Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS–FREM complex disorders

Schanze, Denny; Harakaľová, Magdaléna; Stevens, Cathy A.; Brancati, Francesco; Dallapiccola, Bruno; Farndon, Peter; Ferraz, Victor Evangelista de Faria; McDonald‐McGinn, Donna M.; Zackai, Elaine H.; Wright, Michael J.; Lieshout, Stef van; Vogel, Maartje J.; Haelst, Mieke M. van; Zenker, Martin

doi:10.1002/ajmg.a.36119

Cited by 8 publications

(6 citation statements)

References 37 publications

(48 reference statements)

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“…Lastly, the patient reported by Larumbe et al [2011] clearly had severe congenital ichthyosis. One patient showing an overlap between Fraser syndrome and AMS was subsequently found to harbor a homozygous splice site mutation in FRAS1, confirming the diagnosis of Fraser syndrome [Cavalcanti et al, 2007;Schanze et al, 2013]. Fraser syndrome differs to BSS and AMS in the presence of cryptophthalmos, urinary tract defects, airway anomalies, and marked cutaneous syndactyly [Van Haelst et al, 2007].…”

Section: Differential Diagnosismentioning

confidence: 73%

Barber–Say syndrome and Ablepharon–Macrostomia syndrome: An overview

Maria

Mazzanti

Roche

et al. 2016

American J of Med Genetics Pt A

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Barber-Say syndrome (BSS) and Ablepharon-Macrostomia syndrome (AMS) are congenital malformation syndromes caused by heterozygous mutations in TWIST2. Here we provide a critical review of all patients published with these syndromes. We excluded several earlier reports due to misdiagnosis or insufficient data for reliable confirmation of the diagnosis. There remain 16 reliably diagnosed individuals with BSS and 16 with AMS. Major facial characteristics present in both entities, albeit often in differing frequencies, are excessive facial creases, hypertelorism, underdevelopment of the anterior part of the eyelids (anterior lamella), ectropion, broad nasal ridge and tip, thick and flaring alae nasi, protruding maxilla, wide mouth, thin upper vermillion, and attached ear lobes. In BSS a remarkable extension of the columella on the philtrum can be seen, and in both the medial parts of the cheeks bulge towards the corners of the mouth (cheek pads). Scalp hair is sparse in AMS only, but sparse eyebrows and eyelashes occur in both entities, and general hypertrichosis occurs in BSS. We compare these characteristics with those in Setleis syndrome which can also be caused by TWIST2 mutations. The resemblance between the three syndromes is considerable, and likely differences seem larger than they actually are due to insufficiently complete evaluation for all characteristics of the three entities in the past. It is likely that with time it can be concluded that BSS. AMS and Setleis syndrome form a continuum.

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Section: Differential Diagnosismentioning

confidence: 73%

Barber–Say syndrome and Ablepharon–Macrostomia syndrome: An overview

Maria

Mazzanti

Roche

et al. 2016

American J of Med Genetics Pt A

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“…She had congenital bilateral palpebral defects with micro‐symblepharon on the left and upper eyelid coloboma on the right, cutaneous syndactyly of both hands, right‐sided renal agenesis and left‐sided grade II hydronephrosis, a laryngeal web, and genital anomalies. The case has been reported along with molecular data in 2013 (Schanze et al, 2013).…”

Section: Clinical Descriptionsmentioning

confidence: 82%

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome

Kunz

Kayserili

Midro

et al. 2020

American J of Med Genetics Pt A

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Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals.

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“…As we shall see later, the phenotypic features of FS are extremely variable and pleiotropic, and several other distinct syndromes such as Manitoba oculotrichoanal syndrome and ablepharon-macrostomia syndrome may overlap FS and may suffer mutations in the FRAS/FREM complex. 38 , 53 – 56 …”

Section: Etiology and Pathogenesismentioning

confidence: 99%

“…A detailed discussion of the syndromic curiosities associated with upper eyelid coloboma, including Manitoba oculotrichoanal syndrome, ablepharon-macrostomia syndrome, amniotic band sequence, oculoectodermal syndrome, and neurocutaneous syndrome, is beyond the scope of the current discussion and is reviewed elsewhere. 34 , 53 – 56 , 96 – 127 The distinct facial and ocular features of some of these syndromes are outlined in Figure 6 .…”

Section: Rare Syndromic Associations With Congenital Upper Eyelid Colmentioning

confidence: 99%

Congenital Upper Eyelid Coloboma

Tawfik

Abdulhafez

Fouad

2015

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose:To review the recent literature and describe the authors’ experience with congenital upper eyelid coloboma.Methods:In this review, we will summarize the embryologic and etiopathogenetic bases of congenital upper eyelid coloboma, and study the published clinical reports. We will also attempt to briefly shed some light on the rarer syndromic curiosities associated with upper eyelid coloboma.Results:Congenital upper eyelid colobomas are one of the few nontraumatic oculoplastic emergencies that may occasionally present in the first few days of life with a corneal ulcer and may even present with impending perforation. They can present with or without corneopalpebral adhesions, may be isolated findings or a part of a larger spectrum of congenital anomalies as in the case of Fraser syndrome or Goldenhar syndrome, or could be associated with other rare curiosities that could challenge the clinician with a huge diagnostic dilemma.Conclusions:Existing literature dealing with congenital colobomas of the upper eyelid is fraught with nosologic problems, confusing etiologies, and overlapping clinical features. We attempted to clarify the salient clinical features, outline the management principles, and until a time in the not-so-distant future where advances in molecular genetic testing would help redefine the etiology and the diverse clinical spectrum of genetic diseases associated with upper eyelid colobomas, we propose a simplified classification scheme based on the relation of the coloboma to the cornea, the presence or absence of systemic features, and all the syndromic and nonsyndromic associations of congenital coloboma of the upper eyelid known today.

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Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS–FREM complex disorders

Cited by 8 publications

References 37 publications

Barber–Say syndrome and Ablepharon–Macrostomia syndrome: An overview

Barber–Say syndrome and Ablepharon–Macrostomia syndrome: An overview

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome

Congenital Upper Eyelid Coloboma

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