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Molecular Syndromology Jun 2017Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the gene. Both...
Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with. We tabulated frequently asked questions from affected individuals and families, and a parent of an affected child and an affected adult woman offered personal testimonies. We focused on perception of illness, body satisfaction, and the consequences for an otherwise normal individual who has a disorder that interferes with body image. The importance of paying particular attention to the management of both the physical appearance and the consequences of these entities on the quality of life is stressed by the affected individuals themselves.
PubMed: 28690482
DOI: 10.1159/000472408 -
The British Journal of Ophthalmology May 1991The association of congenital ablepharon with the absence of eyelashes and eyebrows, a wide mouth (macrostomia), and auricular, nasal, genital, and other systemic...
The association of congenital ablepharon with the absence of eyelashes and eyebrows, a wide mouth (macrostomia), and auricular, nasal, genital, and other systemic anomalies has been termed the ablepharon macrostomia syndrome. One such case is reported which illustrates the importance of immediate postnatal ocular management to minimise severe visual loss.
Topics: Abnormalities, Multiple; Eyebrows; Eyelashes; Eyelids; Humans; Infant, Newborn; Macrostomia; Male; Surgical Flaps; Syndrome; Vision Disorders
PubMed: 2036354
DOI: 10.1136/bjo.75.5.317 -
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 -
BMC Pulmonary Medicine Aug 2019Ablepharon macrostomia syndrome (AMS) is a rare congenital malformation disorder caused by the autosomal-dominant mutations in gene TWIST2. Patients affected by the...
BACKGROUND
Ablepharon macrostomia syndrome (AMS) is a rare congenital malformation disorder caused by the autosomal-dominant mutations in gene TWIST2. Patients affected by the disease present abnormalities in ectoderm-derived structures mainly consisting in major facial dysmorphic features and rarely in visceral anomalies. The only laryngo-tracheal defect reported is malacia, with no reference to any anatomical stenosis. We describe a unique case of laryngo-tracheal stenosis in a woman, with genetically confirmed AMS currently followed at our Department.
CASE PRESENTATION
A 37-year-old Caucasian woman was admitted to the intensive care unit for acute dyspnea that required orotracheal intubation followed by tracheostomy. The bronchoscopy revealed abnormal tracheal tissue at the level of the cricoid and the first three tracheal rings reducing airway caliber by 80% (grade III according to the Cotton-Meyer classification). Treatment of the stenosis by means of temporary tracheostomy and corticosteroids therapy resulted in airway patency restoration and patient's return to her normal activities. Bronchoscopy at four and five months showed disappearance of the abnormal tissue and a residual anatomical laryngo-tracheal stenosis of about 20% (grade I according to the Cotton-Meyer classification) of the normal airway caliber.
CONCLUSIONS
To our knowledge, this is the first patient affected by AMS presenting with laryngo-tracheal stenosis.
Topics: Abnormalities, Multiple; Adrenal Cortex Hormones; Adult; Dyspnea; Eye Abnormalities; Female; Humans; Intubation, Intratracheal; Macrostomia; Mutation; Trachea; Tracheal Stenosis; Tracheostomy
PubMed: 31462237
DOI: 10.1186/s12890-019-0921-8 -
Clinical & Experimental Optometry May 2021
Topics: Abnormalities, Multiple; Eye Abnormalities; Humans; Macrostomia
PubMed: 33689605
DOI: 10.1080/08164622.2021.1878839 -
BMC Biology Dec 2020Zebrafish is a model organism widely used for the understanding of gene function, including the fundamental basis of human disease, enabled by the presence in its genome...
BACKGROUND
Zebrafish is a model organism widely used for the understanding of gene function, including the fundamental basis of human disease, enabled by the presence in its genome of a high number of orthologs to human genes. CRISPR/Cas9 and next-generation gene-editing techniques using cytidine deaminase fused with Cas9 nickase provide fast and efficient tools able to induce sequence-specific single base mutations in various organisms and have also been used to generate genetically modified zebrafish for modeling pathogenic mutations. However, the editing efficiency in zebrafish of currently available base editors is lower than other model organisms, frequently inducing indel formation, which limits the applicability of these tools and calls for the search of more accurate and efficient editors.
RESULTS
Here, we generated a new base editor (zAncBE4max) with a length of 5560 bp following a strategy based on the optimization of codon preference in zebrafish. Our new editor effectively created C-to-T base substitution while maintaining a high product purity at multiple target sites. Moreover, zAncBE4max successfully generated the Twist2 p.E78K mutation in zebrafish, recapitulating pathological features of human ablepharon macrostomia syndrome (AMS).
CONCLUSIONS
Overall, the zAncBE4max system provides a promising tool to perform efficient base editing in zebrafish and enhances its capacity to precisely model human diseases.
Topics: Abnormalities, Multiple; Animals; Base Sequence; Eye Abnormalities; Gene Editing; Humans; Macrostomia; Mutation; Zebrafish
PubMed: 33272268
DOI: 10.1186/s12915-020-00923-z -
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 -
The Indian Medical Gazette Mar 1904
PubMed: 29003962
DOI: No ID Found -
Clinical Case Reports Jul 2017Barber-Say syndrome is a rare disorder characterized by hypertrichosis, redundant skin, and facial dysmorphism. gene mutation previously described in this syndrome was...
Barber-Say syndrome is a rare disorder characterized by hypertrichosis, redundant skin, and facial dysmorphism. gene mutation previously described in this syndrome was identified in our patient. Genetic testing is recommended in patients presenting with these phenotypic abnormalities, along with their parents, to establish de novo or inherited mutations.
PubMed: 28680619
DOI: 10.1002/ccr3.1014 -
Case Reports in Ophthalmology 2015We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features...
We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features consistent with a severe phenotype of ablepharon-macrostomia syndrome (AMS) including a fish-like appearance of the mouth, rudimentary ears, absence of body hair, thin skin, absent nipples, abdominal distension, and genital abnormalities. Upon presentation, there was severe exposure keratopathy causing large bilateral sterile ulcers culminating in corneal melting of both eyes. An amniotic membrane graft was used to attempt to maintain the corneal surface integrity. However, because of the late presentation, the corneas could not be salvaged. Extensive surgical reconstruction of both eyelids and bilateral penetrating keratoplasty was ultimately performed successfully to protect the ocular surfaces while trying to maximize the visual potential. Early amniotic membrane grafting may be done at the bedside and may help preserve the ocular in patients with severe eyelid deformities until more definitive treatment is performed.
PubMed: 26600791
DOI: 10.1159/000441615