluster. Several atypical findings and lack of an identifiable TCOF1 mutation suggest that this child has a provisionally unique mandibulofacial dysostosis syndrome. The apparently balanced de novo translocation provides candidate loci for atypical and TCOF1 mutation negative cases of TCS. Based on the agreement of our findings with one previous case of mandibulofacial dysostosis with a 2q31.1 transocation, we hypothesize that misexpression of genes in the HOXD gene cluster produced the described phenotype in this patient.
Topics: Chromosome Banding; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 2; Diseases in Twins; Female; Homeodomain Proteins; Humans; Infant, Newborn; Mandibulofacial Dysostosis; Translocation, Genetic
PubMed: 17431905
DOI: 10.1002/ajmg.a.31715 -
Cold Spring Harbor Molecular Case... Jun 2022Mandibulofacial dysostosis with microcephaly (MFDM) is a rare genetic disorder inherited in an autosomal dominant pattern. Major characteristics include developmental...
Mandibulofacial dysostosis with microcephaly (MFDM) is a rare genetic disorder inherited in an autosomal dominant pattern. Major characteristics include developmental delay, craniofacial malformations such as malar and mandibular hypoplasia, and ear anomalies. Here, we report a 4.5-yr-old female patient with symptoms fitting MFDM. Using whole-genome sequencing, we identified a de novo start-codon loss (c.3G > T) in the We examined expression in the patient by RNA sequencing and observed a notable functional consequence of the variant on gene expression in the patient. We identified a novel variant for the development of MFDM in humans. To the best of our knowledge, this is the first report of a start-codon loss in associated with MFDM.
Topics: Codon; Female; Humans; Mandibulofacial Dysostosis; Microcephaly; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 35732499
DOI: 10.1101/mcs.a006206 -
Oftalmologia (Bucharest, Romania : 1990) 1998Also known as Treacher-Collins or Franceschetti-Zwahlen-Klein syndrome, the mandibulofacial dysostosis is characterized by bilateral involvement of facial structures,...
Also known as Treacher-Collins or Franceschetti-Zwahlen-Klein syndrome, the mandibulofacial dysostosis is characterized by bilateral involvement of facial structures, including malar and mandibular hypoplasia, underdeveloped zygomatic bone, antimongoloid slant and external and middle ear anomalies. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. The authors report the case of a 19-years-old patient with characteristic cranio-facial malformations.
Topics: Abnormalities, Multiple; Adult; Humans; Male; Mandibulofacial Dysostosis; Refraction, Ocular; Visual Acuity
PubMed: 10418634
DOI: No ID Found -
American Journal of Medical Genetics.... Mar 2020Catel-Manzke syndrome is characterized by hand anomalies, Robin sequence, cardiac defects, joint hyperextensibility, and characteristic facial features. Approximately 40...
Catel-Manzke syndrome is characterized by hand anomalies, Robin sequence, cardiac defects, joint hyperextensibility, and characteristic facial features. Approximately 40 patients with Catel-Manzke have been reported, all with the pathognomonic bilateral or unilateral hyperphalangy caused by an accessory bone between the second metacarpal and proximal phalanx known as Manzke dysostosis. Here we present the first case of molecularly confirmed Catel-Manzke syndrome with Robin sequence but without Manzke dysostosis.
Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Female; Hand Deformities, Congenital; Humans; Hydro-Lyases; Mandibulofacial Dysostosis; Mutation; Pierre Robin Syndrome
PubMed: 31833187
DOI: 10.1002/ajmg.a.61436 -
The Cleft Palate-craniofacial Journal :... Mar 1999To monitor and compare facial morphology and growth in three individuals with variable expression of mandibulofacial dysostosis (MFD) in terms of changes in the skeletal...
OBJECTIVE
To monitor and compare facial morphology and growth in three individuals with variable expression of mandibulofacial dysostosis (MFD) in terms of changes in the skeletal profile and in terms of growth in the circummaxillary sutures and temporomandibular joints (TMJs).
DESIGN
Retrospective conventional profile roentgenography (mean age 9 to 18 years) and prospective roentgen stereometric analysis (RSA) (mean age 7 to 17 years).
SETTING
Center for Craniofacial Anomalies and Department of Plastic and Reconstructive Surgery, Malmö University Hospital, Sweden.
PATIENTS
The first three MFD patients seen by one of the authors (B.R.).
INTERVENTIONS
Surgery was performed at the Department of Plastic and Reconstructive Surgery. Implants were inserted at surgery under general anesthesia. Roentgen examinations were performed in connection with continued clinical evaluations and treatment.
MAIN OUTCOME MEASURES
All profile roentgenograms were traced and measured by one of the authors (K.-V.S.) using a conventional point-based analysis.
RESULTS
The more afflicted patient showed a greater total difference in profile morphology and growth from the norm and more pronounced effects of articular growth restriction. Little change in the skeletal profile was associated with considerable displacement of the jaws.
CONCLUSIONS
The variability in MFD expression and surgical procedures in our patients is reflected less in the skeletal profile morphology and growth and more in the displacement of the jaws.
Topics: Adolescent; Body Height; Cephalometry; Child; Child, Preschool; Female; Humans; Male; Mandibulofacial Dysostosis; Maxillofacial Development; Photogrammetry; Radiography, Dental; Reference Values
PubMed: 10213056
DOI: 10.1597/1545-1569_1999_036_0110_mdvifm_2.3.co_2 -
Indian Journal of Dental Research :... 1997Mandibulofacial dysostosis is readily recognized on the basis of a characteristic facial appearance caused by hard and soft tissue abnormalities of the face, including... (Review)
Review
Mandibulofacial dysostosis is readily recognized on the basis of a characteristic facial appearance caused by hard and soft tissue abnormalities of the face, including malformations of the ear. Generally, the abnormality is symmetrical. The psychological and social stigma associated with severe facial deformity makes this syndrome one of the most challenging reconstructive problems presented to the craniomaxillofacial surgeon.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Face; Female; Humans; Male; Mandibulofacial Dysostosis; Radiography
PubMed: 9495137
DOI: No ID Found -
The British Journal of Oral &... Sep 2014Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti-Zwahlen-Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard... (Review)
Review
Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti-Zwahlen-Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard and soft tissues of the first and second branchial arches. Early operations focus on maintaining the airway, protecting the eyes, and supporting auditory neurological development. Later operations include staged reconstruction of the mouth, face, and external ear. Bimaxillary surgery can improve the maxillomandibular facial projection, but correction of malar, orbital rim, and temporal defects may be more difficult. We present a clinical review of the syndrome with a chronological approach to the operations.
Topics: Age Factors; Face; Facial Bones; Humans; Mandibulofacial Dysostosis; Plastic Surgery Procedures
PubMed: 24776174
DOI: 10.1016/j.bjoms.2014.02.007 -
Clinical Genetics Jun 2013The human facial dysostoses can be subdivided into mandibulofacial dysostoses (MFDs) and acrofacial dysostoses (AFDs). The craniofacial phenotypes of the two groups of... (Review)
Review
The human facial dysostoses can be subdivided into mandibulofacial dysostoses (MFDs) and acrofacial dysostoses (AFDs). The craniofacial phenotypes of the two groups of patients are similar. Both types are thought to be related to abnormal migration of neural crest cells to the pharyngeal arches and the face. The craniofacial anomalies shared by the two groups consist of downslanting palpebral fissures, coloboma of the lower eyelid, from which the eyelashes medial to the defect may be absent, hypoplasia of the zygomatic complex, micrognathia, and microtia, which is often associated with hearing loss. These facial deformities are associated with limb anomalies in the AFDs. All MFDs present with the typical craniofacial phenotype, but some have additional features that help to distinguish them clinically: intellectual disability, microcephaly, chest deformity, ptosis, cleft lip/palate, macroblepharon, or blepharophimosis. The limb anomalies in the AFDs can be classified into pre-axial, post-axial, and others not fitting into the first two AFD types. Of the pre-axial types, Nager syndrome and of the post-axial types, Miller syndrome are the best-known disorders of their AFD subgroups. Several other AFDs with unknown molecular genetic bases, including lethal ones, have been described. This article reviews the MFDs and AFDs published to date.
Topics: Abnormalities, Multiple; Craniofacial Abnormalities; Genetic Predisposition to Disease; Humans; Mandibulofacial Dysostosis; Phenotype; Syndrome
PubMed: 23565775
DOI: 10.1111/cge.12123