Apert syndrome: A dermatologist’s perspective

Apert syndrome is a Type 1 acrocephalosyndactyly syndrome presenting predominantly with craniofacial malformations and syndactyly. It can present with a multitude of clinical features involving any system of the body. A literature search of the PubMed electronic database was performed using the keywords “Apert syndrome” and “dermatology” in the title. The relevant references of the included articles were traced and included. A total of 27 articles appeared, the abstracts of which were screened and reviewed by both the authors independently for inclusion. After carefully analyzing all papers case by case, 21 such cases were retrieved. Cases presenting with other clinical features apart from dermatological features were also reviewed but were not included in the table. A total of about 30 patients of Apert syndrome have been described in dermatological literature, acne being the most common dermatological manifestation. Predominant clinical features in all the cases were brachycephaly due to craniosynostosis and syndactyly of hands and feet. Most of the patients had skeletal, dental, gastrointestinal, genitourinary, respiratory, cardiovascular, and dermatological manifestations in varying proportions. Apert syndrome is a rare entity which can present to a dermatologist. It is, therefore, pertinent to be able to diagnose and recognize the various clinical features of this syndrome to ensure timely management of such patients.

Environmental Thermal Stress Induces Neuronal Cell Death and Developmental Malformations in Reptiles

Every stage of organismal life history is being challenged by global warming. Many species are already experiencing temperatures approaching their physiological limits; this is particularly true for ectothermic species, such as lizards. Embryos are markedly sensitive to thermal insult. Here, we demonstrate that temperatures currently experienced in natural nesting areas can modify gene expression levels and induce neural and craniofacial malformations in embryos of the lizard Anolis sagrei. Developmental abnormalities ranged from minor changes in facial structure to significant disruption of anterior face and forebrain. The first several days of post-oviposition development are particularly sensitive to this thermal insult. These results raise new concern over the viability of ectothermic species under contemporary climate change. Herein, we propose and test a novel developmental hypothesis that describes the cellular and developmental origins of those malformations: cell death in the developing forebrain and disruption of normal facial induction due to disrupted Hedgehog signaling. Based on similarities in the embryonic response to thermal stress among distantly related species, we propose that this developmental hypothesis represents a common embryonic response to thermal insult among amniote embryos. Our results emphasize the importance of adopting a broad, multi-disciplinary approach that includes both lab and field perspectives when trying to understand the future impacts of anthropogenic change on animal development.

Incidence of Heart Diseases in Children with Cleft Lip and Cleft Palate

Introduction: Cleft lip and cleft palate are one of the most common craniofacial malformations that occur in children. Congenital heart diseases are more prevalent among children with cleft lip and cleft palate. Early intervention is necessary to improve the survival and for proper development of children. Materials and Methods: A retrospective study is conducted at Paediatrics Department in Saveetha medical College for a period of one year. In the present study medical records of patients with cleft lip and palate are evaluated and analysed for the incidence of heart diseases. Results: In the present study medical records of patients with cleft lip and palate are evaluated and analysed for the incidence of heart diseases. Out of 163 children with cleft lip and cleft palate, 56 children (71.42% male and 28.57% female) had cleft lip, 30 children (66.66% male and 33.33% female) had cleft palate, 77 children (66.23% male and 33.76% female) had both cleft lip and cleft palate.VSD is reported as the most common cardiac anomaly (42.86%) in children with cleft lip and cleft palate. Conclusion: There is an increased incidence of congenital heart diseases in children with cleft lip and cleft palate. Echocardiography is an important investigation done for early identification and proper management.

Mosmo Is Required for Zebrafish Craniofacial Formation

Hedgehog (Hh) signaling is a highly regulated molecular pathway implicated in many developmental and homeostatic events. Mutations in genes encoding primary components or regulators of the pathway cause an array of congenital malformations or postnatal pathologies, the extent of which is not yet fully defined. Mosmo (Modulator of Smoothened) is a modulator of the Hh pathway, which encodes a membrane tetraspan protein. Studies in cell lines have shown that Mosmo promotes the internalization and degradation of the Hh signaling transducer Smoothened (Smo), thereby down-modulating pathway activation. Whether this modulation is essential for vertebrate embryonic development remains poorly explored. Here, we have addressed this question and show that in zebrafish embryos, the two mosmo paralogs, mosmoa and mosmob, are expressed in the head mesenchyme and along the entire ventral neural tube. At the cellular level, Mosmoa localizes at the plasma membrane, cytoplasmic vesicles and primary cilium in both zebrafish and chick embryos. CRISPR/Cas9 mediated inactivation of both mosmoa and mosmob in zebrafish causes frontonasal hypoplasia and craniofacial skeleton defects, which become evident in the adult fish. We thus suggest that MOSMO is a candidate to explain uncharacterized forms of human congenital craniofacial malformations, such as those present in the 16p12.1 chromosomal deletion syndrome encompassing the MOSMO locus.

Quality of life and phonatory and morphological outcomes in cognitively unimpaired adolescents with Pierre Robin sequence: a cross-sectional study of 72 patients

Background Pierre Robin sequence (PRS) is a heterogeneous condition involving retro(micro)gnathia, glossoptosis and upper airway obstruction, very often with posterior cleft palate. Patients with PRS, either isolated or associated with Stickler syndrome have good intellectual prognosis. Nevertheless, the quality of life in adolescence and the phonatory and morphological outcomes are rarely analysed. We assessed the phonatory and morphological outcomes of 72 cognitively unimpaired adolescents with PRS, studied their oral (COHIP-SF19), vocal (VHI-9i) and generic quality of life (QoL; KIDSCREEN-52), and searched for determinants of these outcomes. Results Two-thirds of our adolescents retained low or moderate phonation difficulties, but risk factors were not identified. For 14%, morphological results were considered disharmonious, with no link to neonatal retrognathia severity. Only one vs two-stage surgery seemed to affect final aesthetic results. The oral QoL of these adolescents was comparable to that of control patients and was significantly better than that of children with other craniofacial malformations (COHIP-SF19 = 17.5, 15.4 and 25.7, respectively). The oral QoL of the adolescents with non-isolated PRS was significantly worse (COHIP-SF19 = 24.2) than that of control patients and close to that of children with other craniofacial malformations. The vocal QoL of the adolescents (mean [SD] VHI-9i = 7.5 [5.4]) was better than that of patients with other voice pathologies and better when phonation was good. The generic QoL of the adolescents was satisfactory but slightly lower than that of controls, especially in dimensions concerning physical well-being, relationships and autonomy. QoL results were lower for adolescents with non-isolated than isolated PRS. Only non-isolated PRS and low oral QoL affected generic QoL. Conclusion Morphological or phonatory impairments remain non-rare in adolescents with PRS but do not seem to be directly responsible for altered QoL. These adolescents, especially those with non-isolated PRS, show self-confidence and social-relation fragility. We must focus on long-term functional and psychological results for PRS patients and improve therapy protocols and follow-up, notably those affecting the oral aspects of the disease.

Intraoral scanning of neonates and infants with craniofacial disorders: feasibility, scanning duration, and clinical experience

Summary Objective The aim of this study was to evaluate intraoral scanning (IOS) in infants, neonates, and small children with craniofacial anomalies for its feasibility, scanning duration, and success rate. Impression taking in vulnerable patients can be potentially life-threatening, with the risk of airway obstruction and aspiration of impression material. The advantage of increasingly digitalized dentistry is demonstrated. Materials and methods IOS was captured with the Trios 3® (3Shape, Copenhagen, Denmark) intraoral scanner. The underlying disorders were divided into cleft lip and palate (CLP), Trisomy 21 (T21), Robin Sequence (RS), Treacher Collins syndrome (TC), and isolated mandibular retrognathia (MR). Scan data were analysed by scanning duration, number of images, possible correlations of these factors with the different craniofacial disorders, patient age, and relationship between first and subsequent scans. Clinical experiences with the repeated digital impressions are described. Results Patient data of 141 scans in 83 patients were analysed within an 11-month period. Patients had a median age of 137 days. Median scanning duration was 138 seconds, resulting in a median of 352 images. There was a statistically significant difference in scanning duration (P = 0.001) between infants and neonates. IOS took longest in patients with CLP (537 seconds) and shortest in T21 patients (21 seconds), although there was no statistically significant difference between aetiologies. There was no statistically significant difference between first and subsequent scans in scanning duration. In four cases the IOS had to be repeated, and one patient ultimately required conventional impression taking (all CLP patients; success rate 94%). No severe adverse events occurred. Conclusion IOS is a fast, safe, and feasible procedure for neonates, small children, and infants with craniofacial malformations. One special challenge for both technician and user was identified in patients with CLP, though implementing this new approach of digital impression taking was otherwise found to be highly successful in everyday clinical routine.