Narrow Thorax Research Articles

Lethal short limb dwarfism: thanatophoric dysplasia- type I.

A 30-year-old, mother, delivered a 2.6 kg term female child by caesarean section, in view of brow presentation and failure of induction of labor. Antenatal ultrasound of mother at 5th and 7th month had detected a fetus with short curved limbs and small chest, with a suspicion of achondroplasia. At birth, the neonate was noted to have dysmorphic features, macrocephaly, midfacial hypoplasia, depressed nasal bridge, low set ears, short limbs, short narrow thorax with lumbar lordosis [Table/Fig-1,​,2]2] . Radiological survey of the child clinched the diagnosis of Thanatophoric Dysplasia (TD) Type I [Table/Fig-3]. Echocardiography screening revealed atrial septal defect, ventricular septal defect and patent ductus arteriosus with severe pulmonary hypertension. [Table/Fig-1]: Reveals frontal bossing, depressed nasal bridge, prominent eyes, short neck, short and narrow thorax, short limbs [Table/Fig-2]: Lateral view of the neonate shows large head, short neck, prominent forehead, low set ears and lumbar lordosis [Table/Fig-3]: Ray- Skeletal Survey : Skeletal Survey shows short bowed long bones with bullous end, short ribs, narrow thorax, handle bar appearance of clavicle, vertebral bodies short end superiorly & inferiorly, dysplastic acetabuli with flat acetabular roof, ... Skeletal dysplasias constitute a heterogeneous group of bone growth disorders resulting in abnormal shape and size of the skeleton. TD is the most common lethal osteochondrodysplasias with a prevalence of 1:20,000 to 1:40,000 births [1]. It is characterized by marked underdeveloped skeleton and short-limb dwarfism. The term ‘thanatophoric’ derived from the Greek word “thanatophorus”, means “death bringing” and was first described by Maroteux [1,3]. TD is caused by activation of FGFR3 gene located on the short arm of chromosome 4 leading to negative regulation of bone growth [1,2]. The activation of FGFR3 in a majority is due to denovo mutations. There are two clinical types of TD which closely resemble in their clinical features; however have distinct radiological features and genetic mutations [3]. In Type I TD, the amino acid arginine, at 248 position, is substituted by cystine and in Type II TD the lysine at 650 position is replaced by Glutamate in most cases[1]. Type 1, the more commonly encountered form is characterized by a normal-shaped skull and curved (telephone receiver shaped) long bones, especially seen in femur bone, whereas type II is associated with a cloverleaf-shaped skull and straight femurs [1-3]. The phenotypic features of TD range from severe shortening of limbs, macrocephaly, frontal bossing, wide fontanel’s, cloverleaf skull, prominent eyes, to long narrow bell shaped thorax resulting in pulmonary hypoplasia [3]. Radiological features are short, cupped and anteriorly splayed ribs with severe hypoplasia of pelvic bones, 4short and flared femur with medial spike (telephone receiver shaped in Type I), large calvarium with short base and small foramen magnum, cloverleaf skull and thin flat vertebrae. The pelvis characteristically shows decreased vertical height and increased horizontal width of iliac bones with flat acetabulae [2]. The diagnostic sonographic criteria are severe rhizomelic-micromelia with bowing of long bones [3]. The metaphyseal ends can have a thorn like projection secondary to prominent ossification resulting in ‘Maple leaf like’ contour of metaphysis of tubular bones. The close differential diagnoses of TD, includes osteogenesis imperfecta type II and III, which is characterized by fracture of long bones and achondrogenesis characterized by extreme hypomineralization. Other rarer differentials include achondroplasia, perinatal hypophosphatemia, campomelic dysplasia and hypochondrogenesis [3]. Prognosis for TD is grim, with stillbirths or deaths occurring during early neonatal period because of respiratory failure due to lung hypoplasia or brain stem compression due to underlying hydrocephalus [3]. Postnatal treatment involves life-support measures, parental counselling and provision-of-comfort care for the newborn [2]. Prenatal diagnosis and genetic counselling can be done with the help of antenatal ultrasonography and/or molecular studies, especially for fetuses with short limbs. Early and timely detection of lethal forms on antenatal scans will help in obstetricians and parents to take decision regarding option of medical termination of pregnancy [1,3].

Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: Prenatal diagnosis and literature review

ObjectiveWe describe a prenatal molecular diagnosis of hypochondroplasia (HCH) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH. Case reportA 28-year-old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus. The woman had a body height of 152 cm. Her husband had a body height of 180 cm. Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs. Fetal biometry measurements were as follows: biparietal diameter = 7.38 cm (30 weeks); head circumference = 28.14 cm (30 weeks); abdominal circumference (AC) = 24.64 cm (30 weeks); femur length (FL) = 3.97 cm (<5th centile); FL/AC ratio = 0.161 (normal > 0.18); humerus = 3.64 cm (<5th centile); radius = 3.49 cm (30 weeks); ulna = 3.76 cm (<5th centile); tibia = 3.67 cm (<5th centile); and fibula = 3.72 cm (<5th centile). The digits and craniofacial appearance were normal. A tentative diagnosis of achondroplasia (ACH) was made. DNA testing for the FGFR3 gene and whole-genome array comparative genomic hybridization (aCGH) analysis were performed using cord blood DNA obtained by cordocentesis. FGFR3 mutation analysis revealed a de novo heterozygous c.833A > G, TAC > TGC transversion in exon 7 leading to a p.Tyr278Cys (Y278C) mutation in the FGFR3 protein. aCGH analysis revealed no genomic imbalance in cord blood. After delivery, the fetus had short limbs, a narrow thorax, brachydactyly, and relative macrocephaly. Cytogenetic analysis of cultured placental cells revealed a karyotype of 46,XX. ConclusionPrenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR3.

WDR34 Mutations that Cause Short-Rib Polydactyly Syndrome Type III/Severe Asphyxiating Thoracic Dysplasia Reveal a Role for the NF-κB Pathway in Cilia

Short-rib polydactyly (SRP) syndrome type III, or Verma-Naumoff syndrome, is an autosomal-recessive chondrodysplasia characterized by short ribs, a narrow thorax, short long bones, an abnormal acetabulum, and numerous extraskeletal malformations and is lethal in the perinatal period. Presently, mutations in two genes, IFT80 and DYNC2H1, have been identified as being responsible for SRP type III. Via homozygosity mapping in three affected siblings, a locus for the disease was identified on chromosome 9q34.11, and homozygosity for three missense mutations in WDR34 were found in three independent families, as well as compound heterozygosity for mutations in one family. WDR34 encodes a member of the WD repeat protein family with five WD40 domains, which acts as a TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway. We showed, through structural modeling, that two of the three mutations altered specific structural domains of WDR34. We found that primary cilia in WDR34 mutant fibroblasts were significantly shorter than normal and had a bulbous tip. This report expands on the pathogenesis of SRP type III and demonstrates that a regulator of the NF-κB activation pathway is involved in the pathogenesis of the skeletal ciliopathies.

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

Sensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare multiple anomaly syndrome with distinctive craniofacial appearance, skeletal, ectodermal, connective tissue, renal, and liver anomalies. Dramatic advances with next-generation sequencing have expanded its phenotypic variability and molecular heterogeneity. We review 39 patients including two new patients, one with compound heterozygous novel mutations in WDR35 and a previously unreported multisutural craniosynostosis that may be a part of Sensenbrenner syndrome. In 14 of 25 (56.0%) patients pathogenic mutations have been identified in 4 different genes that regulate (intraflagellar) cilia transport. We compared Sensenbrenner syndrome to asphyxiating thoracic dystrophy-Jeune syndrome (ATD-JS) and other ciliopathies. Our analyses showed that the high anterior hairline, forehead bossing and dolichocephaly (accompanied by sagittal craniosynostosis in more than half of the patients) occur in almost all patients with Sensenbrenner syndrome. Metaphyseal dysplasia with narrow thorax, proximal limb shortness, and short fingers are typical of Sensenbrenner syndrome and ATD-JS. Respiratory complications have been reported in both syndromes, usually less severe with Sensenbrenner syndrome. Proposed diagnostic criteria for Sensenbrenner syndrome include the distinctive craniofacial appearance, ubiquitous brachydactyly and ectodermal anomalies, and sagittal craniosynostosis. Mild heart defects have been noted, but there have been no atrioventricular canal or heterotaxy defects that are common in Ellis-Van Creveld syndrome. We anticipate that the steady identification of molecularly defined patients may allow correlation of phenotype and genotype. Additional natural history data will improve genetic counseling and current guidelines.

Molecular Analysis of a Case of Thanatophoric Dysplasia Reveals Two de Novo FGFR3 Missense Mutations located in Cis

Thanatophoric dysplasia (TD) is the most common form of lethal skeletal dysplasia. It is primarily an autosomal dominant disorder and is characterised by macrocephaly, a narrow thorax, short ribs, brachydactyly, and hypotonia. In addition to these core phenotypic features, TD type I involves micromelia with bowed femurs, while TD type II is characterised by micromelia with straight femurs and a moderate to severe clover-leaf deformity of the skull. Mutations in the FGFR3 gene are responsible for all cases of TD reported to date. The objective of the study here was to delineate further the mutational spectrum responsible for TD. Conventional polymerase chain reaction (PCR), allele-specific PCR, and sequence analysis were used to identify FGFR3 gene mutations in a fetus with a lethal skeletal dysplasia consistent with TD, which was detected during a routine antenatal ultrasound examination. In this report we describe the identification of two de novo missense mutations in cis in the FGFR3 gene (p.Asn540Lys and p.Val555Met) in a fetus displaying phenotypic features consistent with TD. This is the second description of a case of TD occurring as a result of double missense FGFR3 gene mutations, suggesting that the spectrum of mutations involved in the pathogenesis of TD may be broader than previously recognised.

Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families

BackgroundAsphyxiating Thoracic Dysplasia (ATD) belongs to the short rib polydactyly group and is characterized by a narrow thorax, short long bones and trident acetabular roof. Other reported features include polydactyly,...

Orthodontic and surgical management of cleidocranial dysplasia

Cleidocranial dysplasia (CCD), an autosomal dominant disorder with a prevalence of 1 in 1,000,000 individuals, is mainly caused by mutations in Runx2, a gene required for osteoblastic differentiation. It is generally characterized by hypoplastic clavicles, narrow thorax, and delayed or absent fontanel closure. Importantly, its orofacial manifestations, including midfacial hypoplasia, retained primary teeth, and impacted permanent and supernumerary teeth, severely impede the well-being of affected individuals. Successful treatment of the orofacial problems requires the combined efforts of dental specialists. However, only a few successfully treated cases have been reported because of the rarity of CCD and complexity of the treatment. This article presents the University of California, San Francisco (UCSF) treatment protocol for the dentofacial manifestations of CCD based on two treated and 17 diagnosed cases. The records of two patients with CCD who had been treated at the UCSF School of Dentistry and the treatment options reported in the literature were reviewed. The UCSF treatment protocol produced a successful case and a partially successful one (inadequate oral hygiene in the retention stage resulted in decay and loss of teeth). It provides general guidelines for successfully treating the orofacial manifestations of CCD.

Jeune Syndrome: Considerations for Management of Asphyxiating Thoracic Dystrophy

Jeune syndrome (JS), or asphyxiating thoracic dystrophy, is a rare genetic disorder characterized by a small, narrow thorax, with associated shortening of limbs. Children with JS present with variable degrees of respiratory distress, frequently lethal in the neonatal period. Other associated complications include renal, hepatic, gastrointestinal, and retinal dysfunction. Management focuses on stabilization and support of respiratory function. Treatment may be palliative in nature or corrective. In recent years, the advance in surgical treatment of the thoracic hypoplasia in JS offers hope to those families with a child suffering from the syndrome. Even with increased research into treatment of this disorder, prognosis is usually poor. Comorbidities associated with JS lead to serious organ dysfunction in later years. Families who have a child with JS need genetic counseling and education focusing on the seriousness of the disorder, the risks and benefits of treatment, and the lifelong needs of those with JS.

First-trimester prenatal diagnosis of Ellis–van Creveld syndrome

ObjectiveTo present the perinatal findings and first-trimester molecular and transabdominal ultrasound diagnosis of a fetus with Ellis–van Creveld (EvC) syndrome. Case ReportA 35-year-old woman was referred for genetic counseling at 13 weeks of gestation because of a family history of skeletal dysplasia. She had experienced one spontaneous abortion, and delivered one male fetus and one female fetus with EvC syndrome. During this pregnancy, a prenatal transabdominal ultrasound at 13+4 weeks of gestation revealed a nuchal translucency (NT) thickness of 2.0 mm, an endocardial cushion defect, postaxial polydactyly of bilateral hands, and mesomelic dysplasia of the long bones. Amniocentesis was performed at 13+5 weeks of gestation. Results of a cytogenetic analysis revealed a karyotype of 46,XX and that of a molecular analysis revealed compound heterozygous mutations of c.1195C>T and c.871-2_894del26 in the EVC2 gene. Prenatal ultrasound at 16 weeks of gestation showed a fetus with short limbs, an endocardial cushion defect, and postaxial polydactyly of bilateral hands. The parents decided to terminate the pregnancy, and a 116-g female fetus was delivered with a narrow thorax, shortening limbs, and postaxial polydactyly of the hands. ConclusionPrenatal diagnosis of an endocardial cushion defect with postaxial polydactyly should include a differential diagnosis of EvC syndrome in addition to short rib–polydactyly syndrome, Bardet–Biedl syndrome, orofaciodigital syndrome, Smith–Lemli–Opitz syndrome, and hydrolethalus syndrome.

Asphyxiating Thoracic Dysplasia: clinical and molecular review of 42 families

Asphyxiating Thoracic Dysplasia (ATD) ((MIM 208500, MIM 6112633, MIM 613091, MIM 61819, MIM614376) belongs to the short rib polydactyly group and is characterized by a long and narrow thorax, short long bones and trident acetabular roof. Polydactyly, retinal degeneration, cystic renal and liver diseases have been occasionally reported. Today, mutations in IFT80 (MIM 611177), DYNC2H1 (MIM 603297), TCC21B (MIM 612014) and WDR19 (MIM 608151) genes have been reported in ATD. Through a national grant (PHRC, AOM 06031), we have collected 55 ATD cases including 29 fetuses issued from 42 families who benefit the combined approach of deep phenotyping and molecular screening of IFT80 and DYNC2H1. The series included 26 alive cases ranging in age from 6 months to 36 years. Respiratory treatment was needed in 46%, including positive pression respiration, and invasive or non-invasive ventilation. Cystic renal and liver diseases occur in 16% of cases; whereas retinal degeneration was present in 40 % cases aged more than 2 years (6/15). The molecular screening allowed us to detect DYNC2H1 mutations in 63% and IFT80 mutations in 6%. In 6 cases, only one heterozygote mutation in either IFT80 or DYNC2H1 was identified. Finally, the two genes were excluded in 31% cases. These preliminary results emphasize that DYNC2H1 is the major gene responsible for ATD. The presence of only one mutation (27% of mutated cases) may suggest a digenic diallelic inheritance. Ongoing studies will hopefully lead to the identification of other disease genes.

Exome sequencing for disease gene discovery in Jeune’s Asphyxiating Thoracic Dystrophy

Asphyxiating Thoracic Dystrophy (ATD) is a clinically heterogeneous, autosomal recessive skeletal dysplasia characterized primarily by an abnormally narrow thorax with short ribs and short limbs. It has an estimated incidence of ~1 out of every 130,000 live births. Most patients die in early infancy or early childhood from respiratory insufficiency due to a small thorax. To date, four genes and one additional loci have been found to cause ATD in an autosomal recessive fashion. All four known genes are essential for normal primary cilia function. We employed the use of exome sequencing of seven unrelated patients affected with ATD to identify candidate mutations responsible for or contributing to the disorder. To maximize the success of gene discovery, we used Agilent’s SureSelect Exome Pull Down capturing 50 Mb of the protein-coding exome. Each sample library was sequenced using a single lane of Illumina HiSeq. We generated 252Gb of paired-end sequence data with a mean coverage of 115X per sample. The sequencing data was aligned using Novoalign and variants were called using the Genome Analysis Toolkit. Variants were filtered against dbSNP135, 69 complete Genomics samples, 95 NIEHS EGP exome samples, 5400 exomes from the NHLBI Exome Sequencing Project, and 40 in-house exome samples. Only mutations that were present in the above controls in the homozygous state were removed from the candidate list. After filtering, potential disease-causing mutations representing two known genes and four novel genes were found in all seven individuals.

703 Case Report - A Patient with Bone Formation Defects During Prenatal Life Diagnosed as ‘Shwachman-Diamond Syndrome’

CaseReportShwachman-Diamond syndrome(SDS) is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, hematological dysfunction and skeletal abnormalities during development after birth and varies with age. The patient...

WDR35 mutation in siblings with Sensenbrenner syndrome: A ciliopathy with variable phenotype

Sensenbrenner syndrome and unclassified short rib-polydactyly conditions are ciliopathies with overlapping phenotypes and genetic heterogeneity. Mutations in WDR35 were identified recently in a sub-group of patients with Sensenbrenner syndrome and in a single family that presented with an unclassified form of short-rib polydactyly (SRP) syndrome. We report on siblings with an unusual combination of phenotypes: narrow thorax, short stature, minor anomalies, developmental delay, and severe hepatic fibrosis leading to liver failure and early death in two of the children. Both parents were unaffected suggesting autosomal recessive inheritance. The family and their affected children were followed over a decade. Exome sequencing was performed in one affected individual. It showed a homozygous missense mutation in a highly conserved position of the WDR35 gene. This family represents a WDR35-ciliopathy with a complex clinical presentation that includes significant overlap of the phenotypes described in Sensenbrenner syndrome and the unclassified SRPs. The accurate molecular diagnosis of this family exemplifies the power of exome sequencing in the diagnosis of Mendelian disorders and enabled us to broaden and refine our understanding of Sensenbrenner syndrome and SRP. Detailed genotype-phenotype information is provided as well as discussion of previously reported cases.

Polydactyly and ostium primum type atrial septal defect: Ellis-van Creveld syndrome

Comorbid polydactyly and atrial septal defect (ASD) is a very rarely seen anomaly. Basic clinical findings of Ellis-van Creveld syndrome include muscular skeletal disorders in the hands in 100% of cases, additional symmetrical postaxial polydactyly in the feet in 10-25% of cases, disproportionate dwarfism, a narrow thorax leading to respiratory problems, ectodermic dysplasia in the skin, nails, and teeth, a high palate, malocclusion, micrognathia, and congenital heart diseases, especially ASDs, in almost half of the patients (50-60%). In this article, we report a case with polydactyly and primum type ASD along with the surgical treatment and outcomes.

Late survival in Ellis–van Creveld syndrome – A case report

Ellis–van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac anomalies. Acromelic shortening of upper and lower limbs, genu valgum, multiple frenula, deformed teeth, short ribs and narrow thorax and congenital heart diseases complete the picture. The patients with the syndrome rarely survive into adulthood. Here, we report a lady with EVC presenting for the first time in middle age.

Prenatal diagnosis and molecular genetic analysis of short rib-polydactyly syndrome type III (Verma-Naumoff) in a second-trimester fetus with a homozygous splice site mutation in intron 4 in the NEK1 gene

ObjectiveTo demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type III short rib-polydactyly syndrome (SRPS) (Verma-Naumoff). Case ReportA 34-year-old woman with no past history of fetal SRPS was referred to the hospital at 21 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed a narrow thorax, short ribs, short limbs with marginal spurs, and postaxial hexadactyly in both the hands and feet. A diagnosis of SRPS III (Verma-Naumoff) was made. Amniocentesis was performed. The karyotype was 46,XY. Molecular genetic analysis of the amniotic fluid cells identified a homozygous splice site mutation in intron 4 (c.331-1 A > G) or IVS4-1 A > G in the NEK1 gene. The parents were heterozygous for the mutation. The pregnancy was subsequently terminated and a malformed fetus was delivered with prominent forehead, a flattened nasal bridge, a narrow and short trunk, a protuberant abdomen, bilateral postaxial polydactyly and syndactyly of the hands and feet, and micromelic limbs. No facial cleft or genital abnormality was noted. The radiograph was consistent with SRPS III. ConclusionPolydactyly, micromelia, metaphyseal spurs, widened humeral metaphyses, and shortened ribs can be prominent prenatal ultrasound findings of SRPS III. The present case provides evidence for a correlation of a mutation in the NEK1 gene with SRPS III.

Shwachman-Diamond syndrome: a complex case demonstrating the potential for misdiagnosis as asphyxiating thoracic dystrophy (Jeune syndrome)

BackgroundThe differential diagnosis of a neonate or fetus presenting with a bell-shaped or long narrow thorax includes a wide range of bony dysplasia syndromes. Where this is accompanied by respiratory distress, asphyxiating thoracic dystrophy (ATD, Jeune syndrome) is an important potential diagnosis. Shwachman-Diamond syndrome (SDS) is widely recognised as a cause of exocrine pancreatic dysfunction, short stature and bone marrow failure. It is not so well appreciated that rib and/or thoracic cage abnormalities occur in 30–50% of patients and that, in severe cases, these abnormalities may lead to thoracic dystrophy and respiratory failure in the newborn. There are, however, at least three previous case reports of children who were initially diagnosed with ATD who were subsequently shown to have SDS.Case presentationThis report details the case history of a patient misdiagnosed as having ATD as a neonate following the neonatal asphyxial death of her brother. She subsequently developed progressive pancytopenia but was only diagnosed with SDS at 11 years of age after referral for haematopoietic stem cell transplantation for bone marrow failure accompanied by trilineage dysplasia and clonal cytogenetic abnormalities on bone marrow examination. Subsequent testing revealed the presence of fat globules in stools, reduced faecal chymotrypsin, fat-soluble vitamin deficiency, metaphyseal dysplasia on skeletal survey and heterozygous mutations of the SBDS gene.ConclusionThis report highlights the potential for diagnostic confusion between ATD and SDS. It is important to include SDS in the differential diagnosis of newborns with thoracic dystrophy and to seek expert clinical and radiological assessment of such children.

Thanatophoric Dysplasia in Newborn Twins: Case Report and Literature Review

Thanatophoric dysplasia (TD) is an osteochondrodysplasia always lethal in the neonatal period. The vast majority of cases are due to de novo mutations. It is divided into two types: a short curved femur characterizes type 1, while a straighter femur with clover leaf skull characterizes type 2. In thanatophoric dysplasia the limbs are very short. The rib cage is small. The vertebral bodies of the spine are greatly reduced in height with wide spaces between them. Autosomal dominant mutations in the fibroblast growth factor receptor 3 gene (FGFR3), which has been mapped to chromosome band 4p16.3, results in both subtypes. This condition has characteristic sonographic features that suggest the diagnosis prenatally. Thanatophoric fetuses usually die within the first 48 hours of life from pulmonary hypoplasia caused by a narrow thorax, leading to respiratory insufficiency . We reported twin dizygote cases of type 1 TD with similar findings adjusting with TD for the first time, along with a short review of the available literature.

Morphometrics and Morphology of Rice blue beetleLeptispa pygmaea(Baly.): (Coleoptera:Chrysomelidae)

The minor pest, blue beetle, Leptispa pygmaea (Baly.), is attaining status of a major pest by causing much damage to different crops in India. Attempts were made to study morphometrics and morphology of the beetle for correct identification and management. The beetle was found to lay oval eggs; measuring 0.20 mm length and 0.12 mm width hatching into creamy white grubs with two spiny projections on head and two tubular projections on posterior end of the body. The head capsule of all five instars measured 0.17, 0.20, 0.23, 0.26 and 0.26 mm wide, respectively. It pupated on leaves while attached loosely by its posterior end. The brown pupa measured 3.89 mm (length);1.32 mm (width). The adult beetle was metallic greenish yellow with longer antennae, narrow thorax and a long body. The female beetle could be differentiated by its shorter antennae, broader thorax and stouter body. The antennal scape was broader in the female compared to that of the male. The male and female reproductive system included aedeagus (length of 1.36 mm; width of 0.07 mm (anterior) and 0.10 mm (posterior)), two parts of tegmen, siphon and spermatheca with two lateral coxites (1.60 mm long; 0.52 mm wide), respectively.

Two novel heterozygous mutations of EVC2 cause a mild phenotype of Ellis–van Creveld syndrome in a Chinese family

Ellis-van Creveld syndrome (EvC, chondroectodermal dysplasia; OMIM 225500) is an autosomal recessive skeletal dysplasia with associated multisystem involvement. The syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, and abnormal teeth. Congenital heart defects occur in 50-60% of cases. In this study, we report EvC in a 6-year-old Chinese girl with hypodontia and polydactyly, mild short stature, and abnormalities of the knee joints. No signs of short ribs, narrow thorax, or congenital heart defects were found in this patient. The EvC phenotype shares some similarity with Weyers acrofacial dysostosis (Weyer; OMIM 193530), an autosomal dominant disorder clinically characterized by mild short stature, postaxial polydactyly, nail dystrophy, and dysplastic teeth. Mutations in EVC or EVC2 are associated with both EvC syndrome and Weyers acrodental dysostosis, but the two conditions differ in the severity of the phenotype and their pattern of inheritance. In this study, two novel heterozygous EVC2 mutations, IVS5-2A > G and c.2653C > T (Arg885X), were identified in the patient. The IVS5-2A > G mutation was inherited from the patient's mother and the c.2653C > T from her father. Her parents have no phenotypic symptoms similar to those of the patient. These findings extend the mutation spectrum of this malformation syndrome and provide the possibility of prenatal diagnosis for future offspring in this family.