Cleidocranial dysplasia presenting with retained deciduous teeth in a 15-year-old girl: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cleidocranial dysplasia is a rare congenital defect of autosomal dominant inheritance caused by mutations in the <it>Cbfa1 </it>gene, also called <it>Runx2</it>, located on the short arm of chromosome 6. It primarily affects bones which undergo intramembranous ossification. This condition is of clinical significance to dentistry due to the involvement of the facial bones, altered eruption patterns and multiple supernumerary teeth.</p> <p>Case presentation</p> <p>Our patient, a 15-year-old Indian girl, presented with the typical features of prolonged retention of deciduous dentition and delayed eruption of permanent teeth, that is, mandibular prognathism along with other skeletal abnormalities like shrugged shoulder and the absence of clavicles. A multidisciplinary approach was followed, comprising orthodontic, surgical and pedodontic teams for management.</p> <p>Conclusion</p> <p>Successful treatment of such a case lies in a holistic approach that takes care of all aspects, including the primary pathology, the deformity itself and even the psychological angle.</p

RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant human skeletal disorder comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth, short stature, and other skeletal abnormalities. It is known that mutations in the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index cases with typical CCD. One of the patients was a familial case and the others were sporadic cases. Sequencing identified four mutations. Three were caused by single nucleotide substitutions, which created a nonsense (p.R391X), two were missense mutations (p.R190W, p.R225Q), and the forth was a novel mutation (c.1119delC), a one-base deletion. Real time quantitative PCR adapted to determine copy numbers of the promoter, all exons and the 3’UTR region of the RUNX2 gene detected the deletion of a single allele in a sporadic case. The results extend the spectrum of RUNX2 mutations in CCD patients and indicate that complete deletions of the RUNX2 gene should be considered in those CCD patients lacking a point mutation detected by direct sequencing

Jeune syndrome: description of 13 cases and a proposal for follow-up protocol

Jeune syndrome (asphyxiating thoracic dystrophy, ATD) is a rare autosomal recessive skeletal dysplasia characterized by a small, narrow chest and variable limb shortness with a considerable neonatal mortality as a result of respiratory distress. Renal, hepatic, pancreatic and ocular complications may occur later in life. We describe 13 cases with ages ranging from 9 months to 22 years. Most patients experienced respiratory problems in the first years of their life, three died, one experienced renal complications, and one had hepatic problems. With age, the thoracic malformation tends to become less pronounced and the respiratory problems decrease. The prognosis of ATD seems better than described in literature and in our opinion this justifies long term intensive treatment in the first years. We also propose a follow-up protocol for patients with ATD

Ciliopathies: an expanding disease spectrum

Ciliopathies comprise a group of disorders associated with genetic mutations encoding defective proteins, which result in either abnormal formation or function of cilia. As cilia are a component of almost all vertebrate cells, cilia dysfunction can manifest as a constellation of features that include characteristically, retinal degeneration, renal disease and cerebral anomalies. Additional manifestations include congenital fibrocystic diseases of the liver, diabetes, obesity and skeletal dysplasias. Ciliopathic features have been associated with mutations in over 40 genes to date. However, with over 1,000 polypeptides currently identified within the ciliary proteome, several other disorders associated with this constellation of clinical features will likely be ascribed to mutations in other ciliary genes. The mechanisms underlying many of the disease phenotypes associated with ciliary dysfunction have yet to be fully elucidated. Several elegant studies have crucially demonstrated the dynamic ciliary localisation of components of the Hedgehog and Wnt signalling pathways during signal transduction. Given the critical role of the cilium in transducing “outside-in” signals, it is not surprising therefore, that the disease phenotypes consequent to ciliary dysfunction are a manifestation of aberrant signal transduction. Further investigation is now needed to explore the developmental and physiological roles of aberrant signal transduction in the manifestation of ciliopathy phenotypes. Utilisation of conditional and inducible murine models to delete or overexpress individual ciliary genes in a spatiotemporal and organ/cell-specific manner should help clarify some of the functional roles of ciliary proteins in the manifestation of phenotypic features

Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis

We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia, Autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses, Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type TV with onset in the early second trimester, (C) 1999 Wiley-Liss, Inc.</p

Asymptomatic maternal myasthenia as a cause of the Pena-Shokeir phenotype.

We report six sibs with arthrogryposis multiplex congenita and a Pena-Shokeir phenotype, born to a healthy woman who was discovered to have asymptomatic myasthenia gravis (MG). This is the first report of anti-acetylcholine receptor (AChR) antibodies causing fetal akinesia/hypokinesia sequence in the offspring of an asymptomatic mother