Nasal Bone Hypoplasia Research Articles

Residual risk of clinically significant copy number variations in fetuses with nasal bone absence or hypoplasia after excluding non-invasive prenatal screening-detectable findings

BackgroundIt remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes. MethodsThis prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes. ResultsThe overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028). ConclusionsThe residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.

Shortened fetal long bones: A notable intrauterine phenotypic feature in SHOX-associated skeletal dysplasia.

To explore the intrauterine phenotypic spectrum of short stature homeobox-containing (SHOX) gene-associated skeletal dysplasia and provide genetic counseling at-risk pregnancies. We analyzed the fetuses with SHOX-microdeletions identified by single nucleotide polymorphism (SNP)-array. The intrauterine phenotypes and outcomes were further elaborated. Nine fetuses carrying a single SHOX-microdeletion were reported, with deletion sizes ranging from 0.134 to 1.35 Mb. Shortened long bones were observed in all fetuses, varying from -2.0 standard deviation (SD) to -5.3 SD. Moreover, all cases had a femur length/foot ratio less than 0.87 and a femur/abdominal circumference ratio greater than 0.16, suggesting that non-lethal skeletal dysplasia may be involved. Two fetuses showed intrauterine growth restriction, and two had nasal bone hypoplasia. Prenatal ultrasonography did not reveal other obvious anomalies, including the Madelung deformity. Five microdeletions were inherited and one was de novo. Five terminations and four newborns were recorded. Two newborns had normal stature, and two were short-statured (height <3rd percentile), with one having inflexible wrists. SHOX haploinsufficiency may manifest with shortened fetal long bones. The combination of history taking, prenatal ultrasonography, and SNP-array can prompt early prenatal diagnosis and timely postnatal treatment of SHOX-associated skeletal dysplasia.

Single nucleotide polymorphism array (SNP-array) analysis for fetuses with abnormal nasal bone.

This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

Assessing the value of second-trimester nasal bone hypoplasia in predicting chromosomal abnormalities: a retrospective chromosomal microarray analysis of 351 fetuses.

To evaluate the value of fetal nasal bone hypoplasia and other prenatal risk factors in predicting chromosomal abnormalities. In this retrospective cohort study, we collected data on singleton pregnancies diagnosed with fetal nasal bone hypoplasia during second-trimester ultrasound. Fetal karyotyping and chromosomal microarray analysis (CMA) were performed, and pregnancy outcomes were assessed. The association between fetal nasal bone hypoplasia and chromosomal abnormalities was evaluated according to whether other prenatal risk factors were observed. Our final analysis included 351 pregnancies, of which 62 (17.7%) fetuses had chromosomal abnormalities, including 36 cases of trisomy-21, six cases of trisomy-18, one case each of trisomy-13, and 47, XYY syndrome, and 18 cases of copy number variations (CNVs). Among the 243 cases of isolated nasal bone hypoplasia, 28 (11.5%) cases of chromosomal aberrations were identified. The incidence was significantly higher if other soft markers or structural abnormalities were simultaneously detected. Pregnancy was terminated in 43 aneuploid fetuses and nine fetuses detected with CNVs. The parents of the fetuses diagnosed with 47, XYY syndrome and the other nine CNVs chose to continue the pregnancy, and no abnormalities were detected in the newborns. Furthermore, we found that other prenatal risk factors should be considered in evaluating the likelihood of chromosomal abnormalities in fetuses with nasal bone hypoplasia. Nasal bone hypoplasia is a highly specific soft marker that is associated with multiple chromosomal abnormalities. The risk of chromosomal abnormalities increases when combined with structural abnormalities or increased nuchal translucency (NT). Chromosomal microarray analysis is a powerful prenatal test for chromosomal abnormalities, which may be warranted in fetuses with nasal bone hypoplasia.

Cases of tetrasomy 9p and trisomy 9p in prenatal diagnosis-Analysis of noninvasive and invasive test results.

Objective: Tetrasomy 9p and trisomy 9p are rare chromosomal aberrations. The phenotypes of tetrasomy 9p and trisomy 9p are variable. Most cases are diagnosed in the postnatal period. The study aims to analyze the prenatal phenotype of tetrasomy 9p and trisomy 9p in terms of ultrasound and screening tests. Methods: A set of 1573 prenatal tests performed from 2016 to 2021 was reviewed to identify all cases with trisomy 9p and tetrasomy 9p. In four cases with 9p gain, non-invasive and invasive test results were analyzed. Results: Four cases with the 9p gain were diagnosed in the prenatal period: two cases with tetrasomy 9p and two cases with trisomy 9p. Nasal bone hypoplasia and ventriculomegaly are common features of 9p gain. In two out of four cases with the 9p gain, an increased risk of trisomy 21 was found in the combined first-trimester screening test. Conclusion: Trisomy 9p and tetrasomy 9p are characterized by a variable phenotype in the prenatal period, manifesting in genetically abnormal fetuses. The tetrasomy 9p and trisomy 9p may suggest trisomy 21 in the first trimester.

Fetal Nasal Bone Hypoplasia in the Second Trimester as a Marker of Multiple Genetic Syndromes.

Nasal bone hypoplasia is associated with a trisomy of chromosome 21, 18 or 13. Nasal bone hypoplasia can also be seen in other, rarer genetic syndromes. The aim of the study was to evaluate the potential of nasal bone hypoplasia, in the second trimester of pregnancy, as a marker of fetal facial dysmorphism, associated with pathogenic copy number variation (CNV). This retrospective analysis of the invasive tests results in fetuses with nasal bone hypoplasia, after excluding those with trisomy 21, 18 and 13. In total, 60 cases with nasal bone hypoplasia were analyzed. Chromosomal aberrations were found in 7.1% of cases of isolated nasal bone hypoplasia, and in 57% of cases of nasal bone hypoplasia with additional malformations. Additionally, in four of nine cases with non-isolated nasal bone hypoplasia but normal CMA results, a monogenic disease was diagnosed. Non-isolated hypoplastic nasal bone appears to be an effective objective marker of fetal facial dysmorphism, associated with pathogenic CNVs or monogenic diseases. In isolated cases, chromosomal microarray testing can be of additional value if invasive testing is performed, e.g., for aneuploidy testing after appropriate counseling.

Пренатальная диагностика врожденной дисфункции коры надпочечников

Enlarged nuchal translucency and nasal bone hypoplasia are considered as markers of chromosomal abnormalities and fetal malformations, although enlarged nuchal translucency can be detected in a healthy fetus and completely disappear by 14–15 weeks’ gestation and can also be observed when the karyotype is normal (in antenatal fetal death, congenital heart disease, miscarriage, preterm birth). The study of markers of chromosomal abnormalities is of practical interest in terms of accumulating information and gaining experience in using them for prenatal diagnosis. A case of accurate sex determination in the fetus with salt-wasting form of congenital adrenal hyperplasia and virilization of the external genitalia (Prader grade IV) at birth is presented. Highly effective prenatal screening including amniocentesis and karyotyping (46XX) at 13 weeks’ gestation ensured that pediatricians were prepared for timely prescription of gluco- and mineralocorticoid replacement therapy. This enabled to prevent the development of acute adrenal crisis and choose adequate management tactics, thereby providing normal puberty and potential fertility. Key words: congenital adrenal hyperplasia, prenatal screening, enlarged nuchal translucency

Is Prenatal Diagnosis Necessary for Fetal Isolated Nasal Bone Absence or Hypoplasia?

PurposeThis study aimed to explore the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal isolated nasal bone absence (INBA) or isolated nasal bone hypoplasia (INBH). We hope to provide additional relevant information for clinical counseling.Patients and MethodsFrom November 1, 2018, to March 1, 2020, 55 pregnant women with isolated nasal bone dysplasia were admitted to the Changzhou Maternity and Child Health Care Hospital. Based on the degree of abnormality, the patients were divided into two groups: INBA and INBH. CMA was performed on all patients. The clinical data and prenatal genetic diagnoses of the two groups were retrospectively analyzed. According to the requirements of WES for samples, 12 cases with negative CMA results were selected for the WES test.ResultsA total of 55 cases with INBA or INBH met the inclusion criteria. In 35INBA fetuses, there was one case of trisomy 21 and one case of 10q11.22 deletion (5.7Mb), and the abnormality rate was 5.71% (2/35). Compared with INBA fetuses, the abnormality rate was increased in the fetuses with INBH [15.00% (3/20)] (15.00% vs 5.71%); there was one case of 1q21.1 duplication (1.3Mb), one case of Xp22.31 duplication (1.67Mb), and one case of 4p deletion (7.6Mb). In a later retrospective study, two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively.ConclusionA preliminary study confirmed that molecular prenatal diagnosis should be performed in fetuses with INBA or INBH. CMA followed by WES is an effective method.

Chromosomal Microarray Analysis for the Prenatal Diagnosis in Fetuses with Nasal Bone Hypoplasia: A Retrospective Cohort Study.

BackgroundPrevious studies have shown a strong correlation between fetal nasal bone hypoplasia and chromosomal anomaly; however, there is little knowledge on the associations of fetal nasal bone hypoplasia with chromosomal microdeletions and microduplications until now. Chromosomal microarray analysis (CMA) is a high-resolution molecular genetic tool that is effective to detect submicroscopic anomalies including chromosomal microdeletions and microduplications that cannot be detected by karyotyping. This study aimed to examine the performance of CMA for the prenatal diagnosis of nasal bone hypoplasia in the second and third trimesters.Subjects and MethodsA total of 84 pregnant women in the second and third trimesters with fetal nasal bone hypoplasia, as revealed by ultrasound examinations, were enrolled, and all women underwent karyotyping and CMA with the Affymetrix CytoScan 750K GeneChip Platform. The subjects included 32 cases with fetal nasal bone hypoplasia alone and 52 cases with fetal nasal bone hypoplasia combined with other ultrasound abnormalities, and the prevalence of genomic abnormality was compared between these two groups.ResultsKaryotyping detected 21 cases of chromosomal anomaly in the 84 study subjects (21/84, 25%), including trisomy 21 (14 cases), trisomy 18 (3 cases), 46, del (4)(p16) karyotype (2 cases), 47, XYY syndrome (1 case) and 46, XY, del (5) (p15) karyotype (1 case). CMA detected additional four fetuses with pathogenic copy number variations (CNVs) and six fetuses with uncertain clinical significance (VOUS). No significant difference was detected in the prevalence of genomic abnormality in fetuses with nasal bone hypoplasia alone and in combination with other ultrasound abnormalities (13/32 vs 18/52; χ2 = 0.31, P > 0.05). The pregnancy was terminated in 21 fetuses detected with chromosomal abnormality and 4 fetuses detected with pathogenic CNVs. Among the other six fetuses detected with VOUS, the parents chose to continue the pregnancy, and the newborns all had normal clinical phenotypes.ConclusionIn addition to chromosomal abnormalities identified in 21 fetuses by karyotyping, CMA detected additional 10 fetuses with abnormal CNVs (10/84, 11.9%) in the study population. CMA is a promising powerful tool for prenatal diagnosis that may provide valuable data for the accurate assessment of fetal prognosis and the decision of pregnancy continuation during the prenatal clinical counseling.

Is Noninvasive Prenatal Screening Appropriate for Pregnant Women Age 35 or Older In Cases if Isolated Fetal Nasal Bone Abnormalities in The Chinese Han Population?

BackgroundEthnic background may affect the prevalence of nasal bone absence and the length of the nasal bone. This study aimed to elucidate the significance of absent or hypoplastic fetal nasal bone in the Chinese Han population and to formulate an optimal management plan for patients age 35 or older in cases of isolated abnormal fetal nasal bone.Material/MethodsWe prospectively assigned pregnant women whose fetuses had nasal bone absence or hypoplasia to separate groups according to their choice for noninvasive prenatal screening (NIPS) between January 1, 2013, and December 31, 2018. Demographic data, ultrasound findings, results of conventional maternal serum screening and NIPS, fetal karyotype, pregnancy outcomes, and expenses associated with prenatal testing were recorded. The incidence and odds ratio of nasal bone abnormality and the sensitivity and specificity of different prenatal genetic screening tests were calculated.ResultsA total of 1946 cases with fetal nasal bone absence or hypoplasia were included. Cases of isolated nasal bone abnormality (1736 cases) were divided into the NIPS group (Gr 1, n=429) and the non-NIPS group (Gr 2, n=1307). Sixty-four cases involved chromosomal abnormality. The sensitivity, specificity, and positive and negative predictive values of NIPS in Gr 1 were 100%, 100%, 100%, and 100%, respectively. The odds ratio of fetal chromosomal abnormalities for isolated fetal nasal bone abnormalities when maternal age was ≥35 was 4.615 (95% CI: 1.592–13.381). The cost-effectiveness ratio of contingent screening (NIPS first) was significantly lower than amniocentesis directly.ConclusionsThe nasal bone provides an important marker for chromosome abnormalities in some populations, but to a lesser extent in the Chinese Han population. NIPS is an excellent first option for follow-up among pregnant women age ≥35 in cases of absent or hypoplastic fetal nasal bone in the first trimester ultrasound scan.

Role of Second-Trimester Soft Markers for Screening of Down Syndrome

Down syndrome is clinically characterized by mental retardation, birth defects, and specific physical features that are identifiable at birth. Mental retardation ranges from mild to severe with most cases showing a moderate level, to evaluate the effectiveness the second-trimester soft marker sonography combined with biochemical quadriple test screening for prenatal diagnosis of triosmy 21 in patient with risk factor for down syndrome, this is a prospective cohort study that was conducted at Department of obstetrics & Gynecology ,at Benha university hospital, and carried on 80 patients ,Ultrasound was done by voluson 2d and 3d searching for a number of soft markers, that there is high significant correlation between down syndrome and Hyper echogenic fetal bowel, Nasal bone hypoplasia, Mild ventriculomegally and Enlarged cysterna magna. Also there is significant correlation between Down syndrome and Choroid plexus cyst, Intra-cardiac echogenic foci, Single umbilical artery and Mild hydronephrosis, Second‐trimester soft markers, especially a thickened nuchal fold, remain important observations in the detection of Down syndrome by sonography among fetuses who have had first‐trimester sonographic screening for aneuploidy.

Evaluation of fetal nasal bone length during 18&lt;sup&gt;+0&lt;/sup&gt;-23&lt;sup&gt;+6&lt;/sup&gt; gestational weeks

Purpose: To establish the nomograms of fetal nasal bone length reported the ethnic differences and relationship between chromosomal abnormalities, between 18+0-23+6 gestational weeks.Material and Method: In this study, 2653 fetus between 18+0-23+6 gestational weeks had normal US findings and had not postnatal anomaly were retrospectively evaluated between January 2009 and September 2014. After detailed fetal anomaly scan, biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), nasal bone (NB) length and mean gestational weeks (GW) of each fetus were recorded. Regression analyses were performed between NB length and GW, BPD, HC, AC and FL. The reference values for 5-10-25-50-75-90-95. percentiles were established for each gestational week.Results: In this study, 27 twin pregnancies were detected in the 2626 pregnant women (age range, 17–46 years; mean age, 30.02 ±5.78 years). There were 159, 214, 528, 599, 563, 583 fetuses and the mean NB lengths were 5.5 ± 0.85, 6.3 ± 0.83, 6.6 ± 0.81, 6.9 ± 1, 7.1 ± 0.86, 7.6 ± 0.89 (minimum 4 mm and maximum 10.1 mm) between 18+0-23+6 gestational weeks, respectively. NB length was increased linearly consistent with GH, BPD, HC, AC and FL during 18+0-23+6 gestational weeks. In correlation analysis, the fetal NB length were significantly correlated with GW, BPD, HC, AC and FL (p<0.001).Conclusion: In our study, we established the NB length nomogram in healthy fetuses between 18+0-23+6 gestational weeks. We think that this reference values can be used for diagnosis of nasal bone hypoplasia in prenatal screening.

Reconstruction of the Congenital Nasal Bone Hypoplasia with Rib Cartilage Graft: Aesthetic, Functional and Psychological Asp

Reconstruction of the Congenital Nasal Bone Hypoplasia with Rib Cartilage Graft: Aesthetic, Functional and Psychological Asp

Nasal bone to nasal tip length ratio for describing nasal bone hypoplasia and predicting trisomy 21.

IntroductionFetal nasal bone hypoplasia has been proven to be a strong marker for trisomy 21 during second trimester ultrasonography. Rather than evaluating the nasal bone hypoplasia according to the nomograms, it may be possible to evaluate it with a more practical and specific method.Material and methodsRetrospectively collected data were provided from the saved and stored patient data between 2012 and 2017. Nasal bone length and nasal tip length were measured and the ratio was calculated. The ratio ≤ 1/3 was defined as the threshold ratio for the definition of the marker. Nasal bone nasal tip length (NB/NL) ratio values were compared among groups with trisomy 21 and euploid fetuses.ResultsA total of 59 fetuses had trisomy 21 and 2304 euploid fetuses were included in the study. The ratio of nasal bone to nasal tip length was 1/3 and below in 21/59 (35.5%) of fetuses with trisomy 21 whereas this ratio was 31/2304 (1.3%) in euploid fetuses. The difference was statistically significant (p < 0.001). Sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of nasal bone/nasal tip ratio ≤ 1/3 were 35.5%, 98.6%, 26.4 and 0.6 for Down syndrome, respectively.ConclusionsThis study suggested that the nasal bone to nasal tip length ratio may be a new promising and practical sonographic marker in the second trimester genetic sonography. Although its sensitivity is not high, it seems to be more practical and specific than the evaluation of fetal nasal bone length.

Rhinoplasty in a Patient with Nasal Bone Hypoplasia: A Case Report

Rhinoplasty in a Patient with Nasal Bone Hypoplasia: A Case Report

Application of chromosomal analysis for 29 cases of fetuses with nasal bone absence or hypoplasia

Objectives: To explore the chromosomal analysis for fetuses with nasal bone absence or hypoplasia. Methods: This was a retrospective study on 29 pregnancies nasal bone absence or hypoplasia which underwent prenatal diagnosis, including chorionic villi (CV), amniotic fluid or cordocentesis.The indication of the procedures and results were evaluated. Result: Fifteen (51.7%, 15/29) of chromosome abnormities were diagnosed with indication of fetal nasal bone absence or hypoplasia, including eight with trisomy 21, two with trisomy 13, two with X chromosome aneuploidy and three with pathogenic copy number variations (CNVs) respectively.The incidence of chromosomal abnormalities in fetus with nasal bone hypoplasia (2/5, 40%) was lower than that in fetus with nasal bone absence (13/29, 54.2%). The incidence of chromosomal abnormalities in fetus with non-syndromic nasal bone absence or hypoplasia (4/13) was lower than that in fetus with syndromic nasal bone absence or hypoplasia (11/16). Conclusion: The incidence of chromosomal abnormalities in fetus with nasal bone absence or hypoplasia was higher and prenatal diagnosis was recommended for all types of the disease.For the fetus with nasal bone absence or hypoplasia, it is recommended to give priority to CNVs for prenatal diagnosis.

Lejeune / “cat's cry” syndrome: prenatal ultrasound findings

The article describes a case of the prenatal diagnosis of Lejeune syndrome in 19 weeks 6 days of gestation. The following sonographic findings were identified: broad bridge, snub nose, hypoplasia of nasal bones and mandible, hypoplasia of the cavity of pellucid septum, ventriculomegaly. The patient was given 46,XX,del(5)(P12)[18] prenatal karyotyping. The family was consulted by the Regional Prenatal Board. The pregnancy was terminated by the family decision. The phenotype characteristics and congenital malformations discovered with the prenatal diagnosis were being then confirmed in the postmortem examination.

Fetal nasal bone hypoplasia in the second trimester and risk of abnormal karyotype in a population of Chinese pregnant women

Fetal nasal bone hypoplasia in the second trimester and risk of abnormal karyotype in a population of Chinese pregnant women

Cleft Lip Case in a Middle Bronze Age Young Man from Altai, Russia

Oral cleft (OC) is a common congenital anomaly in humans, which occurs in approximately one per 700 live births. However, cleft skulls are found relatively seldom in archaeological specimens, especially for the bc period. Mortality of infants with OC was apparently high because of breastfeeding difficulties and culturally sanctioned rejection of them in the past. This paper presents one of the most ancient cases of OC in Eurasia. The finding comes from the Middle Bronze Age pastoralists' cemetery in Altai, Russia. The skeletal remains have been radiocarbon dated to 1883–1665 cal bc. Cranial and dental measurements, computed tomography and radiography have been used to examine this malformation. The facial sculpting reconstruction has been performed to visualise the ante mortem appearance of the cleft face. Besides, δ13C and δ15N isotope analysis was used for a comparative study of the diet of the cleft individual. It has been established that a young man from Altai was affected by complete bilateral cleft lip and alveolus, which is a very rare form of typical OC. This defect is associated with dental anomalies such as hypodontia, microdontia, and ectopia as well as with dysmorphology of the facial complex outside the cleft area, including mild hypertelorism, hypoplasia of nasal bones and antheroposterior maxillary deficiency. Furthermore, aplasia of the frontal sinuses and the sacral spina bifida occulta have been observed. These findings are consistent with clinical data indicating strong correlation between development of a major defect and multiple minor anomalies. The results of the study also suggest that there was tolerant attitude towards the facial deformities among the ancient Altai pastoralists. Copyright © 2016 John Wiley & Sons, Ltd.