Ocular adnexal phenotype and management of a patient with mosaic expression of a mutation in TWIST2.

Ablepharon-macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are congenital ectodermal dysplasias associated with mutations in the TWIST2 gene. Among the ophthalmic anomalies that occur in these syndromes, underdevelopment of the anterior lamella of the eyelid is a defining feature. Reports of mosaic expression of TWIST2 mutations are extremely rare, with only five confirmed or suspected cases described to date. Mosaic expression of TWIST2 variants is correlated with a less severe phenotype than that reported for the typical expression of TWIST2 variants associated with BSS or AMS. Abnormal development of the anterior lamella appears to be a common feature in all cases of AMS with mosaic expression. Here, we describe the phenotype of a patient with mosaic expression of a TWIST2 mutation that is typically associated with AMS. We additionally describe the surgical approach employed in the treatment of this patient.

Blepharophimosis mental retardation syndrome Say-Barber/Biesecker/Young-Simpson type - new findings with neuroimaging.

We report on a female patient with blepharophimosis mental retardation syndrome of Say/Barber/Biesecker/Young-Simpson (SBBYS) type. Main findings in her were marked developmental delay, blepharophimosis, ptosis, cleft palate, external auditory canal stenosis, small and malformed teeth, hypothyroidism, hearing impairment, and joint limitations. We performed diffusion tensor magnetic resonance imaging (MRI) and tractography of the brain which showed inappropriate myelination and disturbed white matter integrity. Cytogenetic analysis, subtelomeric fluorescence in situ hybridization and comparative genomic hybridization failed to identify an abnormality. It remains uncertain whether the MRI findings are specific to the present patient or form part of the SBBYS syndrome.

A rare bilateral Tessier no. 6 and 7 clefts.

The authors describe a patient with bilateral Tessier no. 6 and no. 7 clefts. The case consists of macrostomia combined with maxillary, zygomatico-orbito-temporal deformities, dental anomalies and mandibular retrusion. In addition, the cleft is located bilaterally in the maxillary arch with a double deciduous posterior dentition. This is rare. The clinical and radiological features are reported and the treatment plans are discussed.

Macrostomía bilateral aislada congénita / Congenital isolated bilateral macrostomia

Introducción. Dentro de las malformaciones craneofaciales, la macrostomía bilateral aislada es una de las malformaciones más inhabituales, con una frecuencia del 0,3% de los niños con fisuras faciales. Consiste en una hendidura orofacial entre el maxilar superior y el inferior derivada de una alteración del primer arco branquial. Su etiología es desconocida, pero una de las teorías más establecidas es el error de fusión entre el maxilar superior y el inferior durante el desarrollo embrionario. Suele aparecer de manera aislada, sin estar asociada a otros defectos, en contraposición a la macrostomía unilateral, que normalmente forma parte de un síndrome específico. Observación clínica. Exponemos el caso de un recién nacido de sexo femenino que presenta a la exploración un alargamiento bilateral de la comisura bucal de un centímetro de longitud mostrando una apertura amplia, sin otra malformación externa asociada. Todas las exploraciones complementarias que se realizaron para detectar malformaciones asociadas fueron normales. La evolución el periodo neonatal fue correcta, salvo una succión débil en las primeras horas de vida que desapareció progresivamente. Comentarios. Es importante realizar una minuciosa exploración física y diferentes exploraciones complementarias, como ecografía transfontanelar y abdominal, serie ósea y ecocardiograma para encontrar otras anormalidades, en especial si es de presentación unilateral. El tratamiento es quirúrgico con una evolución favorable y donde el proceso de deglución y fonación está conservado(AU)

Introduction. Isolated bilateral macrostomia is one of the rarest malformations within the craniofacial defects, with a frequency of 0.3% of children with facial clefts. It is defined by the presence of an orofacial cleft between the upper and lower jawbone caused by an alteration of the first branchial arch. Its etiology is unknown but one of the most established theories is the error of fusion between upper and lower jaw during embryonic development. Usually it appears isolated, without being associated with other defects, in contrast to unilateral macrostomia, which most often presents in the context of a specific syndrome. Case report. We describe the case of a female newborn that presented a bilateral one-centimeter elongation of the mouth, showing a large opening without other associated external malformations. Imaging studies excluded internal malformations. The evolution was optimal in the neonatal period except for a weak suction in the first hours of life that gradually improved. Comments. In the presence of macrostomia, it is important to perform a thorough evaluation, including physical examination and imaging studies such as transfontanellar and abdominal ultrasound, echocardiography and skeletal series to evaluate for other abnormalities, especially in cases of unilateral presentation. Surgical treatment usually results in successful outcome with preservation of swallowing and phonation(AU)

Case report supporting that the Barber-Say and ablepharon macrostomia syndromes could represent one disorder.

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.

Bilateral macrostomia associated with aqueductal stenosis and glial heterotopias.

We report on an Italian boy, born to normal and nonconsanguineous parents with a prenatal diagnosis of ventriculomegaly and subependymal glial heterotopias. At birth bilateral macrostomia was diagnosed without other evident facial anomalies. Magnetic resonance imaging (MRI) showed triventricular hydrocephalus and aqueductal stenosis and confirmed the nodules of glial heterotopia. The bilateral macrostomia was surgically corrected with the vermilion square flap method and W-plasty technique and follow up MRI at 6 months showed mild increase of ventricular dilatation without signs of active hydrocephalus. The association between macrostomia and hydrocephalus has been reported only in rare cases of complex malformative syndromes but never with isolated macrostomia.

Fraser and Ablepharon macrostomia phenotypes: concurrence in one family and association with mutated FRAS1.

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.

An association between hemifacial microsomia and facial clefting.

PURPOSE: Hemifacial microsomia (HFM) is a relatively uncommon malformation, a far second to cleft lip/palate (CL/P). Transverse oral cleft ("macrostomia") is known to be associated with HFM, but there are also reports of concurrent CL/P. We undertook a retrospective study of patients with HFM to document the prevalence of facial clefting. The hypothesis is that the coexistence of facial clefts and HFM suggests a common pathogenic mechanism. MATERIALS AND METHODS: Records of 198 HFM patients from the database of the Craniofacial Centre at Boston Children's Hospital were reviewed. The age, gender, predominant side of HFM, OMENS classification, and presence, size, and type of cleft (CL/P, transverse oral cleft, or oro-ocular cleft) were documented. We performed chi 2 , t test, and Fishers exact analyses to evaluate the association of facial clefting with HFM. RESULTS: There were 100 males and 98 females in the HFM study group, with a mean age of 15.3 years (range, 1 to 50 years); 90 were right-sided (45%), 79 were left-sided (40%), and 29 were bilateral (15%). Twenty patients had a CL/P (10%), and of these 15 had unilateral CL/P (UCL/P), equally distributed between right and left sides, and 5 had bilateral CL/P (BCL/P). There were 9 males and 11 females with combined HFM and CL/P. Cleft of the oral commissure (macrostomia) was present in 46 (23.0%) of the HFM patients with a left-to-right-to-bilateral ratio of 5:6:1. There was a significant association between the predominant side of HFM and the side of CL/P ( P < .001) and macrostomia ( P

A new form of mandibulofacial dysostosis with macroblepharon and macrostomia.

We report on a girl aged 7 years with normal mental development but an unusual form of mandibulofacial dysostosis. The hallmarks of the syndrome are a round, flat face, severe hypertelorism, downslanting palpebral fissures extending to the temples, a broad nasal base, anteverted nares, small, posteriorly rotated ears, a long, smooth philtrum, a thin upper lip, striking macrostomia, retrognathism with reduced height of the mandible, and irregularly placed teeth, some to them missing.

Congenital shortening of the anterior lamella of all eyelids: the so-called ablepharon macrostomia syndrome.

The so-called ablepharon macrostomia syndrome is an extremely rate congenital condition that includes abnormal ears, an enlarged, fishlike mouth, absence of lanugo, redundant skin, and vertical shortening of all eyelids. Only four cases have been described so far. In these cases the nature of the eyelid anomalies has not been clearly defined. We report one more case showing that the condition is better described as a severe microblepharon because only the anterior lamella of the eyelids is shortened. The literature about this condition is reviewed, and oculoplastic treatment is discussed.

Ablepharon macrostomia syndrome.

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.

Focal dermal hypoplasia syndrome with incomplete transverse facial cleft and tumour of the lips.

A case of Goltz's syndrome complicated with both incomplete transverse facial cleft and characteristic tumour of the upper and lower lips is presented. Tumour excision and repair of defect were successfully performed.

Lid agenesis-macrostomia-psychomotor retardation-forehead hypertrichosis--a new syndrome?

We describe a boy with bilateral lid agenesis and total keratinization of cornea and conjunctiva, macrostomia, psychomotor retardation, forehead hypertrichosis, ocular hypertelorism, thin lips, abnormal auricles and nose, skin alterations, and other findings. Differential diagnosis with ablepharon-macrostomia syndrome is presented. Cause is unknown.

Ablepharon macrostomia syndrome.

The ablepharon macrostomia syndrome is a severe congenital condition that includes total absence of the upper and lower eyelids, failure of lip fusion that results in an enlarged, fish-like mouth, abnormally shaped ears and nose, absence of lanugo, ventral hernia, and ambiguous genitalia. In one such patient we were able to reconstruct the eyelids in a three-stage procedure. Redundant skin from the retroauricular area was used to create full-thickness grafts. The child later underwent successful mouth reconstruction. Although developmentally delayed, the child was eventually able to sit unassisted, to grasp objects, and to follow light with some fixation. Nystagmus was severe. The retina was attached in one eye and detached in the other. Corneal opacities present initially improved in one eye, allowing a view of the pupil and a normal anterior chamber.

Urological implications of the beckwith-wiedemann syndrome.

A significant number of children with the Beckwith-Wiedemann syndrome are prone to the development of nephroblastomas and adrenal carcinomas. Renomegaly, a prolonged tubular blush on excretory urography similar to that of medullary sponge kidney, and previously undescribed caliceal diverticula may be observed. Diligent followup is mandatory to detect early neoplasia. Suggestions are detailed based on reported case management.