DOCSLIB.ORG

Brachycephaly and Syndactyly: Apert's Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Brachycephaly and Syndactyly: Apert's Syndrome Letters to Editor keratinocyte differentiation, it is possible that acitretin may Acne is the most common cutaneous association of Apert’s inhibit viral replication and assembly within the affected syndrome. cells.[3] Oral retinoids have been used with remarkable improvement in the management of extensive and An eight-month-old boy born of nonconsanguineous recalcitrant warts without recurrences.[3,4] parents presented with multiple congenital anomalies. The mother’s antenatal period was uneventful, with no history Epidermodysplasia verruciformis, an inherited disorder of any infectious illness, medication(s) exposure or addiction characterized by widespread and persistent infection with during that period. Family history was non-contributory. HPV, pityriasis versicolor-like lesions and reddish plaques, The patient’s anomalies included craniofacial abnormality has shown dramatic improvement with oral acitretin when and syndactyly of all four limbs. The child had a typical used alone or in combination.[5] Our patient tolerated the facial appearance with a short, wide head (brachycephaly), oral acitretin well with gratifying clinical results without any frontal bossing, retruded (sunken) mid-face, depressed nasal major side effects or recurrences. Hence, oral acitretin can bridge, upward slanting of the eyes, low-set ears and a low be considered as a useful treatment option for extensive posterior hairline [Figure 1]. Examination of the upper and recalcitrant warts. lower limbs showed symmetrical syndactyly leading to the fusion of all the fingers and toes [Figure 2]. The child had DD.. SS.. KKruparupa SShankar,hankar, RRachanaachana SShilpakarhilpakar both growth and mental retardation. Department of Dermatology, Manipal Hospital, Bangalore, India Apert’s syndrome is specifically related to the paternal AAddressddress fforor ccorrespondence:orrespondence: Dr. D. S. Krupa Shankar, Head of Department, Department of Dermatology, Manipal Hospital, 98, age effect having a frequency of one in every 65,000 live Rustom Bagh, Airport Road, Bangalore 560017, India, Email: [email protected] RREFERENCESEFERENCES 1. Laurent R, Kienzler JL. Epedemilology of HPV infection. Clin Dermatol 1985;3:64-70. 2. Massing AM, Epstein WL. Natural history of warts. A two year study. Arch Dermatol 1963;87:306-10. 3. Choi YL, Lee KJ, Kim WS, Lee DY, Lee JH, Lee ES, et al. Treatment of extensive and recalcitrant viral warts with acitretin. Int J Dermatol 2006;45:480-2. 4. Gelmetti C, Cerri D, Schiuma AA, Menni S. 20 children with extensive warts were given Etretinate 1mg/kg/day for 3months. Pediatr Dermatol 1987;4:254-8. 5. Anadolu R, Oskay T, Erdem C, Boyvat A, Terzi E, Gurgey E. Treatment of epidermodysplasia verruciformis with a Figure 1: Typical facial dysmorphosis combinationof acitretin and interferon alfa-2a. J Am Acad Dermatol 2001;45:296-9. BBrachycephalyrachycephaly andand syndactyly:syndactyly: AApert’spert’s ssyndromeyndrome Sir, Apert’s syndrome (acrocephalosyndactyly type 1) is a rare malformation syndrome first described by Wheaton in 1894, and later by Apert in 1906.[1] It is characterized by craniosynostosis associated with maxillary hypoplasia, symmetric syndactyly of the hands and feet, and other systemic malformations including mental retardation. Figure 2: Deformities in feet Indian J Dermatol Venereol Leprol | July-August 2008 | Vol 74 | Issue 4 395 Letters to Editor births; the affected patients generally do not survive AAddressddress fforor ccorrespondence:orrespondence: Prof. Amrinder J. Kanwar, Department [1] of Dermatology, Postgraduate Institute of Medica l Education and beyond infancy. In those patients who reach adolescence, Research, Chandigarh-160 012, India. acne is an important cutaneous manifestation. Most cases E-mail: [email protected] are sporadic, although autosomal dominant inheritance as well as germinal mosaicism have been reported.[2] The RREFERENCESEFERENCES syndrome is caused by nucleotide alterations resulting in amino acid substitutions, leading to a mutation in the 1. Cohen MM Jr, Kreiborg S, Lammer EJ, Cordero JF, fibroblast growth factor receptor-2 (FGFR-2) gene mapped Mastroiakovo P, Ericson JD, et al. Birth prevalence study of to chromosome 10q26.[3] Premature fusion of the bones is the Apert syndrome. Am J Med Genet 1992;42:655-9. 2. Allanson JE. Germinal mosaicism in Apert syndrome. Clin responsible for bony abnormalities; premature fusion of Genet 1986;29:429-33. coronal sutures lead to brachycephaly. Other craniofacial 3. Hollway GE, Suthers GK, Haan EA, Thompson E, David DJ, abnormalities include a prominent forehead with skin Gecz J, et al. Mutation detection in FGFR2 craniosynostosis wrinkling, a broad cranium, and a flat occiput. The syndromes. Hum Genet 1997;99:251-5. shortened bony orbit leads to hypertelorism, proptosis 4. Munro CS, Wilkie AO. Epidermal mosaicism producing and strabismus. Additional features include a short broad localized acne: somatic mutation in FGFR2. Lancet nose with a bulbous tip, micrognathia, and a cleft palate. 1998;352:704-5. Intracranial anomalies include megalocephaly, progressive hydrocephalus, hypoplastic white matter, and agenesis of the corpus callosum and limbic structures, leading to HHydroxychloroquineydroxychloroquine versusversus cognitive impairment. Cardiac abnormalities including atrial and ventricular septal defects and renal anomalies such as cchloroquinehloroquine inin polymorphicpolymorphic lightlight hydronephrosis occur in about 10% of these patients. eeruptionruption The cutaneous abnormalities reported are acne, hyperhidrosis and oculocutaneous albinism. Acne is now Sir, known to represent the dermatological hallmark of Apert’s We read the article titled “Comparative study of efficacy and syndrome; it usually appears between the age of nine and safety of hydroxychloroquine and chloroquine in polymorphic 12 years. The acneiform lesions involve not only the face light eruption: A randomized, double-blind, multicentric and upper trunk, but also affect the forearms, buttocks, and study” with great interest. However, we wish to point out thighs. Oily skin is striking by the time of adolescence but the the following incongruities observed in this study. etiology of these acneiform lesions remains controversial. Increases in circulatory androgens or the density of sebaceous The conclusion drawn about superior efficacy and tolerability gland androgen receptors have not been documented. End- of hydroxychloroquine over chloroquine is not corroborated organ androgen metabolism defects, structural malformation by the findings of the study, where only a marginal difference of pilosebaceous apparatus and a role of FGFR-2 in regulating was observed in the efficacy of the two drugs, and in fact, androgen sensitivity of the pilosebaceous unit have been chloroquine fared better in the side effect profile.[1] suggested hypotheses for the acneiform lesions.[4] The skin, eyes and hair may show pigmentary dilution. Other Negative serological tests for light eruption (LE) are occasional cutaneous abnormalities include interrupted pertinent and desirable for the diagnosis of polymorphic eyebrows, forehead wrinkling, paronychial infections, skin light eruption (PLE) patients as PLE and LE may often coexist dimpling over the knuckles, shoulders and elbows, as well and PLE precedes LE in a subset of the patients.[2,3] as lateral plantar hyperkeratosis. The lack of ocular toxicity observed in the hydroxychloroquine There is no definitive treatment for this syndrome. The treatment group after a short course of therapy is prognosis varies from child to child and a multidisciplinary understandable as the same is expected after long-term approach is recommended. use only. The important risk factors for ocular toxicity associated with hydroxychloroquine therapy are: excessive DDipankaripankar DDe,e, TarunTarun NNarang,arang, AmrinderAmrinder J KKanwar,anwar, daily dosage, increasing cumulative dosage, the duration of SSunilunil DDograogra Department of Dermatology, Postgraduate Institute of Medical treatment and the patient’s age as well as coexistent renal Education and Research, Chandigarh-160 012, India or liver disease and concomitant retinal disease.[4,5] 396 Indian J Dermatol Venereol Leprol | July-August | Vol 74 | Issue 4.
Load more

Recommended publications
  • Syndromic and Complex Craniosynostosis: Craniosynostosis: and Complex Syndromic
    Syndromic and Complex Craniosynostosis: Craniosynostosis: and Complex Syndromic Uitnodiging Voor het bijwonen van de openbare verdediging van het proefschrift Syndromic and Complex Craniosynostosis: Skull and brain abnormalities Syndromic and Complex Craniosynostosis: in relation to intracranial hypertension Skull and brain abnormalities in relation to intracranial hypertension door Bianca F.M. Rijken Bianca F. M. Rijken Skull and brain abnormalities in relation to intracranial hypertension intracranial to abnormalitiesSkull in relation and brain op vrijdag 8 april 2016 om 13:30 uur Senaatszaal, Erasmus Building Erasmus Universiteit Rotterdam Burgemeester Oudlaan 50 3062 PA Rotterdam Na afloop van de promotie bent u van harte uitgenodigd voor de receptie Bianca F.M. Rijken De Ruyterstraat 10b 3071 PJ Rotterdam [email protected] 06-33148619 Paranimfen Sun-Jine van Bezooijen [email protected] 06-33048922 Hoa Ha [email protected] 06-14911149 Bianca F. M. Rijken Bianca F. Syndromic and Complex Craniosynostosis: Skull and brain abnormalities in relation to intracranial hypertension Bianca F. M. Rijken ISBN 978-94-6299-319-8 Layout & printing Ridderprint BV - www.ridderprint.nl Cover design Ridderprint BV - www.ridderprint.nl Copyright 2016 Bianca Francisca Maria Rijken All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without prior permission of the author. Sponsors: Syndromic and Complex Craniosynostosis: Skull and brain abnormalities in relation to intracranial hypertension Syndromale en complexe craniosynostose: Schedel en brein afwijkingen in relatie tot intracraniële hypertensie Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr.
    [Show full text]
  • Letter to Editor Sep 2012; Vol 22 (No 3), Pp: 432-433
    Iran J Pediatr Letter to Editor Sep 2012; Vol 22 (No 3), Pp: 432-433 pregnancy. First born baby died at the age of 10 Isolated Lower Limb Phocomelia – a Rare postnatal day, cause is unknown, but he was Limb Malformation apparently not having any congenital malformation. Physical examination revealed weight 4.8 kg, length 54.5 cm, head Priyanka Bansal*, MD; Akhil Bansal, MD, and Shitalmala Devi, MD circumference 36.5 cm, no facial dysmorphism, spine normal. Only deformity was phocomelia of Jawaharlal Nehru Medical College, Department of Pathology, left lower limb (Fig. 1). Systemic examination India was normal. X ray pelvis with both lower limbs Received: Jan 29, 2011; Accepted: Mar 24, 2012 showed left lower limb showed absent femur, tibia and fibula, a single tarsal bone visualized, Phocomelia, ie the absence or severe hypoplasia distal foot appears grossly normal. Right hip and of the long tubular bones with more or less femur do not reveal any abnormality. Chest X ray intact hands and or feet, is widely known to be was absolutely normal and abdominal the most spectacular finding of thalidomide sonography abdomen and cranianl showed no embryopathy[1]. It may be complete in the form abnormality. 2-dimensional echocardiography that proximal and distal bones of limb are absent was done to rule out congenital heart defect, or may be incomplete when either proximal or which was also normal. distal bones are missing. It is known to occur in Phocomelia[2] in the complete form, the arm some familial syndromes such as Roberts and forearm are absent in the upper limb and syndrome[10], the DK Phocomelia syndrome[8] the thigh and leg are absent in the lower limb and in a few other extremely rare syndromes.
    [Show full text]
  • Medically Necessary Orthodontic Treatment – Dental
    UnitedHealthcare® Dental Coverage Guideline Medically Necessary Orthodontic Treatment Guideline Number: DCG003.08 Effective Date: November 1, 2020 Instructions for Use Table of Contents Page Related Medical Policy Coverage Rationale ....................................................................... 1 • Orthognathic (Jaw) Surgery Definitions ...................................................................................... 1 Applicable Codes .......................................................................... 3 Description of Services ................................................................. 3 References ..................................................................................... 3 Guideline History/Revision Information ....................................... 4 Instructions for Use ....................................................................... 4 Coverage Rationale Orthodontic treatment is medically necessary when the following criteria have been met: All services must be approved by the plan; and The member is under the age 19 (through age 18, unless the member specific benefit plan document indicates a different age); and Services are related to the treatment of a severe craniofacial deformity that results in a physically Handicapping Malocclusion, including but not limited to the following conditions: o Cleft Lip and/or Cleft Palate; o Crouzon Syndrome/Craniofacial Dysostosis; o Hemifacial Hypertrophy/Congenital Hemifacial Hyperplasia; o Parry-Romberg Syndrome/Progressive Hemifacial Atrophy;
    [Show full text]
  • Radial, Renal and Craniofacial Anomalies: Baller-Gerold Syndrome
    Published online: 2020-01-15 Free full text on www.ijps.org Case Report Radial, renal and craniofacial anomalies: Baller-Gerold syndrome Jyotsna Murthy, Ramesh Babu1, Padmasani Venkat Ramanan2 Department of Plastic Surgery, Director of Cleft and Craniofacial Center, 1Consultant Pediatric Urologist, 2Department of Pediatrics, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, Tamil Nadu, India Address for correspondence: Dr. Jyotsna Murthy, Department of Plastic Surgery, Sri Ramachandra Medical College and Research Institute, Porur, Chennai - 600 116, Tamil Nadu, India. E-mail: [email protected] ABSTRACT The Baller-Gerold syndrome is a rare syndrome with very few cases published in literature. Craniosynostosis and radial aplasia are striking features, easy to diagnose. However, there are many differential diagnoses. Often, the question raised is whether the Baller-Gerald syndrome is a distinct entity. We report a patient with Þ ndings of craniosynostosis and radial aplasia consistent with the diagnosis of the Baller-Gerold syndrome. Genotypic heterogeneity could possibly underlie the phenotypic variability exhibited by these cases. KEY WORDS Baller-Gerold syndrome, craniosynostosis, crossed ectopia, ectopic kidneys, microcephaly, radial agenesis, radial club hand, reß ux, renal agenesis, vesico ureteric reß ux INTRODUCTION anal (imperforated anus, anterior anus, perineal fistulae), nervous system (polymicrogria, hydrocephalus, agenesis aller[1] described a female with oxycephaly and of corpus callosum or seizure disorder) and skeletal absent radius whose parents were third cousins. (joint limitation, rib fusion, flat vertebrae and absent BGerold[2] described a brother and sister, aged middle phalanx). They are divided into two groups - those 16 years and two days, respectively with tower skull, with craniosynostosis and radial defect alone and those radial aplasia and small ulna.
    [Show full text]
  • Prenatal Ultrasonography of Craniofacial Abnormalities
    Prenatal ultrasonography of craniofacial abnormalities Annisa Shui Lam Mak, Kwok Yin Leung Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital, Hong Kong SAR, China REVIEW ARTICLE https://doi.org/10.14366/usg.18031 pISSN: 2288-5919 • eISSN: 2288-5943 Ultrasonography 2019;38:13-24 Craniofacial abnormalities are common. It is important to examine the fetal face and skull during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal Received: May 29, 2018 skull and face can increase the detection rate. When an abnormality is found, it is important Revised: June 30, 2018 to perform a detailed scan to determine its severity and search for additional abnormalities. Accepted: July 3, 2018 Correspondence to: The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and Kwok Yin Leung, MBBS, MD, FRCOG, craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, Cert HKCOG (MFM), Department of micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic Obstetrics and Gynaecology, Queen Elizabeth Hospital, Gascoigne Road, techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some Kowloon, Hong Kong SAR, China syndromes is feasible if the family history is suggestive. Tel. +852-3506 6398 Fax. +852-2384 5834 E-mail: [email protected] Keywords: Craniofacial; Prenatal; Ultrasound; Three-dimensional ultrasonography; Fetal structural abnormalities This is an Open Access article distributed under the Introduction terms of the Creative Commons Attribution Non- Commercial License (http://creativecommons.org/ licenses/by-nc/3.0/) which permits unrestricted non- Craniofacial abnormalities are common.
    [Show full text]
  • Lingual Agenesis: a Case Report and Review of Literature
    Research Article Clinics in Surgery Published: 09 Mar, 2018 Lingual Agenesis: A Case Report and Review of Literature Mark Enverga, Ibrahim Zakhary* and Abraham Khanafer Department of Oral and Maxillofacial Surgery, University of Detroit Mercy, School of Dentistry, USA Abstract Aglossia is a rare condition characterized by the complete absence of the tongue. Its etiology is still unknown. The underlying pathophysiology involves disruption of the development of the lateral lingual swellings and tuberculum impar during the second month of gestation. In this case report, a 26-year old African American female with aglossia presented to the Detroit Mercy Oral Surgery Clinic. The patient presented for extraction of tooth #28, which was located within a fused bony plate at the floor of the mandible. This study presents a case of aglossia, as well as a critical review of aglossia in current literature. Introduction Aglossia is a rare condition characterized by the complete absence of the tongue. The exact etiology of aglossia is still unknown. Possible etiologic factors during embryogenesis include maternal febrile illness, drug ingestion, hypothyroidism, and cytomegalovirus infection. Heat-induced vascular disruption in the fourth embryonic week and chronic villous sampling performed before 10 weeks of amenorrhea, also called the disruptive vascular hypothesis, may be another possible cause of aglossia [1,2]. The underlying pathophysiology involves disruption of the normal embryogenic development of the lateral lingual swellings and tuberculum impar during the second month of gestation [3]. Most cases of aglossia are associated with other congenital limb malformations and craniofacial abnormalities, such as hypodactyly, adactyly, cleft palate, Pierre Robin sequence, Hanhart syndrome, Moebius syndrome, and facial nerve palsy.
    [Show full text]
  • Three-Dimensional Ultrasound Study of Fetal Craniofacial Anatomy
    Three-dimensional ultrasound study of fetal craniofacial anatomy N.M. Roelfsema The work presented in this thesis was financially supported by the Netherlands Organization for Scientific Research, grand no: 902-37-116. It was conducted at the department of Obstet- rics and Gynecology and in collaberation with the department of Plastic and Reconstructive Surgery, Erasmus MC, Rotterdam, The Netherlands J.E. Jurriaanse Stichting and GE Healthcare financially supported the printing of this thesis The following parts of this publication have been published previously and have been repro- duced with permission from the publishers: Elsevier Ltd.(Roelfsema et al. Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy. Am J Obstet Gynecol 2004;190:275-80) and the International Society of Ultrasound in Obstet- rics and Gynecology (Roelfsema et al. Three-dimensional ultrasonography of prenatal skull base development. Ultrasound Obstet Gynecol 2007:29:372-7; Roelfsema et al. Craniofacial variability index determined by three-dimensional ultrasound in isolated versus syndromal cleft lip/palate. Ultrasound Obstet Gynecol 2007;29:265-70; Roelfsema et al. Craniofacial variability index in utero; a three-dimensional ultrasound study. Ultrasound Obstet Gynecol 2007;29:258-64; Roelfsema et al. Three-dimensional sonographic determination of normal fetal mandibular and maxillary development during the second half of pregnancy. Ultrasound Obstet Gynecol 2006;28:950-7; Dikkeboom et al. The role of three-dimensional ultrasound in visualizing the fetal cranial sutures and fontanels during the second half of pregnancy. Ultra- sound Obstet Gynecol 2004;24:412-6). Front cover: © N.M. Roelfsema © 2007, N.M.
    [Show full text]
  • Attenuation of Signaling Pathways Stimulated by Pathologically Activated FGF-Receptor 2 Mutants Prevents Craniosynostosis
    Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis V. P. Eswarakumar*, F. Ozcan*¨ †, E. D. Lew*, J. H. Bae*, F. Tome´ *, C. J. Booth‡, D. J. Adams§, I. Lax*, and J. Schlessinger*¶ *Department of Pharmacology and ‡Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520; and §Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030 Contributed by J. Schlessinger, October 19, 2006 (sent for review September 22, 2006) Craniosynostosis, the fusion of one or more of the sutures of the heparin/FGFR complex results in FGFR dimerization and ac- skull vault before the brain completes its growth, is a common (1 tivation (11–14). The Crouzon Cys342Tyr mutation disrupts the in 2,500 births) craniofacial abnormality, Ϸ20% of which occur- structure of D3, abrogating the ligand-binding capacity of the rences are caused by gain-of-function mutations in FGF receptors extracellular domain of FGFR2c. In addition, Cys-278, which (FGFRs). We describe a genetic and pharmacological approach for normally forms an intramolecular disulfide bond with Cys-342, the treatment of a murine model system of Crouzon-like cranio- becomes unpaired. The unpaired Cys-278 instead forms a disul- synostosis induced by a dominant mutation in Fgfr2c. Using ge- fide bond with Cys-278 of a neighboring similarly mutated netically modified mice, we demonstrate that premature fusion of FGFR2c molecule intermolecularly resulting in the formation of sutures mediated by Crouzon-like activated Fgfr2c mutant is pre- constitutively activated stable homodimers that are unable to vented by attenuation of signaling pathways by selective uncou- bind FGF (9, 10, 15).
    [Show full text]
  • Dissociated Eye Movements in Craniosynostosis: a Hypothesis Revived Br J Ophthalmol: First Published As 10.1136/Bjo.77.9.563 on 1 September 1993
    BritishJournal ofOphthalmology 1993; 77: 563-568 563 Dissociated eye movements in craniosynostosis: a hypothesis revived Br J Ophthalmol: first published as 10.1136/bjo.77.9.563 on 1 September 1993. Downloaded from H Cheng, M A Burdon, G A Shun-Shin, S Czypionka Abstract quently in our clinic. Coronal synostosis, charac- A characteristic pattern of dissociated eye teristic of these patients, results in lack of bone movements was observed in a large proportion growth in the anteroposterior direction and of our patients with a variety of cranio- brachycephaly. Mid-facial hypoplasia and synostosis syndromes. These anomalies simu- underdevelopment ofthe base ofthe skull lead to late overaction of the inferior oblique and shallowing of the orbit and proptosis, while underaction of the superior oblique muscles compensatory lateral expansion of the cranium which, however, cannot fully explain the predisposes to hypertelorism and orbital diver- abnormalities. In a number of cases, gence. excyclorotation of the muscle cone was The many ocular abnormalities that have been observed, with the upper pole of the eye tilted described23 in this group of patients can be away from the midline. It is postulated that divided into three main groups: those involving such excyclorotation of the eyes will lead to the optic nerve, those due to proptosis or expo- dissociated eye movements which can be sure, and motility abnormalities including explained on physiological grounds according squints, of which exotropia is common; Thus, to Hering's law. This paper presents a review Pruzansky3 and Choy4 both reported a 50% of our patients and evidence to support this prevalence, or more, of exophoria in patients hypothesis.
    [Show full text]
  • Craniofacial Diseases Caused by Defects in Intracellular Trafficking
    G C A T T A C G G C A T genes Review Craniofacial Diseases Caused by Defects in Intracellular Trafficking Chung-Ling Lu and Jinoh Kim * Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-515-294-3401 Abstract: Cells use membrane-bound carriers to transport cargo molecules like membrane proteins and soluble proteins, to their destinations. Many signaling receptors and ligands are synthesized in the endoplasmic reticulum and are transported to their destinations through intracellular trafficking pathways. Some of the signaling molecules play a critical role in craniofacial morphogenesis. Not surprisingly, variants in the genes encoding intracellular trafficking machinery can cause craniofacial diseases. Despite the fundamental importance of the trafficking pathways in craniofacial morphogen- esis, relatively less emphasis is placed on this topic, thus far. Here, we describe craniofacial diseases caused by lesions in the intracellular trafficking machinery and possible treatment strategies for such diseases. Keywords: craniofacial diseases; intracellular trafficking; secretory pathway; endosome/lysosome targeting; endocytosis 1. Introduction Citation: Lu, C.-L.; Kim, J. Craniofacial malformations are common birth defects that often manifest as part of Craniofacial Diseases Caused by a syndrome. These developmental defects are involved in three-fourths of all congenital Defects in Intracellular Trafficking. defects in humans, affecting the development of the head, face, and neck [1]. Overt cranio- Genes 2021, 12, 726. https://doi.org/ facial malformations include cleft lip with or without cleft palate (CL/P), cleft palate alone 10.3390/genes12050726 (CP), craniosynostosis, microtia, and hemifacial macrosomia, although craniofacial dys- morphism is also common [2].
    [Show full text]
  • Letter to Editor Sep 2012; Vol 22 (No 3), Pp: 432-433
    Iran J Pediatr Letter to Editor Sep 2012; Vol 22 (No 3), Pp: 432-433 Isolated Lower Limb Phocomelia – a Rare Limb Malformation pregnancy. First born baby died at the age of 10 postnatal day, cause is unknown, but he was apparently not having any congenital Priyanka Bansal*, MD; Akhil Bansal, MD, and malformation. Physical examination revealed Shitalmala Devi, MD weight 4.8 kg, length 54.5 cm, head circumference 36.5 cm, no facial dysmorphism, spine normal. Only deformity was phocomelia of Jawaharlal Nehru Medical College, Department of Pathology, India Jan 29, 2011 Mar 24, 2012 left lower limb (Fig. 1). Systemic examination was normal. X ray pelvis with both lower limbs Received: ; Accepted: showed left lower limb showed absent femur, tibia and fibula, a single tarsal bone visualized, Phocomelia, ie the absence or severe hypoplasia distal foot appears grossly normal. Right hip and of the long tubular bones with more or less femur do not reveal any abnormality. Chest X ray intact hands and or feet, is widely known to be was absolutely normal and abdominal the most spectacular[1] finding of thalidomide sonography abdomen and cranianl showed no embryopathy . It may be complete in the form abnormality. 2-dimensional echocardiography that proximal and distal bones of limb are absent was done to rule out congenital heart defect, or may be incomplete when either proximal or which was also[2] normal. distal bones are missing. It is known to occur in Phocomelia in the complete form, the arm some familial[10] syndromes such as Roberts[8] and forearm are absent in the upper limb and syndrome , the DK Phocomelia syndrome the thigh and leg are absent in the lower limb and in a few other extremely rare syndromes.
    [Show full text]
  • Inactivation of Sonic Hedgehog Signaling and Polydactyly in Limbs of Hereditary Multiple Malformation, a Novel Type of Talpid Mutant
    ORIGINAL RESEARCH published: 27 December 2016 doi: 10.3389/fcell.2016.00149 Inactivation of Sonic Hedgehog Signaling and Polydactyly in Limbs of Hereditary Multiple Malformation, a Novel Type of Talpid Mutant Yoshiyuki Matsubara 1 †, Mikiharu Nakano 2 †, Kazuki Kawamura 1 †, Masaoki Tsudzuki 3, Jun-Ichi Funahashi 4, Kiyokazu Agata 5, Yoichi Matsuda 2, 6, Atsushi Kuroiwa 1 and Takayuki Suzuki 1* 1 Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan, 2 Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan, 3 Laboratory of Animal Breeding and Genetics, Graduate School of Biosphere Science, Hiroshima University, Hiroshima, Japan, 4 Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan, 5 Department of Biophysics, Graduate School of Science, Kyoto University, 6 Edited by: Kyoto, Japan, Laboratory of Animal Genetics, Department of Applied Molecular Biosciences, Graduate School of Takaaki Matsui, Bioagricultural Sciences, Nagoya University, Nagoya, Japan Nara Institute of Science and Technology, Japan Hereditary Multiple Malformation (HMM) is a naturally occurring, autosomal recessive, Reviewed by: hmm−/− Minoru Omi, homozygous lethal mutation found in Japanese quail. Homozygote embryos ( ) 2 3 Fujita Health University, Japan show polydactyly similar to talpid and talpid mutants. Here we characterize the Joseph Lancman, molecular profile of the hmm−/− limb bud and identify the cellular mechanisms that Sanford Burnham Prebys Medical −/− Discovery Institute, USA cause its polydactyly. The hmm limb bud shows a severe lack of sonic hedgehog *Correspondence: (SHH) signaling, and the autopod has 4 to 11 unidentifiable digits with syn-, poly-, and Takayuki Suzuki brachydactyly. The Zone of Polarizing Activity (ZPA) of the hmm−/− limb bud does [email protected] not show polarizing activity regardless of the presence of SHH protein, indicating that †These authors have contributed equally to this work.
    [Show full text]