Slant Of Palpebral Fissures Research Articles

Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debré type

To delineate a new syndrome of brain dysgenesis and cutis laxa based on the description of 11 patients belonging to nine unrelated families recruited through an international collaboration effort. Careful clinical assessment of patients from birth to the age of 23 years with follow-up studies ranging from 3 to 20 years. Biochemical studies of serum proteins glycosylation by isoelectric focusing and capillary zone electrophoresis were performed in 10 patients. Brain MRI studies using conventional methods were analyzed in eight patients. An expanded clinical spectrum of a syndrome comprising facial dysmorphia (enlarged anterior fontanelles, downward slant of palpebral fissures, prominent root of the nose), a connective tissue disorder (inguinal hernia, hip dislocation, high myopia), and neurologic impairment was defined. Early developmental delay was followed by onset of generalized seizures by the end of the first decade and a subsequent neurodegenerative course. A defect of N- or N- plus O-glycosylation of serum transferrins and ApoCIII was observed in 10 patients. An unusual cobblestone-like cortical malformation over the frontal and parietal regions was seen in eight patients and cerebellar abnormalities, including two patients with Dandy-Walker malformation, were observed in three patients. Our results suggest that autosomal recessive cutis laxa, Debré type, initially considered a dermatologic syndrome, is a multisystemic disorder with cobblestone-like brain dysgenesis manifesting as developmental delay and an epileptic neurodegenerative syndrome. It might represent a metabolic cause of Dandy-Walker malformation. It is associated with a deficient N- and-O glycosylation of proteins and shares many similarities with muscle-eye-brain syndromes.

Palpebral Fissure Changes After Monobloc Frontofacial Advancement in Faciocraniosynostosis

There is virtually no literature on the effect of correction of syndromal faciocraniosynostosis with monobloc advancement on the palpebral fissure shape. Using image processing software, we measured the effect of monobloc advancement on the position of the upper and lower eyelids as well as the palpebral fissure slant in a series of 18 patients with syndromal faciocraniosynostosis who had undergone surgery for correction of orbital and midface hypoplasia. For both eyes of each patient, 3 variables were measured on the pre- and postoperative photographs: the linear distances between the upper and lower eyelid margins, the pupil center and the angle between the inner and outer canthi. The globe protrusion was also measured on axial computed tomography scans before and after surgery. The results indicate that the exorbitism reduction induced by monobloc advancement is accompanied by a diminution of the distance between both eyelids and the pupil center. However, the downward slant of the palpebral fissure is increased after surgery. The data suggest that the lower and upper eyelid retraction seen preoperatively in the majority of patients with faciocraniosynostosis tend to be corrected when the frontofacial region is advanced by the monobloc. On the other hand, the surgery tends to lower the outer canthus, increasing the negative slant of the fissure. The postoperative changes induced by the frontofacial monobloc advancement need to be taken into account when the surgery is going to be performed.

Methimazole embryopathy: A contribution to defining the phenotype

It has been suggested that children prenatally exposed to methimazole may present some features in common but the phenotype remains to be defined. The reported facial features include upward slanted palpebral fissures, arched flared eyebrows and small nose with a broad bridge. Choanal atresia and other anomalies like esophageal atresia and aplasia cutis were also described with this embryopathy. Additionally, developmental delay was reported in some patients along with one of these major malformation. We present a patient with the mentioned facial features, developmental delay and radio-ulnar synostosis whose mother has been exposed to methimazole during pregnancy and any other ethiological cause could be recognize.

Molecular characterization of a novel translocation t(5;14)(q21;q32) in a patient with congenital abnormalities

Chromosomal translocations are frequently found to be associated with various malignant disorders as well as congenital abnormalities. We report the characterization of a novel reciprocal translocation t(5;14)(q21;q32) in a patient with congenital abnormalities manifested by severe mental retardation, athetotic tetraplegia, microcephaly, peculiar facies (upward slanting of palpebral fissures), clinodactyly of the fifth fingers, and overlapping toes. Using a JHGP24 lymphoblast cell line derived from this patient, metaphase fluorescence in situ hybridization with bacterial artificial chromosome and cosmid probes and subsequent molecular analysis mapped the translocation breakpoint to the nucleotide level. Sequence analysis of the breakpoint junctions revealed the presence of a homologous sequence, GTGGC, along with a single nucleotide substitution and an insertion in der(14), and a single nucleotide deletion in the der(5) chromosome. We also attempted to identify and characterize the transcripts near the breakpoint by 5' and 3' rapid amplification of cDNA ends. Although we found several transcripts near the breakpoint of chromosome 14, the lack of significant ORFs within these transcripts suggests they are likely to be non-coding RNAs. These transcripts may have an important role in the neurogenesis or differentiation.

The Ocular Manifestations of Jacobsen Syndrome: A Report of Four Cases and a Review of the Literature

Purpose: We report ophthalmic manifestations in four Jacobsen syndrome cases, review the literature, and suggest phenotype-genotype correlations. Methods: Chart review of Ocular Genetics Program patients at The Hospital for Sick Children, Toronto, Canada. Results: Four del11qter cases are presented. Hypertelorism/telecanthus, abnormally slanted palpebral fissures, abnormal retinal findings, nasolacrimal duct obstruction, anomalous extraocular muscles, amblyopia, and microcornea were found. Conclusions: We report typical findings and novel ocular presentations. Visual prognosis is generally good. Retinal dysplasia and coloboma seem associated with del11q23. ABCG4, NCAM, and Mfrp are candidate genes in this region that theoretically may be disrupted.

Plantar lipomatosis, unusual facies, and developmental delay: Confirmation of Pierpont syndrome

In 1998, Pierpont et al. reported on two unrelated boys with plantar lipomatosis, unusual facial phenotype, and developmental delay as a possible new MR/MCA syndrome. Here we report on a 2-year-old boy with similar manifestations: axial hypotonia in the first few months, prolonged feeding problems, moderate developmental delay, no speech development, deep palmar and plantar grooves, fat pads at the anteromedial aspect of the heels, and a distinct facial phenotype (high forehead, high anterior hairline, mild midfacial hypoplasia, remarkably narrow and upward slanted palpebral fissures, broad nasal ridge and tip, broad philtrum, bowed upper lip, "pouting" lower lip, full cheeks, and flat occiput). Brain MRI and MR spectroscopy studies showed relatively small frontal lobes, some widening of the lateral and third ventricles, and increased choline levels in the frontal white matter. Cytogenetic studies in lymphocytes and skin fibroblasts and whole genome micro-array CGH failed to show abnormalities. The present patient has a phenotype almost identical to that of the earlier reported children (Pierpont et al. [1998]: Am J Med Genet 75:18-21), which thereby validates this as a separate MR/MCA syndrome, appropriately designated Pierpont syndrome. The cause of the entity remains uncertain, the most likely etiologies being X-linked recessive or autosomal dominant genes.

Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957-1988

This presentation records the early history of the description of the broad thumb-hallux syndrome and attempts to update the current state of knowledge about this syndrome. Information was collected and reviewed on 571 individuals from the world literature, from communications with colleagues and families of affected individuals, and from personal observation. The diagnosis was established in most cases by confirming the concurrence of the constellation of major diagnostic criteria, including broad short terminal phalanges of the thumbs and halluces, with or without angulation deformity; characteristic facial appearance with beaked or straight nose, antimongoloid slant of palpebral fissures, apparent or clinical hypertelorism and grimacing smile; stature and head circumference (OFC) below 50th centile; mental, motor, social, and language retardation; stiff awkward gait; and incomplete or delayed descent of testes in males. Information on associated clinical factors, familial occurrence, and cytogenetic findings is presented.

Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure.

To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism. Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye. Visual acuity testing, cycloplegic refraction, slit-lamp biomicroscopy, and ophthalmoscopy were done on every patient. Corneal topography was obtained in 40 cooperative patients. External photographs of the midface were taken in 45 children. The degree of slanting of the palpebral fissures was evaluated based on the photographs. The statistical analysis tool used was repeated measures analysis of variance. Patients in whom photographic analysis was not available were excluded from the part of the statistical analysis dealing with eyelid slant. Palpebral fissure slant (P =.013) and gender (P =.0005) were highly correlated with the obliquity of cylinder axis. There was a possible correlation between gender and eyelid slant (P =.0594), with females having slightly larger degrees of upward palpebral fissure slanting and male more downward slanting of their fissures compared to published angles in an age-matched population. We found a statistically significant correlation between the degree of total astigmatism and a larger abnormal slant (P =.0192) and between the axis and magnitude of corneal astigmatism and abnormal slant (P =.0092). Higher degrees of eyelid slant (> 8 degrees or < -4 degrees ) increased the risk of high cylinder magnitude (> 3.00 D) by an odds ratio of 4.17 (95% CI: 1.03, 19.95). Children with astigmatism with large degrees of slanting of their palpebral fissures are at higher risk for high astigmatism (> 3.00 D). The axis of the astigmatism is highly correlated with the slanting of the palpebral fissure.

Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure

Purpose To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism. Methods Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye. Visual acuity testing, cycloplegic refraction, slit-lamp biomicroscopy, and ophthalmoscopy were done on every patient. Corneal topography was obtained in 40 cooperative patients. External photographs of the midface were taken in 45 children. The degree of slanting of the palpebral fissures was evaluated based on the photographs. The statistical analysis tool used was repeated measures analysis of variance. Patients in whom photographic analysis was not available were excluded from the part of the statistical analysis dealing with eyelid slant. Results Palpebral fissure slant ( P = .013) and gender ( P = .0005) were highly correlated with the obliquity of cylinder axis. There was a possible correlation between gender and eyelid slant ( P = .0594), with females having slightly larger degrees of upward palpebral fissure slanting and male more downward slanting of their fissures compared to published angles in an age-matched population. We found a statistically significant correlation between the degree of total astigmatism and a larger abnormal slant ( P = .0192) and between the axis and magnitude of corneal astigmatism and abnormal slant ( P = .0092). Higher degrees of eyelid slant (> 8° or < −4°) increased the risk of high cylinder magnitude (> 3.00 D) by an odds ratio of 4.17 (95% CI: 1.03, 19.95). Conclusions Children with astigmatism with large degrees of slanting of their palpebral fissures are at higher risk for high astigmatism (> 3.00 D). The axis of the astigmatism is highly correlated with the slanting of the palpebral fissure.

Racial and Ethnic Differences in Ocular Anatomy

Differences in eyelid structure are well described in the literature with respect to the Asian eyelid, but discussion of differences in eyelid structure between the other races is scarce. Most of the literature focuses on distinctions between “double” and “single” eyelids. Other clinical and surgical considerations are the presence of epicanthi and palpebral fissure slant. By understanding racial and ethnic anatomical differences, oculoplastic surgeons will be able to optimize function and aesthetics. Asians may have fuller, thicker-appearing upper eyelids with an absent or relatively lower upper lid (supratarsal) fold, making the distinction between the single and double eyelid (Figs 1, 2). The orbital septum of Asians fuses with the levator palpebrae aponeurosis at variable distances below the superior tarsal border, closer to the eyelid margin than in non-Asians. This hinders aponeurotic fibers from the levator palpebrae superioris from reaching the subcutaneous tissues, prohibiting the creating of a double eyelid crease. The fusion is above the superior tarsal

A subtelomeric cryptic unbalanced translocation der (1)t(1;18)(q44;q23) in a severely retarded girl: similarities and differences to the deletion 1q42/43-ter syndrome

We studied a girl with severe mental retardation, dysmorphic features (metopic ridging, mongoloid slant of palpebral fissures, short nose, thin vermilion, retrogenia, and deep-set ears) and multiple congenital abnormalities (microcephaly, agenesis of corpus callosum, flattened gyri, postaxial hexadactyly, and gastro-oesophageal reflux) for subtelomeric deletions using fluorescent in-situ-hybridization (FISH). Only one signal was found with the 1q probe and three signals with the 18q probe. Two of the 18q signals hybridized to the normal chromosome 18 and the third was found on 1q. Therefore, the patient has an unbalanced translocation t(1;18) resulting in monosomy 1q44 and trisomy 18q23-qter. The translocation was not detectable with classical cytogenetics. Comparison of the phenoytpe of patients with the 1q42qter and 1q43qter deletion syndrome, respectively, and our patient with a much smaller deletion revealed phenotypical and neurological similarities. This would suggest that the 1q- syndrome phenotype is due to deletions of genes present in the smaller deletion described here. Therefore, patients with a similar phenotype should be analyzed for submicroscopic deletions with the 1qtel probe.

Treatment of A-pattern Esotropia with Marked Mongoloid Slanting Palpebral Fissures

Background: The association of oblique palpebral fissures and A- or V-pattern has not been clarified. We report two cases of A-pattern esotropia with marked mongoloid slanting palpebral fissures associated with vertical displacement of the horizontal rectus muscle. Cases: Case 1 was a boy with Prader-Willi syndrome. He showed A-pattern esotropia with upward slanting palpebral fissures. Severe superior oblique muscle overaction was observed. Case 2 was a girl with meningocele. She also showed A-pattern esotropia with upward slanting palpebral fissures. Observations: In case 1, weakening surgery of the superior oblique muscles did not improve the A-pattern. Coronal images of computed tomography showed one-half-muscle-width upward displacement of both lateral rectus muscles. After downward transposition surgery of the lateral rectus muscles, the preoperative A-pattern of 25 prism diopters (PD) was successfully corrected to 10 PD. In case 2 also, upward displacement of both lateral rectus muscles was shown by computed tomography. The preoperative A-pattern of 26 PD was corrected to 4 PD postoperatively after upward transposition surgery of the medial rectus muscles. Conclusions: The vertical displacement of horizontal rectus muscles was considered the principal cause of A-pattern in these cases associated with marked mongoloid slanting palpebral fissures.

Rubinstein-Taybi syndrome: objective evaluation of craniofacial structure.

Rubinstein-Taybi syndrome (RTS) is a rare multiple congenital anomaly syndrome comprising mental and growth retardation, broad thumbs and great toes, and an unusual face. The classical facial appearance is well-established, striking and easy to recognize. It includes downslant of the palpebral fissures, epicanthic folds, ptosis, strabismus, highly arched palate, simple ears and a small mouth. The nose is distinctive with a beaked appearance, broad fleshy bridge, deviated septum and short low columella. Previous studies have documented considerable change in this facial phenotype with time. In this study, we evaluated 31 individuals with RTS from Great Britain and The Netherlands. They range in age from 1 to 39 years. Detailed craniofacial measurements were obtained on each subject and composite pattern profiles were compiled. There was remarkable concordance of patterns at all ages from infancy to adulthood. Microcephaly was present consistently. The head was relatively round with head width equal to head length. There was narrowness at the skull base with relative broadening of the minimal frontal diameter and lower facial width. The mouth was small and ears were broad and short. Eyes were wide-spaced in comparison to upper facial width and head circumference. The child under 4 years demonstrated some differences. Width and depth of the upper face exceeded that of the lower face, whereas with increasing age, mandibular dimensions were closer to normal than their maxillary counterparts. Despite these differences, the similarity of the profiles of all age groups seems to belie the phenotypic changes that can be appreciated subjectively. This suggests that major components of the change in appearance are those which have not been assessed in this study, such as palpebral fissure slant, deviation of the nasal bridge, presence of epicanthal folds or ptosis; or for which norms are not available, for example, beaking of the nose, and low nasal septum.

SONOGRAPHIC ASSESSMENT OF THE FETAL PALPEBRAL FISSURE SLANT—AN ADDITIONAL TOOL IN THE PRENATAL DIAGNOSIS OF SYNDROMES

Several syndromes and aneuploidies are associated with ocular abnormalities including up- and down-slanting palpebral fissures. We describe a technique for the sonographic assessment of the fetal palpebral fissure slant which was used in 70 normal pregnancies from 14 to 36 weeks of gestation. In a frontal view of the fetal face, the inferior angle between the palpebral fissure and the midline of the skull was determined. The median angle was 89°, with a range from 87° to 90°. In selected cases, sonographic assessment of the fetal palpebral fissure slant may be a helpful additional tool in the prenatal diagnosis of syndromes, as demonstrated in a fetus with Seckel syndrome associated with downslanting palpebral fissures and in a fetus with Down's syndrome associated with upslanting palpebral fissures. © 1997 by John Wiley & Sons, Ltd.

SONOGRAPHIC ASSESSMENT OF THE FETAL PALPEBRAL FISSURE SLANT—AN ADDITIONAL TOOL IN THE PRENATAL DIAGNOSIS OF SYNDROMES

Several syndromes and aneuploidies are associated with ocular abnormalities including up- and down-slanting palpebral fissures. We describes a technique for the sonographic assessment of the fetal palpebral fissure slant which was used in 70 normal pregnancies from 14 to 36 weeks of gestation. In a frontal view of the fetal face, the inferior angle between the palpebral fissure and the midline of the skull was determined. The median angle was 89 degrees, with a range from 87 degrees to 90 degrees. In selected cases, sonographic assessment of the fetal palpebral fissure slant may be a helpful additional tool in the prenatal diagnosis of syndromes, as demonstrated in a fetus with Seckel syndrome associated with downslanting palpebral fissures and in a fetus with Down's syndrome associated with upslanting palpebral fissures.

Nager acrofacial dysostosis: Management of a difficult airway

Nager acrofacial dysostosis, first described by Nager and deReynier in 1948, is a rare syndrome characterized by mandibulofacial dysostosis with associated radial defects. The facial features include downward slanting palpebral fissures, absent eyelashes in the medial third of the lower lids, mandibular and malar hypoplasia, dysplastic ears with conductive deafness, and variable degrees of palatal clefting. Upper limb malformation is a constant feature of Nager syndrome and ranges from thumb hypoplasia to absence of the radial ray. The maxillo-mandibular hypoplasia and associated retroplaced tongue set the stage for early and significant upper airway obstruction. The craniofacial anomalies and associated trismus make emergent airway intubation challenging. We present a case of Nager syndrome with life threatening airway obstruction unresponsive to conservative management. This case and a review of the literature emphasize the importance of early tracheotomy for these patients.

Váradi syndrome (OFD VI) or opitz trigonocephaly syndrome: Overlapping manifestations in two cousins

We report on 2 cousins, offspring of consanguineous matings, with multiple congenital anomalies. Square face, frontal bossing with metopic ridge, small anteverted nose, flat nasal bridge, slanted palpebral fissures, and epicanthal folds contributed to an unusual appearance. Multiple bucco-alveolar frenula and notched inferior alveolar ridges were present at birth and one had a notched uvula and submucous cleft of the hard palate. Both had congenital heart anomalies, micropenis, and cryptorchidism. Persistence of Müllerian structures was documented at necropsy in one patient. The surviving patient was mentally retarded and had unilateral central hexadactyly and partial agenesis of the corpus callosum. Bulimia and episodic hyperthermia were attributed to hypothalamic dysfunction. Results of unstimulated endocrine studies and gonadotropin releasing hormone (GnRH), and human chorionic gonadotropin (HCG) stimulation tests were normal. The manifestations of the 2 patients overlap those reported in the OFD VI and Opitz trigonocephaly syndromes.

Aarskog syndrome: report of a family with review and discussion of nosology.

Five individuals in one family, including dizygotic male twins, a half brother and their mother, had Aarskog syndrome (AS). Phenotypic variability is wide not only between mother and sons but also between sibs. Collectively, the affected relatives have the full spectrum of findings seen in AS. Based on analysis of this family and others from the literature, we derive primary and secondary diagnostic criteria for AS. Primary criteria include: short stature, hypertelorism, short nose with anteverted nares, maxillary hypoplasia, a crease below the lower lip, mild interdigital webbing with short and broad hands, short fifth finger with clinodactyly, and shawl scrotum. Secondary criteria include: abnormal auricles with fleshy lobules, posteriorly angulated ears, widow's peak, ptosis, downward slant of palpebral fissures, joint hyperextensibility, broad feet with bulbous toes, cryptorchidism, inguinal hernia, and prominent umbilicus. Literature pertaining to the clinical manifestations and genetics of AS is reviewed and nosology of similar syndromes is discussed.

De novo interstitial deletion of 1p (pter----p34.1::p32.3----qter).

We report a case of a 9 month old girl with a de novo interstitial deletion of 1p, karyotype 46,XX, del(1)(pter----p34.1::p32.3----qter). She had dysmorphic features including upward slanting palpebral fissures, a bulbous nose, a long philtrum, low set and malformed ears, a short neck, hypoplastic nails on both index fingers, widened interdigital spaces between the toes, dilated lateral ventricles, right hydronephrosis, a dilated right ureter, mental and motor developmental delay, and generalised hypotonia.

Trisomy 17p due to a t(8; 17) (p23; p11.2)pat translocation. Case report and review of the literature

We describe a female newborn girl with partial trisomy 17p, which was not detected at the initial cytogenetic investigation, but which later proved to be an unbalanced product of a paternal translocation t(8;17)(p23;p11.2). Comparison with the three previously reported patients suggests a clinically distinct "trisomy 17p syndrome", i.e. pre- and postnatal growth retardation, microcephaly, antimongoloid slanting of palpebral fissures, hypertelorism, long philtrum with thin upper lip, micrognathia and high-arched palate. Two of the four patients had a heart defect, and psychomotor developmental delay was evident in all four cases. In the present patient, the chromosomal anomaly was only detected after the finding of the autosomal reciprocal translocation in the father. The importance of cytogenetic investigations in parents of a MCA/MR child with apparently normal chromosomes is emphasized.