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American Journal of Human Genetics Jul 2015Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish...
Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.
Topics: Abnormalities, Multiple; Amino Acid Sequence; Animals; Base Sequence; Chromatin Immunoprecipitation; Exome; Eye Abnormalities; Eyelid Diseases; HeLa Cells; Hirsutism; Humans; Hypertelorism; Hypertrichosis; Macrostomia; Microscopy, Electron; Models, Molecular; Molecular Sequence Data; Mutation, Missense; Phenotype; Protein Conformation; Repressor Proteins; Sequence Analysis, DNA; Skin Abnormalities; Twist-Related Protein 1; Zebrafish
PubMed: 26119818
DOI: 10.1016/j.ajhg.2015.05.017 -
Sheng Li Ke Xue Jin Zhan [Progress in... Apr 2014
Topics: Abnormalities, Multiple; Eye Abnormalities; Humans; Macrostomia; Respiration; Sleep
PubMed: 25069316
DOI: No ID Found -
American Journal of Medical Genetics.... Dec 2013Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare congenital malformation syndrome. It overlaps clinically with Fraser syndrome (FS; OMIM 219000),...
Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare congenital malformation syndrome. It overlaps clinically with Fraser syndrome (FS; OMIM 219000), which is known to be caused by mutations in either FRAS1, FREM2, or GRIP1, encoding components of a protein complex that plays a role in epidermal-dermal interactions during morphogenetic processes. We explored the hypothesis that AMS might be either allelic to FS or caused by mutations in other genes encoding known FRAS1 interacting partners. No mutation in either of these genes was found in a cohort of 11 patients with AMS from 10 unrelated families. These findings demonstrate that AMS is genetically distinct from FS. It is proposed that it constitutes a separate entity within the group of FRAS-FREM complex disorders.
Topics: Abnormalities, Multiple; Carrier Proteins; Extracellular Matrix Proteins; Eye Abnormalities; Female; Fraser Syndrome; Humans; Macrostomia; Male; Mutation; Nerve Tissue Proteins; Phenotype
PubMed: 24115501
DOI: 10.1002/ajmg.a.36119 -
American Journal of Medical Genetics.... Dec 2011Ablepharon-Macrostomia syndrome (AMS) is a rare collection of findings characterized by absent or hypoplastic eyelids, fusion defects of the mouth with unfused lateral...
Ablepharon-Macrostomia syndrome (AMS) is a rare collection of findings characterized by absent or hypoplastic eyelids, fusion defects of the mouth with unfused lateral commissures, abnormal ears, ambiguous genitalia, skin differences including dry and coarse skin or redundant folds of skin, and developmental delay. Fewer than 20 patients have been reported to date. These include a parent and two children and a recent report of a father and daughter, therefore suggesting autosomal dominant inheritance. Here we present one additional sporadic case with an expanded phenotype. This patient has more significant hand and foot anomalies than previously reported.
Topics: Abnormalities, Multiple; Eye Abnormalities; Facies; Female; Humans; Infant, Newborn; Macrostomia; Phenotype
PubMed: 22002929
DOI: 10.1002/ajmg.a.34287 -
American Journal of Medical Genetics.... Apr 2011Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal...
Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal genitalia, and developmental delay in two-thirds of the reported patients. Additional anomalies include dry skin, growth retardation, hearing loss, camptodactyly, hypertelorism, absent zygomatic arches, and umbilical abnormalities. We present the second familial case of ablepharon-macrostomia syndrome in a newborn female and her 22-year-old father making autosomal dominant inheritance more likely than the previously proposed autosomal recessive transmission for this disorder. These cases likely represent the 16th and 17th reported cases of AMS and the first case suspected on prenatal ultrasound. Additionally, the child shows more prominent features of the disorder when compared to her father documenting variable expression and possible anticipation.
Topics: Abnormalities, Multiple; Chromosome Disorders; Eye Abnormalities; Female; Genes, Dominant; Humans; Infant, Newborn; Macrostomia; Male; Phenotype; Ultrasonography; Young Adult
PubMed: 21595001
DOI: 10.1002/ajmg.a.33900 -
Case Reports in Dermatological Medicine 2011Ablepharon syndrome is an extremely rare genetic problem that causes severe craniofacial deformities and numerous other abnormalities of the face, genitalia, and skin....
Ablepharon syndrome is an extremely rare genetic problem that causes severe craniofacial deformities and numerous other abnormalities of the face, genitalia, and skin. The literature regarding this condition is scarce. We present a case of this syndrome with dental manifestations, not reported before, and discuss its characteristics in order to increase the knowledge of this condition among the dental profession.
PubMed: 23198177
DOI: 10.1155/2011/593045 -
American Journal of Medical Genetics.... Oct 2009We report on a 7-year-old girl with unequivocal features of Barber-Say syndrome (BSS): generalized hypertrichosis especially at the back, dry lax skin, macrostomia, thin...
We report on a 7-year-old girl with unequivocal features of Barber-Say syndrome (BSS): generalized hypertrichosis especially at the back, dry lax skin, macrostomia, thin lips, cup-shaped ears, bulbous nose, hypoplastic nipples, and abnormal external genitalia. She also demonstrated conductive hearing impairment and microblepharon. BSS has been reported with ectropion (not present in our patient), but ablepharon and microblepharon (i.e., absent or hypoplastic eyelids) have always been considered as hallmarks of ablepharon macrostomia syndrome (AMS). This is the first report of microblepharon in BSS. Other authors have discussed that BSS and AMS could possibly represent one syndrome, and our report supports this hypothesis.
Topics: Abnormalities, Multiple; Child; Diagnosis, Differential; Eyelids; Female; Humans; Hypertrichosis; Macrostomia; Skin Diseases; Syndrome
PubMed: 19760652
DOI: 10.1002/ajmg.a.32993 -
Orvosi Hetilap Apr 2009The article presents abnormalities of the eyelids, the orbita and the periorbital areas. One part of these conditions disrupts vision, the main function of the eye. The... (Review)
Review
The article presents abnormalities of the eyelids, the orbita and the periorbital areas. One part of these conditions disrupts vision, the main function of the eye. The other reasons why they require correction are the aesthetic value of this distinctly visible area of the body and the necessity of improvement. The conditions and the management considerations for these disorders proposed by the author are the followings: ptosis palpebrae, anophthalmus, hyptophthalmus (ablepharon), and tumors.
Topics: Adolescent; Adult; Blepharoptosis; Child; Child, Preschool; Congenital Abnormalities; Eyelid Diseases; Eyelid Neoplasms; Eyelids; Female; Humans; Male; Treatment Outcome; Vision, Ocular; Young Adult
PubMed: 19362915
DOI: 10.1556/OH.2009.28594 -
American Journal of Medical Genetics.... Jul 2008Nonsyndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and toes that can be cutaneous or bony, unilateral or bilateral. We describe a...
Nonsyndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and toes that can be cutaneous or bony, unilateral or bilateral. We describe a patient with complex toe syndactyly and oligodactyly, some interesting skeletal hand findings and atypical facial features without other case like this described before. Cenani-Lenz syndrome (CLS) is a rare disorder with total syndactyly and irregular synostosis of carpal, metacarpal and phalanges, it may involve ulna and radius and digital rays may be absent, some of these were described with atypical facial features and one patient had renal hypoplasia and vertebral anomalies but our patient does not have the oligodactyly or syndactyly of the hands that is consistently present in all patients with CLS. The atypical facial features of our patient resemble Kabuki syndrome but oligodactyly and complex syndactyly have not been described in Kabuki syndrome and this patient has normal intelligence, and extreme eyelid defect (resembling ablepharon). Therefore, for our patient, we suggested to treat in a new condition of limb anomalies and atypical face.
Topics: Abnormalities, Multiple; Child; Craniofacial Abnormalities; Female; Fingers; Genes, Recessive; Hand; Humans; Phenotype; Radiography; Syndactyly; Syndrome; Toes
PubMed: 18512233
DOI: 10.1002/ajmg.a.32377 -
American Journal of Medical Genetics.... Feb 2007To date, Fraser syndrome (FS) and Ablepharon macrostomia syndrome (AMS) have been considered distinct disorders, but they share strikingly similar patterns of congenital...
To date, Fraser syndrome (FS) and Ablepharon macrostomia syndrome (AMS) have been considered distinct disorders, but they share strikingly similar patterns of congenital abnormalities, specifically craniofacial anomalies. While recent research has led to the identification of the genes FRAS1 and FREM2 as the cause of FS, the genetic basis of AMS continues to be enigmatic. We report on the concurrence of AMS-like and Fraser phenotypes in a Brazilian family. Both affected sibs were homozygous for a novel splice site mutation in the FRAS1 gene. Extensive studies on mRNA expression indicated that this mutation most likely leads to loss of function as most previously reported FRAS1 mutations associated with FS. We conclude that a phenotype resembling AMS is a rare clinical expression of FS with no obvious genotype-phenotype correlation. However, the molecular basis of "true" AMS which has been reported as a sporadic disorder in all cases but one, and so far with no relation to FS, is probably different and still needs to be further investigated.
Topics: Abnormalities, Multiple; Craniofacial Abnormalities; Extracellular Matrix Proteins; Female; Humans; Infant, Newborn; Macrostomia; Male; Mutation; Phenotype; Stillbirth
PubMed: 17163535
DOI: 10.1002/ajmg.a.31426