Verma-Naumoff syndrome: a case report / Síndrome de Verma-Naumoff: a propósito de un caso

In skeletal dysplasias, there are short rib polydactyly syndromes, which traditionally differentiate into four lethal types. This report describes a case of Type III, which presented characteristics of Types I and II. A 38-year-old woman presented fetal growth restriction at 17 weeks and 6 days, decreased amniotic fluid, enlarged and hyperechogenic kidneys, and long bones below the 3rd percentile. Three weeks later, she developed anhydramnia. The couple did not consent to the performance of an invasive test for genetic diagnosis and chose to maintain the pregnancy. At 33 weeks, due to premature labor and interactivity, a cesarean section was performed, giving birth to a female baby, who died due to respiratory failure there were no vocal cords and no trachea visible at laryngoscopy. On physical examination, he had the phenotypic characteristics of the syndrome. An X-ray showed short ribs and severe pulmonary hypoplasia. After birth, the parents chose not to carry out a genetic study or an anatomical examination. Researchers have suggested that there is an intersection of the anatomical changes of the types. This case report supports this theory.

En las displasias esqueléticas, existen síndromes de polidactilia de costillas cortas, que tradicionalmente se diferencian en cuatro tipos letales. Este reporte describe un caso del tipo III, que presentó características de los tipos I y II. Mujer de 38 años con restricción del crecimiento fetal a las 17 semanas y 6 días, líquido amniótico disminuido, riñones agrandados e hiperecogénicos y huesos largos por debajo del percentil 3. Tres semanas después, desarrolló anhidramnia. La pareja no consintió en la realización de una prueba invasiva de diagnóstico genético y optó por mantener el embarazo. A las 33 semanas, debido al parto prematuro y la interactividad, se realizó una cesárea, dando a luz a un bebé, que murió debido a una insuficiencia respiratoria: no había cuerdas vocales ni tráquea visible en la laringoscopia. Al examen físico presentaba las características fenotípicas del síndrome. Una radiografía mostró costillas cortas e hipoplasia pulmonar severa. Después del nacimiento, los padres optaron por no realizar un estudio genético ni un examen anatómico. Los investigadores han sugerido que existe una intersección de los cambios anatómicos de los tipos. Este reporte de caso apoya esta teoría.

Polidactilia poliaxial. Presentación de casos

RESUMEN La polidactilia es una anomalía congénita caracterizada por la existencia de dedos supernumerarios o bífidos. Esta puede presentarse aislada o asociada a otras malformaciones formando parte de algunos síndromes conocidos. El presente trabajo tiene como objetivo mostrar los resultados quirúrgicos de dos pacientes en edad pediátrica que tuvieron mayor grado de complejidad, de raza negra africana, los cuales presentaban polidactilia y fueron operados por galenos cubanos en la ciudad de Gaborone, en Botswana. Los dos pacientes tenían patrón de herencia autosómica dominante. El tratamiento quirúrgico logró armonía y simetría en miembros superiores e inferiores con buenos resultados estéticos y funcionales.

ABSTRACT Polydactyly is a congenital anomaly characterized by the existence of supernumerary or bifid fingers. This can occur isolated or associated with other malformations as part of some known syndromes. The objective of this research is to show the surgical results of two pediatric patients with a higher degree of complexity, black Africans, who presented polydactyly and were operated on by Cuban doctors in Gaborone city, Botswana. Both patients had an autosomal dominant pattern of inheritance. Surgical treatment achieved harmony and symmetry in upper and lower limbs with good aesthetic and functional results.

Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome type Ⅲ / 中华围产医学杂志

This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.

DYNC2H1 gene mutation analysis and prenatal diagnosis in two pedigrees affected with short rib-polydactyly syndrome type Ⅲ / 中华围产医学杂志

Objective:To investigate the molecular genetic etiology of two fetuses with short rib-polydactyly syndrome type Ⅲ (SRPS Ⅲ).Methods:Next-generation sequencing (NGS) was used to detect 226 known genes related to inherited skeletal dysplasia in two fetuses with SRPS Ⅲ diagnosed in the First Affiliated Hospital of Zhengzhou University in August 2015 and June 2020. Suspect pathological variants were verified in the pedigree members using Sanger sequencing. The prenatal genetic diagnosis of the high-risk fetus in pedigree one was conducted to identify the confirmed pathogenic variation.Results:The homozygous mutation of DYNC2H1 gene c.5881A>G(p.Lys1961Glu) was identified in the proband in pedigree one, and the parents were the carriers. The proband in pedigree two carried compound heterozygous mutations in the DYNC2H1 gene with c.10606C>T(p.Arg3536*) inherited from the father and c.8954T>G(p.Val2985Gly) from the mother. Autosomal recessive inheritance was confirmed in both pedigrees. Mutations of c.5881A>G(p.Lys1961Glu) and c.8954T>G(p.Val2985Gly) in the DYNC2H1 gene were likely pathogenic variants and had not been reported before. The prenatal diagnosis did not identify the DYNC2H1 gene c.5881A>G(p.Lys1961Glu) mutation in the fetus (Ⅱ-7) in pedigree one, which was confirmed by the umbilical cord blood sample after birth. Conclusion:DYNC2H1 gene mutation underlies the fetal skeletal dysplasia in the two pedigrees.

Síndrome Towens-Brocks, presentación de caso / Towens-Brocks syndrome. Presentation of a case

RESUMEN Introducción: el Síndrome Townes-Brocks es una enfermedad genética malformativa, que se hereda de forma autosómica dominante, con penetrancia completa y expresividad muy variable. Caracterizada por una triada de defectos congénitos nivel de oído externo, anorrectales, y en la parte distal de las extremidades, sobre todo a nivel de los pulgares, causado por mutaciones en el gen SALL1, que codifica para el factor de transcripción, localizado en cromosoma 16q12.1. Presentación de caso: se presenta una lactante de nueve meses que al nacimiento se diagnosticó ano imperforado, apéndices preauriculares y primer dedo bífido. Se realizó de inmediato el diagnóstico clínico y la intervención quirúrgica que terminó en colostomía bien tolerada, se logró buena nutrición y desarrollo psicomotor. Conclusiones: se considera el diagnóstico clínico precoz, importante para efectuar intervenciones oportunas que permitan mejorar las funciones vitales de estos enfermos, así como brindar un adecuado asesoramiento genético a las familias.

ABSTRACT Introduction: Townes-Brocks syndrome is a malformation genetic disease, is an autosomal dominant genetic disorder, with complete penetrance and highly variable expressivity. It is characterized by a triad of congenital defects at the level of the external ear, anorectal and distal extremities, especially at the level of the thumbs, caused by mutations in the SALL1 gene, which codes for the transcription factor, located on chromosome 16q12.1. Case presentation: a 9-month-old female infant was diagnosed at birth with imperforate anus, preauricular appendix and bifid first finger. The clinical diagnosis was immediately made and the surgical intervention ended in a well-tolerated colostomy, achieving good nutrition and psychomotor development. Conclusions: early clinical diagnosis is considered important to carry out timely interventions to improve the vital functions on these patients, as well as to provide adequate genetic counseling to the families.

BARDET BIEDL SYNDROME IN PREGNANCY A CASE REPORT

Bardet Biedl Syndrome (BBS) is a rare idiopathic autosomal recessive disorder which affects multiple organs and organ systems. In India less than 15 cases have been reported so far. We present case of 41 year old third gravida who presented at 17 weeks of gestation. She had a suspicious history of delayed milestones in the previous child and ultrasound findings of echogenic kidneys, bilateral talipes, and polydactyly. Index child evaluation showed type-6 variant of BBS. Amniocentesis in the present pregnancy showed the same mutation in the fetus. The couple decided on termination of t pregnancy.

Monitoring of birth defects in perinatal infants born during 2015-2019 in Huainan City, Anhui Province / 中国基层医药

Objective:To analyze birth defects in perinatal infants in Huainan city, Anhui province.Methods:The data of perinatal infants with birth defects born during 2015-2019 who were monitored in nine national and provincial birth defect monitoring hospitals in Huainan City were collected. The changes in birth defects, the incidence of birth defects in infants ≥ 28 weeks, urban and rural area distribution of birth defects, type of defects, and the related factors of birth defects during a 5-year study period were analyzed.Results:A total of 90 466 perinatal infants with the incidence of birth defects of 89.87/10 000 were monitored during 2015-2019. The incidence of birth defects in Anhui Province was 139.74/10 000. The proportion of preterm infants < 28 weeks with birth defects among full-term births with birth defects was 30.93% and the proportion increased year by year during 2015-2019, with the proportion of 14.84%, 31.69%, 34.83%, 32.84% and 34.02% respectively. The top five birth defects detected during 2015-2019 were multiple fingers (toes) ( n = 189, 20.89/10 000), cleft lip ( n = 96, 10.61/10 000), external ear deformity ( n = 79, 8.73/10 000), congenital heart disease ( n = 65, 7.19/10 000) and syndactyly ( n = 40, 4.42/10 000). The incidence of birth defects in males and females was 102.77/10 000 and 85.28/10 000, respectively. The incidence of birth defects in urban and rural areas were 107.38/10 000 and 79.60/10 000, respectively. Conclusion:The incidence of birth defects in preterm infants < 28 weeks in Huainan City was lower than that in the whole Anhui Province. The incidence of birth defects in Huainan City differed in different years. The incidence of birth defects in males was higher than that in females. From 2016, the incidence of birth defects in urban area was higher than that in rural area. Birth defects mainly consisted of multiple fingers (toes), external ear deformity, congenital heart disease, cleft lip and syndactyly. The detection rate of birth defects in preterm (< 28 weeks) patients was increased year by year. Early intervention effectively decreased the incidence of birth defects and improved the quality of the population in Huainan City.

Síndrome de Ellis Van Creveld / Ellis Van Creveld syndrome

Resumen El síndrome de Ellis van Creveld es un trastorno autosómico recesivo, caracterizado por mutaciones en los genes ECV y ECV2, los cuales son importantes para el desarrollo osteocondral. A nivel mundial, se han reportado aproximadamente 300 casos ,presentándose con mayor frecuencia en poblaciones endogámicas. Se caracteriza por distrofias óseas, displasias ectodérmicas y malformaciones cardíacas. El diagnóstico clínico puede ser confirmado mediante pruebas moleculares. A continuación, se presenta el caso de una paciente diagnosticada con el síndrome, la cual fue evaluada de manera interdisciplinaria. Esta revisión permitió dar a conocer un nuevo caso de la patología, relacionar las manifestaciones clínicas de la paciente con la literatura y describir nuevos hallazgos que pueden correlacionarse con el síndrome.

Abstract Ellis Van Creveld syndrome is an autosomal recessive disorder, characterized by mutations of the genes ECV and ECV2, which are very important in the osteochondral development. Worldwide, there have been reported around 300 cases that are commonly evidenced in populations where endogamy is typical. It is clinically characterized by bone dystrophies, ectodermal dysplasias, and congenital heart defects; the diagnosis can be confirmed by molecular tests. In the lines below, a case of a patient that suffers from this syndrome, and that was examined in an interdisciplinary way will be presented. This review allows us to show a new case of this pathology, to relate the clinical symptoms of the patient with the existing literature, and to describe new findings that can be correlated with the Ellis Van Creveld condition.

Meckel-Gruber syndrome: a rare and lethal foetal anomaly

Meckel-Gruber syndrome (MGS) is a rare and lethal autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and bilateral dysplastic cystic kidneys. It can be associated with many other congenital malformations. The incidence of Meckel-Gruber syndrome ranges between 1 in 13,000 to 4,00,000 live births. Antenatal ultrasound examination establishes the diagnosis by identifying at least two of the major features. A case is presented that describes a baby with ambiguous genitalia, who presented with the triad of Meckel-Gruber syndrome. The baby died shortly after birth.

A rare case of polydactyly with multiple defects

Bardet-Biedl Syndrome (BBS) is a very rare genetically heterogenous disorder. Here is a case of 27 yr. old obese male presented with acute gastroenteritis with shock in our department. He had polydactyly in both upper limb and left lower limb, blindness since childhood, with difficult in learning and delayed onset of milestones. Patient抯 sibling (younger brother 20-year-old) also had same problems since childhood and one female baby died within few days of birth. He was having single testis. Patient was managed conservatively. The available literature on this syndrome was reviewed.

The lateral nail fold plasty in duplicated thumbs with a common nail / 中华整形外科杂志

Objective@#In this study, a new surgical technique was developed to reconstruct the lateral nail fold in the duplicated thumbs with a common nail and postoperative outcomes were evaluated.@*Methods@#From December 2012 to October 2015, sixteen duplicated thumbs with a common nail were treated in our hospital using a flap from resected finger pulp which did not include the nail and phalanx. Unilateral inverting suture was performed between the flap and nail bed to reconstruct the lateral nail fold and nail groove. Postoperative outcomes were evaluated by Wang-Gao scoring system (total 12).@*Results@#The follow-up period ranged from 10 to 45 months. The reconstructed nails were smooth and had a natural lunula, and the nail width was about 80%-100% of their normal sides. There was a right angle between the nail epithelium and lateral nail fold in four cases, and an acute angle in two cases. The reconstructed nails were asymmetrical in these thumbs. One patient showed a hypertrophy in the lateral nail fold. The reconstructed nails were evaluated by Wang-Gao scoring system: 10 in 2 cases, 11 in 4 and 12 in 10. All the cases had excellent results.@*Conclusions@#The nail width usually is more than 80% of the normal sides in the radial polydactyly with a common nail. The surgical technique can reconstruct a natural lateral nail fold and nail groove, and avoid the nail deformity caused by the Bilhaut-Cloquet procedure.

A rare case of Meckel Gruber syndrome

Meckel Gruber syndrome (MGS) is a rare lethal autosomal recessive disorder.  It is characterized by triad of features having occipital meningoencephalocele, polycystic kidneys and post-axial polydactyly. We report an antenatal patient detected with occipital meningoencephalocele in foetus on early anomaly scan at 15 weeks of gestation followed by foetal MRI which revealed the typical triad features strongly suggestive of MGS. The patient opted for medical termination of pregnancy and the abortus was autopsied, with the permission of the patient, for detailed evaluation of anomalies which were consistent with MGS. This case highlights the importance of a detailed foetal evaluation antenatally to detect anomalies which are incompatible with life and proper diagnosis as it has bearing on patient’s future obstetric outcome.

Síndrome de Ellis-van Creveld. Reporte de un caso en Ecuador / Ellis-van Creveld Syndrome. A case report in Ecuador / Síndrome de Ellis-Van Creveld. Relato de um caso no Equador

Resumen: El síndrome de Ellis-van Creveld es una rara anormalidad genética autosómica recesiva causada por mutaciones en el cromosoma 4p16. Presenta una tétrada típica: condrodistrofia, polidactilia postaxial, displasia ectodérmica y cardiopatía congénita, siendo esta última la principal determinante de la mortalidad. Desde que fue descrito en 1940, se han registrado 150 casos en la literatura científica; en Sudamérica son pocos los casos registrados y en Ecuador no se encontró ningún caso publicado. Se presenta un paciente asintomático de 20 años que acude a un control médico de rutina donde se evidencia un soplo cardíaco.

Summary: Ellis-van Creveld syndrome is a rare autosomal recessive disorder. It is caused by a mutation in 4p16 chromosome. It is characterized by a classical tetrad: chondrodystrophy, postaxial polydactyly, ectodermal dysplasia, and congenital heart defect. The congenital heart defect is the main determinant of mortality. Ellis-van Creveld syndrome was described in 1940; it has been registered 150 case reports. There are few reports in South America. In Ecuador, it wasn't found case reports. A 20 years old asymptomatic patient is presented, who goes to routine health care and is found to have a heart murmur.

Resumo: A síndrome de Ellis-van Creveld é uma esquisita doença autossômica recessiva. É causada por uma mutação no cromossomo 4p16. É caracterizada por quatro sinais típicas: condrodistrofia, polidactilia pós-axial, displasia ectodérmica e cardiopatia congênita. O defeito cardíaco congênito é o principal determinante da mortalidade. Desde que foi descrito em 1940 tenham sido registrados 150 relatos de caso. Na America do Sul existem poucos relatos, e no Equador não se encontrou nenhum publicado. É apresentado um paciente assintomático de 20 anos que vai para o controle médico de rotina, onde é encontrada uma bulha cardíaca.

A small supernumerary marker chromosome resulting in mosaic partial tetrasomy 4q26-q31.21 in a foetus with multiple congenital malformations

A parental diagnosis was performed for an unborn foetus of a healthy couple, who was due for ultrasound detection of multiple malformations and abnormal amniotic fluid karyotypes. For an accurate diagnosis, routine G-banding analysis and nextgeneration sequencing (NGS)were carried out. Finally, conventional cytogenetic analysis suggested that the foetus had a karyotype of47,XX,+mar[52]/46,XN,meanwhileNGSalso revealed a partial tetrasomy of 27.84Mbfrom4q26-q31.21 (117,385,735–145,225,759), and G-banding analysis excluded the couple to have carried the 4q26-q31.21 duplication. We have identified a de novo mosaic small supernumerary marker chromosomes (sSMC) derived from 4q26-q31.21 in a foetus with hemivertebra, polydactyly, abnormal ears, and heart and ventricular septal defect.

Variante patogénica homocigótica del gen BBS10 en un paciente con síndrome de Bardet-Biedl / A pathogenic homozygous variant of the BBS10 gene in a patient with Bardet Biedl syndrome

Resumen El síndrome de Bardet-Biedl es una enfermedad hereditaria, autosómica recesiva, con gran heterogeneidad de locus, que pertenece a las denominadas ciliopatías, denominadas así por la deficiencia funcional presente y porque las proteínas afectadas se localizan en el cilio primario. El síndrome afecta múltiples sistemas, con compromiso visual, renal, cognitivo, esquelético y gonadal, y obesidad. Este síndrome presenta una gran variabilidad intrafamiliar e interfamiliar. Se presenta el caso clínico de un paciente adolescente con diagnóstico de síndrome de Bardet-Biedl, así como su manejo, los resultados de la secuenciación de 22 genes y el análisis actualizado de la literatura médica. Se recopiló la información clínica y, previo consentimiento informado, se hizo la prueba de panel de secuenciación multigénica de los genes implicados. El paciente es hijo de la unión de personas consanguíneas. Fue el primer afectado en la familia y presentaba polidactilia posaxial, obesidad, micropene, retinitis pigmentaria y dificultades de aprendizaje. En el panel multigénico, se identificó la variante patogénica homocigótica c.39_46del en el gen BBS10 y otras variantes de genes BBS asociadas con la obesidad. Dado que el síndrome de Bardet-Biedl es una enfermedad huérfana rara, interpretar el pleiotropismo y la heterogeneidad de locus y de alelos, constituye un reto. La confirmación molecular permite el manejo adecuado de los pacientes, así como el seguimiento y el asesoramiento genético apropiados.

Abstract The Bardet-Biedl syndrome is an autosomal recessive hereditary disorder with vast locus heterogeneity that belongs to the so-called ciliopathies, whose proteins are localized in the primary cilia and present functional deficiency. The multisystemic features of the disease include ocular, renal, cognitive, skeletal, as well as gonadal involvement and obesity, among others, with high inter- and intrafamilial variability. We describe the clinical case of an adolescent male patient with Bardet-Biedl syndrome, including the approach, the results from a 22-gene sequencing panel, and the analysis of updated scientific literature. We collected the clinical data of the patient and, after obtaining the informed consent, we conducted a multigenic sequencing panel oriented to known implicated genes. The patient was born to consanguineous parents and was the first affected member of the family. He presented with postaxial polydactyly, obesity, micropenis, retinitis pigmentosa, and learning disability. The multigenic panel allowed the identification of the homozygous pathogenic variant c.39_46del in the BBS10 gene and in other BBS genes variants associated with obesity. As the Bardet-Biedl syndrome is a rare disease, it is challenging to interpret its pleiotropism and gene/allelic heterogeneity. Its confirmation by molecular tests allows an adequate approach, follow-up, and genetic counseling of the patient and the family.

Analysis of Congenital Postaxial Polydactyly of the Foot Using Magnetic Resonance Imagings / 대한정형외과학회잡지

PURPOSE: We aimed to evaluate the magnetic resonance imaging (MRI) findings of congenital postaxial polydactyly of the foot. MATERIALS AND METHODS: Three-hundred and forty-seven feet of 288 patients who underwent congenital postaxial polydactyly or polysyndactyly correction were divided into five subtypes according to the radiographic shapes of deformity origins (widened metatarsal head, bifid, fused duplicated, incompletely duplicated, or completely duplicated). MRIs were assessed to determine whether they unrevealed areas were fused or separated. MRI was also used to assess cases with radiographic phalangeal aplasia. RESULTS: Huge variations were noted in MRIs. Fusion or separation at the base or head between original and extra digits were observed, and MRI effectively depicted phalangeal aplastic areas. CONCLUSION: MRI evaluations of congenital postaxial polydactyly of the foot are useful for determining the anatomical statuses which were not visualized by plain radiography (level of evidence: 3).

Application of dorsal double-wing flap for reconstruction of the web space in the fifth and fourth toe polysyndactyly / 中华整形外科杂志

Objective@#To explore the application of dorsal double-wing flap for reconstruction of the web space in the fifth and fourth toe polysyndactyly.@*Methods@#99 patients (112 feet) with polysyndactyly of the fifth toe fused with the fourth toe were treated, 75 of which were incomplete and 37 were complete fusion of the fourth and fifth toes. The fifth toes showed various degrees of fibular deviation and minor deformities. Excision of polydactyly and then with the use of wedge osteotomy correction deviation. Using 77 traditional and 35 modified dorsal double-wing flap for reconstruction of the web space, and close the lateral sides of toes with flaps from polydactyly. The distal soft tissue of polydactylies were used lengthening the reconstructed fifth toes.@*Results@#Polydactyly excision and syndactyly releasing in same procedure and lateral sides of the toes were all closed with flaps without skin grafts. Patients were followed up average 27 months after operation, the constructed web space showed good appearance, with slightly deeper or normal location. The fibular deviation were complete correction, and minor deformities were improved.@*Conclusions@#The dorsal double-wing flap is used for reconstruction of the web space in the fifth and fourth toes polysyndactyly without skin grafts. Reconstruction of the web depth, combined with lengthen distal end of the fifth could improve the toe appearance. Compared with traditional dorsal double-wing flap reconstruction of the web space, the modified flaps have better appearance in palmar of foot.

Short rib-thoracic dysplasia syndrome (type Ⅲ) caused by compound heterozygous mutation in DYNC2H1: a case report / 中华围产医学杂志

We reported one fetus who was identified with significantly short humeri and femora,bulging abdomen and narrowed chest at 22+2 weeks' gestation,which was consistent with clinical findings at birth.Genetic analysis revealed that this was a case of short-rib thoracic dysplasia syndrome (type Ⅲ) caused by compound heterozygous mutation in DYNC2H1.We summarized the features of prenatal ultrasound imaging and results of postpartum genetic analysis of this case to provide information for prenatal ultrasound diagnosis and postpartum consultation.

Novel mutations in the BBS12 gene of two Chinese Bardet-Biedl syndrome pedigrees / 中华肾脏病杂志

Objective To Summarize and review the clinical data of two Bardet-Biedl syndrome (BBS) children so as to improve our understanding of the disease.Methods Clinical data of two BBS pedigree were collected.Gene analysis was performed by exon capture and next-generation sequencing,validated using Sanger sequencing.Results Both cases were male,Han nationality,born with polydactyly and had rapid weight gain after birth.They went to see the pediatric endocrinologist due to obesity,and found increased serum creatinine level,so were referral to pediatric nephrologists.Case one was further diagnosed rod-cone dystrophy,bilateral renal multiple cysts (chronic kidney disease,stage 4),atrial septal defect,mental retardation,hypertension and abnormal hearing.Two novel heterozygous compound mutation of BBS12 gene [c.1604T ＞ G (p.V535G) paternal,c.173delA (p.E58Efs*5) maternal] and one known BBS4 missense mutation (paternal) were detected.Case two was detected multiple cysts in kidneys by ultrasound in fetal phase.He was suspected to have autism.He had small penis,hypertension and renal injury (chronic kidney disease,stage 3).Two novel heterozygous compound mutation of BBS12 gene [c.1783T ＞ C (p.W595R) paternal,c.1749_1750delA (p.R584Dfs*54) maternal] were detected.All mutations were predicted to be harmful.Conclusions BBS is a rare disease.It is difficult to be diagnosed at early age.Polydactyly and obesity can be the early two symptoms for seeing doctors.Few cases have been diagnosed upon gene analysis.In this study,the mutation of BBS12 in Chinese and 4 novel mutations in BBS12 with severe renal injury are reported for the first time.It will extend the spectrum of BBS gene mutations.

Active and passive maternal smoking during pregnancy and risk of having a child with polydactyly: a case-control study / 中华流行病学杂志

Objective The number of children with polydactyly is increasing.In addition to genetic factors,an influence of maternal behavior or environmental effects during pregnancy is becoming increasingly apparent.However,epidemiological data on these effects are lacking.Methods This hospital-based,case-control study enrolled 143 infants with polydactyly and 286 controls without genetic diseases to evaluate the association between active and passive maternal smoking during pregnancy and the likelihood of giving birth to a child with polydactyly.Results Active and passive maternal smoking during pregnancy was associated with an increased risk of giving birth to a child with polydactyly (active smoking:OR=4.74,95％CI:1.43-15.65,P=0.011;passive smoking:OR=2.42,95％CI:1.32-4.44,P=0.004).After adjusting for confounders,smoking during pregnancy remained significant influence on polydactyly (active smoking:aOR=7.27,95％ CI:1.72-30.72,P=0.007;passive smoking:aOR=2.41,95％ CI:1.11-5.23,P=0.026).Conclusion Active and passive maternal smoking during pregnancy appears to be a risk factor for polydactyly in newborns.