Absent Radii Research Articles

Diyabetik Anne Bebeklerinde Nadir Görülen Bir Defekt: Radius Yokluğu

Diabetes mellitus (DM) is an important disease that negatively affects fetal development and women with pregestational diabetes have an increased risk for adverse pregnancy outcomes, including a markedly increased risk for birth defects. In this report, a newborn with absent radius associated with pregestational diabetes was presented. A male newborn was born at 40th gestational week from a 20-year-old mother by cesarean section. The patient had shortness in the limbs, hypoplastic right thumb and flexion contracture at his right hand besides respiratory distress.To our knowledge, with this case report, we would like to share the second case of diabetic mother’s infant with absent radius in the literature.

Prevalence and risk factors of radial ray deficiencies: A population-based case-control study.

Radial ray deficiency is the most common congenital deficiency of the upper limb. The aim of our study was to investigate maternal risk factors for radial ray deficiencies. We conducted a nationwide population-based case-control study using national registers. All cases with a radial ray deficiency born between 1996 and 2008 were included in the study and compared with five controls without limb deficiency. In total, 115 (10 isolated, 18 with multiple congenital anomalies, and 87 syndromic) cases with radial ray deficiencies were identified and compared with 575 matched controls. The total prevalence in Finland was 1.22 per 10,000 births. No significant risk factors were observed for nonsyndromic cases. In the syndromic group, advanced maternal age (≥35 years) increased the risk of radial aplasia (aOR 2.45, 95% CI 1.37-4.36), and a similar association was observed with multiple pregnancy (aOR 2.97, 1.16-7.62) and male sex (aOR 1.96, 1.18-3.25). Valproic acid was also a risk factor (p = .002). In conclusion, novel associations in the syndromic group of advanced maternal age and multiple pregnancy and increased risk of radial ray deficiencies were observed. Also, early reports on increased risk of RRD associated with valproate and male sex were supported by our results.

Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome

The thrombocytopenia and absent radii (TAR) syndrome is a rare disease associating bilateral radial agenesis and congenital thrombocytopenia. Here, we investigated in vitro megakaryocyte (MK) differentiation and expression of c-mpl in 6 patients. Using blood or marrow CD34(+) cells, the colony-forming unit (CFU)-MK number was markedly reduced. CD34(+) cells were also cultured in liquid medium in the presence of a combination of 3 cytokines (stem cell factor, interleukin-3, and interleukin-6) or megakaryocyte growth and development factor (PEG-rHuMGDF) with or without SCF. In the presence of PEG-rHuMGDF, the majority of mature megakaryocytes (CD41 high, CD42 high) underwent apoptosis. This phenomenon was also observed in cultures stimulated by three cytokines. However, this last combination of cytokines allowed a more complete terminal MK differentiation. Surprisingly, a homogeneous population of CD34(-)CD41(+)CD42(-) cells accumulated during the cultures. This population was unable to differentiate along the myeloid pathways. This result suggests that a fraction of MK cells is unable to differentiate in the TAR syndrome. We subsequently investigated whether this could be related to an abnormality in c-mpl. No mutation or rearrangement in the c-mpl gene was found by Southern blots or by sequencing of the c-mpl coding region and its promoter in any of the patients. Using Western blot analysis, a decreased level of Mpl was found in patient platelets. A decreased level of c-mpl messenger RNA in TAR platelets was also detected with a lower c-mpl-P to c-mpl-K ratio in comparison to adult platelets. Altogether, these results demonstrate that the thrombocytopenia of the TAR syndrome is associated with a dysmegakaryocytopoiesis characterized by cells blocked at an early stage of differentiation. (Blood. 2000;95:1633-1641)

Clinical Genetics and Dysmorphology: Our Extraordinary Experiences.

Abstract Background: We have previously described our extensive experiences with clinical genetic and dysmorphology in a plethora of publications. In a previous study, we reported 43 children with uncommon, rare and very rare genetic and hereditary disorders whom were observed during three-year period (2016-2018). In that series, very rare genetic, the case number 104 of Sanjad-Sakati-Richardson-Kirk syndrome in the world, the case number 130 of Townes Brocks syndrome and the case number 170 of Coffin Siris syndrome in the world. The aim of this paper is to describe our 2019 extraordinary new experiences with genetic disorders and dysmorphic syndromes. Material and methods: During the year 2019, 37 patients (25 males and 12 female) with genetic disorders and dysmorphic syndromes and were studied at the Children Teaching Hospital of Baghdad Medical City. Their ages ranged from 2 days to sixteen years. Results: Eight patients had Down syndrome (6 boys and 2 girls), 5 patients had Cornelia De Lang syndrome (4 boys and one girl), 2 male patients had Fragile X-syndrome, 2 male patients with Prader Willi syndrome, two patients had Noonan syndrome (a boy and girl), 2 brothers had Goldberg Shprintzen syndrome. Ten patients each had Facioscapulohumeral muscular dystrophy, Virchow Seckel Syndrome, Mowat Wilson syndrome, Toriello-Carey Syndrome, Ruprecht Majewski-Bosma syndrome, congenital myotonic muscular dystrophy (Congenital dystrophia myotonica), extended Michelin tire baby, Congenital absent radii without thumb aplasia, Dandy walker syndrome and the syndrome of congenital facial palsy and unilateral anotia. In addition, six children patients had newly recognized syndromes (five boys and one girl). Many of the patients in this series were previously described or reported. Conclusion: This one-year Iraqi pioneering experience in the fields of clinical genetics and clinical dysmorphology should herald the end of the Dark Age in these fields in Iraq.

Association of Radial Longitudinal Deficiency and Thumb Hypoplasia: An Update Using the CoULD Registry.

Deficiency of the radial aspect of the forearm and hand is the most common congenital longitudinal deficiency of the upper limb. Radial longitudinal deficiency is associated with several named syndromes. The purpose of the present study was to explore patterns of radial longitudinal deficiency and thumb hypoplasia in syndromes and to examine the severity of these differences across various syndromes. Data were collected from the Congenital Upper Limb Differences (CoULD) registry. Congenital differences are classified in the registry with use of the Oberg-Manske-Tonkin (OMT) classification system. Diagnosis of a syndrome by a physician as noted in the CoULD registry was recorded. Thumb deficiency and radial deficiency were classified according to the modified versions of the Blauth criteria and the Bayne and Klug criteria, respectively. We identified 259 patients with 383 affected limbs with radial deficiency. Eighty-three of these patients had a diagnosed syndrome. The severity of radial deficiency was correlated with the severity of thumb deficiency. The Kendall tau coefficient indicated significant correlation between radial severity and thumb severity (tau = 0.49 [95% confidence interval = 0.40 to 0.57]; p < 0.05). Subjects with a syndrome were twice as likely to have bilateral deficiency and 2.5 times more likely to have both radial and thumb deficiency compared with subjects without a syndrome. Subjects with VACTERL syndrome (vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula, renal anomalies, and limb defects) had patterns of thumb and radial deficiency similar to the general cohort, whereas subjects with Holt-Oram syndrome, TAR (thrombocytopenia absent radius) syndrome, and Fanconi anemia demonstrated varied presentations of thumb and radial deficiency. The present study investigated the characteristics of patients with radial longitudinal deficiency and thumb hypoplasia. Our results support the findings of previous research correlating the severity of radial deficiency with the severity of thumb deficiency. Furthermore, we identified characteristic features of patients with radial longitudinal deficiency and associated syndromes.

Expanding the phenotype of thrombocytopenia absent radius syndrome with hypospadias

Rare genetic diseases and syndromes may appear with unique features in some patients. In genetically-solved cases, this situation indicates a phenotypic expansion of the syndrome with additional features (i.e. the disease-associated gene gives rise to unusual clinical presentation). However, this situation can also hide a multilocus pathogenic variation that cannot be solved genetically except by a massive sequencing approach, such as exome sequencing. Here we describe the case of a child with bilateral radial aplasia, transient thrombocytopenia and anemia, cow's milk intolerance, hypospadias, facial dysmorphism, mild hypothyroidism and umbilical and inguinal hernia.Bilaterally absent radius, presence of thumbs and low platelet count are pathognomonic of thrombocytopenia absent radius (TAR) syndrome, but the child also showed other features beyond those reported in the literature. Since various diseases resembling the proband’s phenotype required differential diagnosis, clinical exome sequencing was performed. The results showed compound heterozygous mutations in the RBM8A gene, confirming the suspicion of TAR syndrome. A truncating heterozygous variant in the DUOX2 gene, known to be associated with transient thyroid dyshormonogenesis type 6 (TDH6), was also detected and may explain the proband's mild hypothyroidism.

Corrigendum: 1q21.1 deletion and a rare functional polymorphism in siblings with thrombocytopenia-absent radius-like phenotypes.

Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. We evaluated two siblings with TAR-like dysmorphology but lacking thrombocytopenia in infancy. Family NCI-107 participated in an IRB-approved cohort study and underwent comprehensive clinical and genomic evaluations, including aCGH, whole-exome, whole-genome, and targeted sequencing. Gene expression assays and electromobility shift assays (EMSAs) were performed to evaluate the variant of interest. The previously identified TAR-associated 1q21.1 deletion was present in the affected siblings and one healthy parent. Multiple sequencing approaches did not identify previously described TAR-associated SNPs or mutations in relevant genes. We discovered rs61746197 A > G heterozygosity in the parent without the deletion and apparent hemizygosity in both siblings. rs61746197 A > G overlaps a RelA-p65 binding motif, and EMSAs indicate the A allele has higher transcription factor binding efficiency than the G allele. Stimulation of K562 cells to induce megakaryocyte differentiation abrogated the shift of both reference and alternative probes. The 1q21.1 TAR-associated deletion in combination with the G variant of rs61746197 on the nondeleted allele is associated with a TAR-like phenotype. rs61746197 G could be a functional enhancer/repressor element, but more studies are required to identify the specific factor(s) responsible. Overall, our findings suggest a role of rs61746197 A > G and human disease in the setting of a 1q21.1 deletion on the other chromosome.

Radial Longitudinal Deficiency: Severity Differences Between U.S. and Japanese Cohorts

Radial longitudinal deficiency (RLD) presents on a spectrum of severity and associated diagnoses. The literature is limited in describing patient presentation without comparative data between countries. In a study comparing 2 cohorts of patients, 1 in the United States and 1 in Japan, we hypothesized that there would be a similar presentation of forearm deficiency severity, thumb hypoplasia severity, and associated syndromes between the 2 cohorts. Patients with RLD were identified via a comprehensive chart review at 2 pediatric hospital cohorts, 1 in the United States and 1 in Japan, capturing patients presenting over 15 years. We assessed RLD and thumb hypoplasia severity via a modified Bayne and Klug and modified Blauth classifications. The relationship between these 2 diagnoses and the presence of common medical conditions were evaluated and correlated. A total of 194 Japanese patients with 290 involved extremities were compared with 107 U.S. patients with 174 involved extremities. The U.S. cohort had a significantly more severe RLD, and a higher rate of bilaterality (63% vs 50%, respectively). A total of 131 Japanese patients (68%) and 41 U.S. patients (38%) had associated medical syndromes/associations, most frequently vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula and/or esophageal atresia, renal agenesis and dysplasia, and limb defects (VACTERL; 46 Japanese, 14 U.S.), Holt-Oram (44 Japanese, 5 U.S.), and thrombocytopenia absent radius syndrome (0 Japanese, 12 U.S.). Correlation analysis showed that increased RLD severity was associated with increased thumb hypoplasia severity in both groups, with 95% of modified Bayne and Klug III, IV, or V patients having severely affected thumbs (type IIIb, IV, or V). The U.S. patients had a more severe RLD and a higher rate of bilaterality. Japanese patients had a higher incidence of associated syndromes and radial polydactyly. Both cohorts showed that increased forearm severity was associated with more severe thumb hypoplasia. Differential diagnosis/symptom prevalence study III.

A rare developmental anomaly of the upper limb: Case of ulnar dimelia

Ulnar dimelia is a rare developmental anomaly, which is characterized by the duplication of ulna, absence of radius, and polydactyly. We report a case of a 5-year-old male child who was referred to our care with an extension deformity of the right elbow, loss of pronation and supination of the forearm, and flexion deformity with radial deviation of the ipsilateral wrist. Initially, we aimed to provide flexion of the elbow to improve his elbow function. The flexion was restricted to

P225 Carcinoid heart disease: report of a case in a patients with trombocytopenia absent radius

Abstract Background The carcinoid syndrome is characterized by extensive and several clinical manifestations. The diarrhea, the cutaneous flushing are the most frequents symptoms while cardiac manifestations (carcinoid heart disease) (CHD) occurs in a mean of 40%. Nowadays, the number of cases of CHD is lower than 20%, as a consequence of the widespread use of somatostatin analogues. At present, there is a mean delay in diagnosis of CHD of 1.5 years from the time of carcinoid syndrome detection. Hence, CHD is associated with a poor prognosis for clinical management. Case report We present a case of 45-years-old active woman, with Thrombocytopenia absent radius (TAR). This is characterized by a bilateral absence of the radio with the presence of both thumbs and thrombocytopenia. Our patient was attended for dyspnea of medium efforts, history of diarrhea, cutaneous flushing with tachycardia and elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) (89,6 mg/24 (2,0-9,0)). The Transthoracic echocardiography showed morphologic changes that affected the tricuspid valve: diminished curvature of the leaflets, altered dynamic motion of the leaflets during diastole, fused and shortened chordae retraction and reduced excursion of the valve. A moderate to severe tricuspid regurgitation and tricuspid stenosis with gradient media de 5 mmHg was observed. In addition, the right ventricle was dilated, a severe pulmonary hypertension, a right pleural effusion and a minor pericardial effusion circumference were detected. All these findings were consistent with CHD. Conclusions This report describes an unusual case of CHD in TAR patient. In fact, the interest of this case is the role played by the echocardiogram in the differential diagnosis for tricuspid valve diseases. Tricuspid stenosis is an infrequent condition and it is usually related with rheumatic disease associated with mitral valve disease. Although the carcinoid syndrome is infrequent, any changes in the anatomical structure of the tricuspid valve (thickening, fibrosis and rigidity associated with stenosis and tricuspid regurgitation) should alert us to the suspicion of CHD Abstract P225 Figure.

Rare Syndrome of Thrombocytopenia Absent Radius Diagnosed Prenatally in a Female Fetus

Background: Exposure to adverse conditions during the period of intrauterine development can lead to lifelong consequences. In this sense, evidence has pointed to an important influence of maternal variables, such as pre-gestational body mass index (BMI) and gestational weight gain (GWG), on the health of the offspring in adolescence, increasing the risk of obesity and damage to the cardiometabolic profile. Methods and Findings: This is a cross-sectional study in a cohort of 49 adolescents. The following variables were collected with adolescents in a scheduled consultation: sociodemographic (sex and age), clinical (diastolic and systolic blood pressure), anthropometric (weight, height, BMI and waist circumference [WC]), biochemical (glucose, total cholesterol, LDL-c, HDL-c, triglycerides and leptin) and birth (birth weight and gestational age). In addition, gestational variables (pregestational weight and height, pre-gestational BMI, GWG, and type of delivery) were collected in an interview with the mothers of the young people. For statistical analysis, adolescents were stratified according to sex. A correlation between BMI and WC was observed in adolescence with pre-gestational weight and BMI only in boys (r=0.906; p=0.001, r=0.878; p=0.002/ r=0.909; p=0.001, r=0.865; p=0.003). Moreover, in males, triglycerides correlated with pre-gestational BMI (r=0.712, p=0.048), and LDL-c with GWG (r=0.699, p=0.024). Serum leptin concentration correlated with pre-gestational weight and BMI in girls (r=0.532, p=0.006; r=0.440, p=0.028) and, in boys, with GWG (r=0.901, p=0.037). Results: In view of the results, it is suggested that gestational anthropometric variables can influence the BMI, WC and biochemical variables of the offspring in a gender-dependent way, largely affecting boys.

Thrombocytopenia Absent Radius Syndrome: Rare Cause of Constitutional Thrombocytopenia

Thrombocytopenia Absent Radius Syndrome: Rare Cause of Constitutional Thrombocytopenia

Congenital absent radii without thumb aplasia: the first case in Iraq and the early documentation of the condition in the literature

Background: The vast majority of the reported cases of congenital absent radii without thumb aplasia were associated with congenital thrombocytopenia or thrombocytopenia occurring early life. The occurrence of congenital absent radii without thumb aplasia and without evidence congenital thrombocytopenia or thrombocytopenia occurring early life is extremely rare and has not been reported in Iraq. Patients and methods: An Iraqi newborn infant with congenital absent radii without evidence of congenital thrombocytopenia during the first week is presented, and the relevant literatures were reviewed with aim of describing the early documentation of the condition in the medical literature. Results: A newborn infant with congenital absence of the radii without thumb aplasia. The neonate was followed for one week without the occurrence of thrombocytopenia. The rest of physical examination was normal and no other abnormalities could be detected. The parents were consanguineous, but family history was negative for a similar condition. Conclusion: The extremely rare occurrence congenital absence of the radii without thumb aplasia without evidence of thrombocytopenia during the first week of life is reported in an Iraqi newborn.

Phenotypic Overlap of Roberts and Baller-Gerold Syndromes in Two Patients With Craniosynostosis, Limb Reductions, and ESCO2 Mutations

Baller-Gerold (BGS, MIM#218600) and Roberts (RBS, MIM#268300) syndromes are rare autosomal recessive disorders caused, respectively, by biallelic alterations in RECQL4 (MIM*603780) and ESCO2 (MIM*609353) genes. Common features are severe growth retardation, limbs shortening and craniofacial abnormalities which may include craniosynostosis. We aimed at unveiling the genetic lesions underpinning the phenotype of two unrelated children with a presumptive BGS diagnosis: patient 1 is a Turkish girl with short stature, microcephaly, craniosynostosis, seizures, intellectual disability, midface hemangioma, bilateral radial and thumb aplasia, tibial hypoplasia, and pes equinovarus. Patient 2 is an Iranian girl born to consanguineous parents with craniosynostosis, micrognathism, bilateral radial aplasia, thumbs, and foot deformity in the context of developmental delay. Upon negative RECQL4 test, whole exome sequencing (WES) analysis performed on the two trios led to the identification of two different ESCO2 homozygous inactivating variants: a previously described c.1131+1G>A transition in patient 1 and an unreported deletion, c.417del, in patient 2, thus turning the diagnosis into Roberts syndrome. The occurrence of a Baller-Gerold phenotype in two unrelated patients that were ultimately diagnosed with RBS demonstrates the strength of WES in redefining the nosological landscape of rare congenital malformation syndromes, a premise to yield optimized patients management and family counseling.

A case of Cows' milk allergy in the syndrome of thrombocytopenia with absent radius

No abstract available

21-week pregnancy with trisomy 18 (Edwards syndrome) − bone malformations highlighted

Edwards syndrome, also known as Trisomy 18 (T18) or Trisomy E, is a genetic disorder caused by the presence of all or part of an extra 18th chromosome. Some physical malformations associated with Edwards syndrome include small head (microcephaly) accompanied by a prominent back portion of the head (occiput); low-set, malformed ears; abnormally small jaw (micrognathia); cleft lip/cleft palate; upturned nose; narrow eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); drooping of the upper eyelids (ptosis); a short breast bone; clenched hands; choroid plexus cysts; underdeveloped thumbs and or nails, absent radius, webbing of the second and third toes; clubfoot; and in males, undescended testicles. The diagnosis of Trisomy 18 is by ultrasound and amniocentesis, the fetal DNA being examined for genetic abnormalities. Therapeutic abortion can be done.

Experimental evidence that preaxial polydactyly and forearm radial deficiencies may share a common developmental origin.

Preaxial polydactyly is a congenital hand anomaly predominantly of sporadic occurrence, which is frequently associated with abnormalities of the Sonic hedgehog signalling pathway. In experimentally induced preaxial polydactyly, radial aplasia is also frequently observed. To determine if there is a correlation between preaxial polydactyly and radial aplasia, we induced ectopic Sonic hedgehog signalling during chicken limb development with application of a smoothened-agonist (SAG) or retinoic acid. Application of SAG caused malformations in 71% limbs including preaxial polydactyly (62%) and forearm abnormalities (43%). Retinoic acid application induced malformations in 56% of limb including preaxial polydactyly (45%) and forearm abnormalities (50%). Radial dysplasia and ulnar dimelia were observed in both experimental conditions. We demonstrate that ectopic Sonic hedgehog signalling may cause both preaxial polydactyly and predictable forearm anomalies and that these conditions could potentially be classified as one embryological group. We propose a unifying model based on known models of ectopic Sonic hedgehog signalling.

Thrombocytopenia with absent radii (TAR) Syndrome in a male child: report of a rare case

Introduction: Thrombocytopenia with absent radii (TAR) Syndrome is a rare congenital defect presents with hypomegakaryocytic thrombocytopenia and bilateral radial aplasia and preserved thumb.Case presentation: A three and half year’s old male baby born out of non-consanguineous marriage with thrombocytopenia and bilateral absence of radius. Such type of anomaly has been previously reported in the children of a non- consanguineous marriage was few.Conclusions: Though rare incidence, all thrombocytopenia with any skeletal deformity cases in newborn or infancy to toddler age group must be thoroughly investigated to exclude TAR syndrome. Case is presenting here because of rarity.International Journal of Human and Health Sciences Vol. 02 No. 02 April’18. Page : 91-93

Screening practices and associated anomalies in infants with anorectal malformations: Results from the Midwest Pediatric Surgery Consortium

BackgroundThis study evaluates screening practices and the incidence of associated anomalies in infants with anorectal malformations (ARM). MethodsWe performed a multi-institutional retrospective cohort study of children born between 2007 and 2011 who underwent surgery for ARM at 10 children's hospitals. ARM type was classified based on the location of the distal rectum, and all screening studies were reviewed. ResultsAmong 506 patients, the most common ARM subtypes were perineal fistula (40.7%), no fistula (11.5%), and vestibular fistula (10.1%). At least 1 screening test was performed in 96.6% of patients, and 11.3% of patients underwent all. The proportion of patients with ≥1 abnormal finding on any screening test varied by type of ARM (p<0.001). Screening rates varied from 15.2% for limb anomalies to 89.7% for renal anomalies. The most commonly identified anomalies by screening category were: spinal: tethered cord (20.6%); vertebral: sacral dysplasia/hemisacrum (17.8%); cardiac: patent foramen ovale (58.0%); renal: hydronephrosis (22.7%); limb: absent radius (7.9%). ConclusionScreening practices and the incidence of associated anomalies varied by type of ARM. The rate of identifying at least one associated anomaly was high across all ARM subtypes. Screening for associated anomalies should be considered standard of care for all ARM patients. Type of studyMulti-institutional retrospective cohort study. Level of evidenceIII

Association of VACTERL with truncus arteriosus, left-sided aortic arch, hypoplastic pulmonary arteries, and severe radial axis defect

Background: VACTERL association is usually a sporadic disorder, the possible etiologies of which have been proposed as familial as well as multiple genetic and environmental factors. VACTERL association usually consists of at least three of the core features of vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. Vertebral anomalies, cardiac malformations, renal anomalies, and limb malformations have been reported to occur in 60-80%, 40-80%, 50-80%, and 40-50% of the patients, respectively. Among the cardiac anomalies, ventricular septal defect is the most prevalent one. Truncus arteriosus is a rarely associated defect. The radial anomalies are the most classic limb defects with different severity levels (types I-IV). Although radial axis defect usually accompanies this association, complete absence of radius is reported only in one third of the cases. Case report: In this case study, we reported a neonate having this association consisting of severe cyanotic congenital heart defect (truncus arteriosus) and unilateral type IV radial aplasia. Conclusion: VACTERL association components can have various new findings.