Small Nose Research Articles

Axenfeld–Rieger anomaly and Axenfeld–Rieger syndrome: Clinical, molecular‐cytogenetic, and DNA array analyses of three patients with chromosomal defects at 6p25

Clinical phenotypes of and genetic aberrations in three unrelated Japanese patients with Axenfeld-Rieger anomalies and various accompanying malformations of systemic organs are described. GTG-banded chromosome analysis showed terminal deletions of the short arm of chromosome 6 in two patients and an inversion, inv(6)(p25q14), in the other. FISH and DNA array analyses revealed that the two patients with deletions had 5.0-5.7 Mb and 6.6 Mb 6p terminal deletions, respectively, and FOXC1 was apparently deleted in both patients. In the other patient, the inversion breakpoint at 6p25 was estimated to be in or very close to the FOXC1 locus, but DNA array analysis did not reveal a deletion around the breakpoint. Common extraocular findings in these patients included broad forehead, brachycephaly, hypertelorism, downslanting palpebral fissures, small anteverted nose, and cardiac defects. Two patients also exhibited autistic characteristics. The two patients with deletions exhibited poor muscle tone and developmental delays. Most of these extraocular findings were similar to those found in previous patients with FOXC1 mutations and distinct from those found in patients with PITX2 mutations, who frequently develop umbilical and dental anomalies. We suggest that the psychomotor retardation is a clinical manifestation associated with a deletion of multiple contiguous genes in the 6p terminus and that this phenomenon is similar to the 6p25 deletion syndrome. Understanding the relationship between genetic lesions and the spectrum of extraocular findings in patients with Axenfeld-Rieger anomalies may lead to better clinical management.

Phenotypic spectrum associated with CASK loss-of-function mutations

BackgroundHeterozygous mutations in the CASK gene in Xp11.4 have been shown to be associated with a distinct brain malformation phenotype in females, including disproportionate pontine and cerebellar hypoplasia.MethodsThe study characterised...

Injerto columelar extendido angulado. Método para prevenir la rotación cefálica y lateral de los injertos de cartílago en la punta nasal

The mestizo patient usually has a small nose, with wide base, round nostrils and convex dorsum. The alar cartilages are weak, thin and short, providing a def...

P02-208 - Xq28 duplication in a boy with mental retardation, hyperkinesia and dysmorphic features - a case report

IntroductionX-linked mental retardation (XLMR) is a common, clinically complex and genetically heterogeneous disease arising from many mutations along the X chromosome. Although research during the past decade has identified >90 XLMR genes, many more remain uncharacterized. In XY males, duplication of any part of the X chromosome leads to functional disomy of the corresponding genes.ObjectiveIn this paper we present the case of a boy with a syndrome of Xq28 duplication. Methods: We present a 6 years old boy, admitted in the Department of Pediatric Psychiatry for evaluation. He presented sever mental retardation, autistic features, speech delay, hyperkinesia, and dysmorphic features (high forehead, partial palpebral ptosis, small nose, carp-shaped open mouth, micrognathia), recurrent infections. Cerebral MRI was normal. Genetic investigations, including katyotype with GTG banding and array-CGH, were performed.ResultsArray-CGH indicated a dup(X)(q28) of less than 1.5 Mb. There were 15 duplicated genes, including MECP2 gene, which is involved in autism and mental retardation.ConclusionsDuplications at Xq28 are often associated with autistic features/non-syndromic MR; alterations in MECP2 gene (duplicated in our patient) are described in Rett syndrome or as a specific phenotype. The alteration occurring at Xq28 band is responsible for the patient’s phenotype. Clinical manifestation of this child will be compared with those of other patients with the same duplication previously described to further delineate this syndrome.

A girl with metopic synostosis and trisomy 13 mosaicism: Case report and review of the literature

Trisomy 13, or Patau syndrome is a rare chromosomal disorder characterized by a triad of cleft lip and palate, postaxial polydactyly and microcephaly. Complete, partial, or mosaic forms of the disorder can occur. Mosaic trisomy 13 is very rare, it occurs in only 5% of all patients with trisomy 13 phenotype. Metopic synostosis (MS) is premature fusion of the metopic suture, which is part of the frontal suture. It results in a V-shaped abnormality at the front of the skull. MS may occur in a syndromic or nonsyndromic form. We report on a 24-day-old girl with hypotonia, MS, trigonocephaly, capillary hemangioma, hypotelorism, upward slanting palpebral fissures, epicanthal folds, small nose with anteverted nares, high palate, ankyloglossia, long philtrum, low-set ears, short neck, postaxial polydactyly of both hands and feet and congenital heart defect. Cytogenetic analysis demonstrated trisomy 13 mosaicism; 46,XX[58]/47,XX,+13[42]. Although MS has been previously reported in complete and partial forms of trisomy 13, it has not been reported in mosaic form of trisomy 13. Our report supports the evidence that trisomy 13 causes MS. It also emphasizes the need for cytogenetic investigations in patients presenting with MS and multiple congenital anomalies for providing accurate diagnosis, genetic counseling, and prenatal diagnosis.

Craniomicromelic syndrome: First report in a male

We report on craniomicromelic syndrome in a male fetus. This case had the previously reported features of prenatal onset growth retardation, underossified cranial bones, wide sutures and fontanels, small face as compared to head, small palpebral fissures, pinched nose, microstomia, micrognathia, and narrow thorax. The consistent combination of these features with short appearing limbs as observed in this case establishes this syndrome as a distinct entity.

Phenotypic and dermatological manifestations in Down Syndrome

Down syndrome (DS) is associated with various uncommon dermatological disorders and increased frequency of some common dermatoses. This study was conducted over a 2-year period to evaluate the frequency of phenotypic and dermatologic manifestations in patients with Down syndrome in south India. The most common phenotypic manifestations that characterize DS include the epicanthic fold (93.7%), brachicephaly (90.6%), flat nasal bridge (84.2%), upward angle of eyes (83.2%), wide gap between first and second toe (81.1%), clinodactyly (77.9%), small nose (74.7%), short broad neck (72.6%), single palmar crease (61.1%), increased nuchal skin fold (61.1%), and fissured tongue (52.6%). The most common dermatological manifestation seen in patients with DS were lichenification, xerosis, dental anomaly, fine, sparse hair, and delayed dentition. Alopecia areata was seen in 9.4 percent of patients and tended to be severe. Infections were relatively less common in our study. Our study has highlighted many phenotypic features and dermatoses, which may help provide better care for patients and counseling to the families.

Effects of the histamine H1 antagonist chlorcyclizine on rat fetal palate development

The effects of histamine H1 antagonist chlorcyclizine on rat palate development were characterized following in utero exposure. To identify the optimum dose for inducing cleft palate, pregnant rats were administered 30, 60, or 90 mg/kg chlorcyclizine on Gestation Days 11 to 14. Fetal palate gene expression was also assessed after 90 mg/kg chlorcyclizine at 8, 15 and 30 hours post-dose on Gestation Day 14 using microarray and qRT-PCR. Rats in the 60- and 90-mg/kg groups exhibited adverse clinical signs and body weight loss. Rats in the 90-mg/kg group also demonstrated increases in late resorptions and decreases in fetal weight. Effects in the low-dose group were limited to decreases in body weight gain. Fetal assessment on Gestation Day 21 revealed that findings were limited to the 60- and 90-mg/kg groups, and included cleft palate (80% of litters for both groups), high arched palate, small nose, micrognathia, high domed head, digits shortened/absent and small limb. The fetal incidence of cleft palate was higher at 90 mg/kg, thus this dose was selected to assess palate gene expression. The altered genes associated with chlorcyclizine-induced cleft palate included Wnt5a, Bmp2, Bmp4, Fgf10, Fgfr2, Msx1, and Insig1 but the magnitude of the change was relatively small (1.5- to 2-fold). Expression of several genes involved in palate, limb and digit development was altered in the fetal palate following in utero exposure to chlorcyclizine. The subtle perturbation and interplay of these genes may have profound effects on the dynamics of fetal palate development.

P.R672C Mutation of MYH3 Gene in an Egyptian Infant Presented with Freeman-Sheldon Syndrome

To define the mutation type in a clinically suspected Egyptian child with Freeman-Sheldon syndrome (FSS); it involves certain skeletal malformations with some facial characteristics; skeletal malformations include camptodactyly with ulnar deviation, talipes equinovarus, while the facial characteristics include deep-sunken eyes with hypertelorism, long philtrum, small pinched nose and pursed mouth. Amplification of exon 17 of the embryonic myosin heavy chain (MYH3) gene was done using one forward and two different reverse primers, and then the cleaned PCR product was sequenced. A de novo missense mutation (c.2014C>T with replacement C > Y) in MYH3 gene leading to change of arginine at position 672 by cytosine in protein sequence. Mutation analysis remains to be the standard way for definitive diagnosis in FSS. The authors currently report, for the first time in an Egyptian infant aged 16 months who presented with FSS, a c.2014C>T missense mutation of MYH3 gene, with no family history or consanguinity.

Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24

Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by hypoplasia of the mandible and clavicles, acro-osteolysis, and lipodystrophy due to mutations in LMNA or ZMPSTE24. Only six MAD patients are reported so far with ZMPSTE24 mutations and limited phenotypic data are available for them. Here, we report on two brothers (4 years and 9-month old) with early onset MAD due to ZMPSTE24 mutations in whom thin skin was noted as early as 5 months of age. Both had micrognathia, mottled hyperpigmentation, and enlarged fontanelles but little evidence of lipodystrophy. There was no delay of mental development. The older brother had small pinched nose, short clavicles, acro-osteolysis, stunted growth, joint stiffness, and repeated fractures. There was no evidence of renal disease. Both patients were compound heterozygotes harboring a previously reported missense ZMPSTE24 mutation, p.Pro248Leu, and a novel null mutation, p.Trp450stop. These patients and the review of literature reveal that compared to MAD patients with LMNA mutations, those with ZMPSTE24 mutations develop manifestations earlier in life. Other distinguishing features in MAD due to ZMPSTE24 mutations may include premature birth, renal disease, calcified skin nodules, and lack of acanthosis nigricans. We conclude that in patients with MAD due to ZMPSTE24 mutations, the onset of disease manifestations such as thin skin and micrognathia occurs as early as 5 months of age. In these patients, skeletal phenotype presents earlier whereas lipodystrophy and renal disease may occur later in life.

Effects of Insert Nose Radius and Processing Cutting Parameter on the Surface Roughness of Aisi 316 Stainless Steel

The effects of different cutting parameters, insert nose radius, cutting speed and feed rates on the surface quality of the stainless steel to be use in medical application. Stainless steel AISI 316 had been machined with three different nose radiuses (0.4 mm 0.8 mm, and 1.2mm), three different cutting speeds (100, 130, 170 m/min) and feed rates (0.1, 0.125, 0.16 mm/rev) while depth of cut keep constant at (0.4 mm). It is seen that the insert nose radius, feed rates, and cutting speed have different effect on the surface roughness. The minimum average surface roughness (0.225µm) has been measured using the nose radius insert (1.2 mm) at lowest feed rate (0.1 mm/rev). The highest surface roughness (1.838µm) has been measured with nose radius insert (0.4 mm) at highest feed rate (0.16 mm/rev). The analysis of ANOVA showed the cutting speed is not dominant in processing for the fine surface finish compared with feed rate and nose radius. Conclusion, surface roughness is decreasing with decreasing of the feed rate. High nose radius produce better surface finish than small nose radius because of the maximum uncut chip thickness decreases with increase of nose radius.

First Night on Call in Emergency Psychiatry

First Night on Call in Emergency Psychiatry

Anthropometric and aesthetic analysis of the Indian American woman's face

This is the first study defining the facial anthropometric and aesthetic measurements in Indian American women (IAW). This is a prospective cohort study involving evaluation of facial photographs. Frontal, lateral and basal photographs were taken of IAW (n=102), and 30 anthropometric measurements were determined. Proportions were compared with published North American white women (NAWW) norms. Judges (n=6) evaluated the photographs for aesthetics using a visual analogue scale. Attractive IAW (top 15%) were compared with average IAW (remaining 85%) and average NAWW. All completed a facial self-esteem survey. There were significant differences between IAW and NAWW in 25 of 30 facial measurements. Six measurements correlated with aesthetic scores: intercanthal distance, mouth width, nasolabial angle, midface height 2, ear length and nasal height. Attractive IAW had nine measurements approximating NAWW features, 15 measurements similar to average IAW values and two measurements distinct from both average IAW and average NAWW. Attractive IAW had higher facial self-esteem scores than average IAW. Facial measurements in IAW are much different from NAWW, and these results will assist in preoperative planning. Several features are correlated with attractiveness in IAW: larger and wider-set eyes, a smaller midface, a smaller nose with greater tip rotation, smaller ears and a larger mouth. Attractive IAW display many measurements typical of average IAW and several measurements that reflect average NAWW values. These results contribute to concepts of transcultural aesthetics--for a minority ethnic group, facial beauty appears to be an assimilation of deep-rooted ethnic features with prevailing cultural traits and aesthetic standards.

Soft tissue facial morphometry in subjects with Moebius syndrome

Moebius syndrome is a congenital facial palsy associated with the impairment of ocular abduction. The three-dimensional characteristics of the facial soft tissues of 12 male and 14 female subjects [3-52 yr of age (mean age + standard deviation: 17 + 14 yr)] were measured using a non-invasive, computerized system; facial volumes, areas, angles, and distances were computed and compared with those obtained in reference subjects of the same age and gender. When compared with reference subjects, patients with Moebius syndrome had a more prominent and hyperdivergent face in the sagittal plane, a smaller and more prominent upper facial third; a smaller middle facial width; a smaller nose; smaller mandibular volume, depth, corpus length, and ramus height; and a more posterior positioned mandible, with a less prominent chin. In conclusion, patients with Moebius syndrome had a tendency towards a skeletal Class II pattern. These morphological variations may be the combined effect of a general alteration of the motor and sensitive facial nerves, including the trigeminal nerve, and of a maldevelopment of the brainstem.

A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation

To report a case of oculodentodigital dysplasia syndrome (ODDD) with a heterozygous mutation in GJA1 (connexin 43) gene. A 9-year-old girl visited our hospital complaining of visual disturbances. The patient had microphthalmia, a small nose with hypoplastic alae nasi, and syndactyly. Visual acuity with prescribed glasses improved to 0.5 (1.2) OU 2 months after the first visit. She was satisfied with the new glasses and the improvement in visual acuity. Genomic DNA was extracted from leukocytes of the patient's peripheral blood in accordance with standard procedures, after obtaining parental informed consent. We amplified GJA1 exon 2 from her genomic DNA by the PCR method, and sequenced the product using the dye terminator method. S5C (c. 13A > T), a novel mutation in exon 2 of GJA1, was found in the patient. The parents had no mutation of GJAI, nor was there any sign of abnormality in other family members. No similar mutation could be found in the 50 genotyped normal subjects in the control group. A novel GJA1 mutation was detected in a Japanese ODDD patient. Glaucoma complications associated with ODDD have already been reported. Careful long-term monitoring and treatment are also necessary.

Distal Trisomy of 10q with Distal Monosomy of 15q Due to a Paternal Translocation

Distal trisomy of 10q is a rare chromosomal abnormality. Distal deletions of the terminal long arm of chromosome 15 have rarely been described. We report on a male infant with low birth weight and microcephaly, a flat face with a spacious forehead, low-set ears, blepharophimosis, microphthalmia, a small nose, and a depressed nasal bridge. Microarray comparative genomic hybridization identified that he had the karyotype 46, XY, der (15) t (10;15) (q25.2;q26.2) pat, with chromosomal breakpoints at 10q25.2 and 15q26.2. This male neonatal case had an unbalanced translocation inherited from his father who was a balanced carrier with the karyotype 46, XY, t (10;15) (q25;q26). The neonate had a partial trisomy of the long arm of chromosome 10 with a partial monosomy of distal 15q. The clinical features were in agreement with previous descriptions and allowed us to propose a growth retardation phenotype for this neonate case.

Thin triangular blunt-nosed plate in a viscous hypersonic flow

The effect of a small blunt nose on the hypersonic flow past a thin, high-sweep and high-aspect-ratio plate at small incidence is investigated. The analysis is made by means of numerical simulation within the framework of the parabolized Navier-Stokes equations and the Euler equations in combination with approximate methods for calculating the heat transfer. The results are compared with the data of experiments in which some nontrivial features of the heat flux distributions over the thin plate surface were revealed.

A Procedure to Prevent Cephalic Rotation of Cartilage Grafts in the Nasal Tip

The mestizo patient usually has a small nose with a wide base, round nostrils, and a convex dorsum. The alar cartilages are weak, thin, and short, providing deficient structural support and poor definition of the nasal tip. Cartilage grafts in the nasal tip are very often used to correct this condition, but a common problem of this procedure is the cephalic or lateral rotation of these grafts. We used an angulated extended columellar graft to give columellar support and projection to nasal tip grafts for better control and prediction of the position and effect of these grafts. The surgical protocol included a medical history, development of a surgical plan by analysis of the deformity, and the use of pre- and postoperative photographs taken at both intermediate and long-term follow-up visits for evaluation of the results. Sixty-seven patients underwent surgery using this procedure, 56 with an open technique and 11 with a closed technique. Follow-up ranged from 6 months to 4 years. The results obtained were satisfactory, showing better control and prediction of the shape of the nasal tip. The angulated extended columellar graft provides better control of the projection and angularity of cartilage grafts placed in the nasal tip.

Toriello–Carey syndrome in a patient with a de novo balanced translocation [46,XY,t(2;14)(q33;q22)] interrupting SATB2

Toriello-Carey syndrome (TCS; OMIM 217980) is a multiple congenital anomaly syndrome characterized by the common manifestations of corpus callosum agenesis, cardiac defects, cleft palate/Robin sequence, hypotonia, mental retardation, postnatal growth retardation and distinctive facial dysmorphology (including micrognathia, telecanthus, small nose and full cheeks). Both autosomal recessive and X-linked inheritance have been proposed, but chromosomal abnormalities involving disparate loci have also been detected in a small number of cases. We report a patient with classical features of TCS and an apparently balanced de novo translocation between chromosomes 2 and 14 [46,XY,t(2;14)(q33;q22)]. Molecular characterization revealed direct interruption of the special AT-rich sequence-binding protein-2 (SATB2) gene at the 2q33.1 translocation breakpoint, while the 14q22.3 breakpoint was not intragenic. SATB2 mutation or deletion has been associated with both isolated and syndromic facial clefting; however, an association with TCS has not been reported. SATB2 functions broadly as a transcription regulator, and its expression patterns suggest an important role in craniofacial and central nervous system development, making it a plausible candidate gene for TCS.

In vitro and in vivo analysis of high flow nasal cannulae compared with nasal CPAP for newborns

Nasal continuous positive airway pressure (CPAP) has been shown to be effective in the treatment of newborn respiratory distress syndrome. However, there can be mechanical difficulties in maintaining a seal with the small newborn nose. Humidified high flow nasal cannulae have been introduced as an alternative method for positive distending pressure. In this issue of The Journal, Lampland et al from Children's Hospital of Minnesota have compared the two approaches both in vitro and in vivo. In vitro they showed that the high flow nasal cannulae system did not tolerate leaks as small as 30%, resulting in a loss of positive pressure.