DOCSLIB.ORG

Rare Syndromes Associated with Infertility Hempel M, Buchholz T J

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rare Syndromes Associated with Infertility Hempel M, Buchholz T J Journal für Reproduktionsmedizin und Endokrinologie – Journal of Reproductive Medicine and Endocrinology – Andrologie • Embryologie & Biologie • Endokrinologie • Ethik & Recht • Genetik Gynäkologie • Kontrazeption • Psychosomatik • Reproduktionsmedizin • Urologie Rare Syndromes Associated with Infertility Hempel M, Buchholz T J. Reproduktionsmed. Endokrinol 2009; 6 (1), 24-26 www.kup.at/repromedizin Online-Datenbank mit Autoren- und Stichwortsuche Offizielles Organ: AGRBM, BRZ, DVR, DGA, DGGEF, DGRM, D·I·R, EFA, OEGRM, SRBM/DGE Indexed in EMBASE/Excerpta Medica/Scopus Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft, A-3003 Gablitz FERRING-Symposium digitaler DVR 2021 Mission possible – personalisierte Medizin in der Reproduktionsmedizin Was kann die personalisierte Kinderwunschbehandlung in der Praxis leisten? Freuen Sie sich auf eine spannende Diskussion auf Basis aktueller Studiendaten. SAVE THE DATE 02.10.2021 Programm 12.30 – 13.20Uhr Chair: Prof. Dr. med. univ. Georg Griesinger, M.Sc. 12:30 Begrüßung Prof. Dr. med. univ. Georg Griesinger, M.Sc. & Dr. Thomas Leiers 12:35 Sind Sie bereit für die nächste Generation rFSH? Im Gespräch Prof. Dr. med. univ. Georg Griesinger, Dr. med. David S. Sauer, Dr. med. Annette Bachmann 13:05 Die smarte Erfolgsformel: Value Based Healthcare Bianca Koens 13:15 Verleihung Frederik Paulsen Preis 2021 Wir freuen uns auf Sie! Rare Syndromes in Infertility Rare Syndromes Associated with Infertility M. Hempel, T. Buchholz Although rare syndromes seldomly are the reason for infertility, physicians for reproductive medicine should be aware of these syndromes. The majority of syndromes can be diagnosed clinically by thorough exploration of the personal and family histories and by extensive medical examination. To confirm a genetic diagnosis, specific tests have to be carried out. If a syndrome is detected, it often explains not only the reproductive failure but also other possible disabilities, leading to a specific therapy and accurate genetic counseling of the affected, patient and his family. J Reproduktionsmed Endokrinol 2009; 6 (1): 24–6. Key words: hypogonadotropic hypogonadism, maldescended testes, primary infertility, syndromes, genetic counseling Introduction • Rare syndromes associated with mal- because sometimes patients with the descended testes Kallmann syndrome are not aware that Infertility is not commonly associated • Rare syndromes associated with pri- they have anosmia. Additional symp- with the occurrence of genetic syn- mary infertility. toms include eunuchoidism, cleft lip/ dromes [1]. Therefore, infertility work- palate, reduced hearing ability, unilat- up does not center on the detection of eral agenesis of a kidney, brachydactyly, rare syndromes. However, these syn- Rare Syndromes Associa- synkinesia, and agenesis of the corpus dromes can be found through a detailed ted with Hypogonadotro- callosum. and targeted personal and family history pic Hypogonadism examination, including a three-genera- Autosomal dominant, X-chromosomal tion pedigree, and through an accurate Hypogonadotropic hypogonadism causes recessive and autosomal recessive in- clinical examination. If a syndrome is infertility, which can be successfully heritance of the Kallmann syndrome has suspected, further investigations should treated by gonadotropin stimulation. been described (Tab. 1). In affected be initiated. There are a few syndromes which have families, the pattern of inheritance can the leading symptom of hypogonado- be distinguished according to the pedi- More than 70 syndromes associated with tropic hypogonadism. gree. Mutations in the KAL1 gene lo- infertility have been found so far. The cated on the short arm of the X chromo- majority of these syndromes is ex- Kallmann syndrome (olfactogenital syn- some have been found in 5–10 % of male tremely rare and related to severe mal- drome, anosmia with hypogonadotropic Kallmann patients. Mutations in the formations and mental retardation. Due hypogonadism) occurs in males with an FGFR1 gene have been detected in 5– to their handicaps infertility is not their incidence of 1:8000. Females can also be 10 % of autosomal dominant Kallmann main problem because mostly these pa- affected, but less frequently with an inci- syndrome patients. More infrequent mu- tients do not consider family planning. dence of 1:40,000 [3]. Cardinal symp- tations in the PROKR2 gene (~5 %) and In some syndromes, however, infertility toms of the Kallmann syndrome are the the PROK2 gene (< 5 %) have also been may be the initial obvious symptom [2]. inability to smell and hypogonadotropic revealed leading to the autosomal domi- Other symptoms can be minor and are hypogonadism. The patient has to be nant Kallmann syndrome. There is at not easily recognizable or will develop asked if he has difficulty in smelling least one more gene locus suspected of later in life. It is not the purpose of this article to list Table 1: Molecular genetics and phenotypic association in the Kallmann syndrome all syndromes which are accompanied by infertility. Some examples of rare but X-linked recessive Autosomal dominant Autosomal recessive widely recognizable syndromes are de- Kallmann syndrome Kallmann syndrome Kallmann syndrome scribed here to illustrate the importance Mutation in KAL1 gene Mutation in FGFR1 gene Gene loci unknown of the medical history and examination (5–10 %) (5–10 %) Deletion of KAL1 gene Mutation in PROKR2 gene of the patient. (infrequent) (5 %) Mutation in PROK2 gene Among rare syndromes associated with (< 5 %) infertility it is helpful to differentiate be- Delayed pubertal development, Cleft lip/palate, oligodontia, tween: micropenis, maldescended digit malformation, • Rare syndromes associated with hypo- testes, synkinesia, unilateral synkinesia, agenesis of gonadotropic hypogonadism renal agenesis corpus callosum Received: January 8, 2009; accepted after revision: February 3, 2009 From the Institut für Humangenetik, Technische Universität München, Germany Correspondence: Dr. med. Maja Hempel, Institut für Humangenetik, Technische Universität München, D-81675 München, Trogerstraße 32; e-mail: [email protected] 24 J Reproduktionsmed Endokrinol 2009; 6 (1) For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. Rare Syndromes in Infertility Table 2: Testing algorithm in the variability of Bardet-Biedel syndrome is cranial dysostosis (hypoplasia of the cla- Kallmann syndrome very high. viculae, craniosynostosis), Bloom’s syn- drome (short stature, teleangiectatic ery- In family cases thematous skin lesions, high risk for ma- In X-linked pattern of inheritance Rare Syndromes Associa- lignancies), and Russel-Silver syndrome 1. Sequencing of KAL1 gene ted with Maldescended (short stature, relative macrocephaly, 2. Deletion screening of KAL1 gene distinctive face, hemihypertrophy) [10]. In autosomal dominant pattern of inheritance Testes 1. Sequencing of FGFR1 gene These syndromes are usually detected 2. Sequencing of PORKR2 and PROK2 gene There are a number of syndromes associ- early in infancy. However, because these ated with maldescended testes. One ex- patients are not severely handicapped, In isolated cases ample is the Noonan syndrome in males they may desire children and therefore Male (pterygium colli syndrome, male Turner seek reproductive counseling for infer- 1. Sequencing of KAL1 gene 2. Sequencing of FGFR1 gene syndrome). This syndrome is character- tility problems. 3. Sequencing of PROKR2 and PROK2 gene ized by a congenital heart defect (espe- Female cially pulmonary valvular stenosis, dys- 1. Sequencing of FGFR1 gene plastic pulmonary valve, and hyper- Rare Syndromes Associa- 2. Sequencing of PROKR2 and PROK2 gene trophic cardiomyopathy), short stature, ted with Primary Infertility and a typical sternum malformation contributing to this syndrome, especially (pectus carinatum in cranial and pectus Primary Ciliary Dyskinesia (PCD) is a for the autosomal recessivly inherited excavatum in the caudal part of the ster- rare entity caused by congenital defects Kallmann syndrome [3–5]. The algo- num). Furthermore, these patients ex- in cilia, which includes the immotile rithm for genetic testing depends on the hibit a typical facial dysmorphism in- cilia syndrome, Kartagener syndrome, inheritance pattern and gender (Tab. 2). cluding hypertelorism, ptosis, down- ciliary dysmotility, and primary orienta- In males with sporadic Kallmann syn- slanting palpebral fissures, deep-set and tion defects. Main symptoms of PCD are drome or patients with suspected X- posterior rotated ears, short and broad recurrent and persistent rhinitis, nasal linked inheritance, the KAL1 gene should neck, and low posterior hair line. Some, polyps, recurrent ear infections, tym- be sequenced first. In females with the but not all patients suffer from mild to panosclerosis, bronchiectasis, and infer- sporadic Kallmann syndrome and pa- moderate mental retardation, depending tility. Situs inversus occurs in 50 % of tients with an autosomal dominant pat- on the underlying genetic defect [7–9]. patients with PCD, named Kartagener tern of inheritance, KAL1 gene analysis Infertility is not the leading symptom of syndrome. Additionally, PCD patients can be omitted. Instead, the order of gene Noonan syndrome but may occur as a may suffer from ceratoconus, glaucoma, sequencing should be as follows: first result of untreated maldescended testes. and myopia as well as from malforma- the FGFR1 gene, secondly the PROKR2 With an incidence
Load more

Recommended publications
  • MR Imaging of Kallmann Syndrome, a Genetic Disorder of Neuronal Migration Affecting the Olfactory and Genital Systems
    MR Imaging of Kallmann Syndrome, a Genetic Disorder of Neuronal Migration Affecting the Olfactory and Genital Systems 1 2 2 3 4 Charles L. Truwit, ' A. James Barkovich, Melvin M. Grumbach, and John J. Martini PURPOSE: We report the MR findings in nine patients with clinical and laboratory evidence of Kallmann syndrome (KS), a genetic disorder of olfactory and gonadal development. In patients with KS, cells that normally express luteinizing hormone-releasing hormone fail to migrate from the medial olfactory placode along the terminalis nerves into the forebrain. In addition, failed neuronal migration from the lateral olfactory placode along the olfactory fila to the forebrain results in aplasia or hypoplasia of the olfactory bulbs and tracts. Patients with KS, therefore, suffer both reproductive and olfactory dysfunction. METHODS: Nine patients with KS underwent direct coronal MR of their olfactory regions in order to assess the olfactory sulci, bulbs, and tracts. A lOth patient had MR findings of KS, although the diagnosis is not yet confirmed by laboratory tests. RESULTS: Abnormalities of the olfactory system were identified in all patients. In particular, the anterior portions of the olfactory sulci were uniformly hypoplastic. The olfactory bulbs and tracts appeared hypoplastic or aplastic in all patients in whom the bulb/ tract region was satisfactorily imaged. In two (possibly three) patients, prominent soft tissue in the region of the bulbs suggests radiographic evidence of neurons that have been arrested before migration. CONCLUSIONS: Previous investigators of patients with KS used axial MR images to demonstrate hypoplasia of the olfactory sulci but offered no assessment of the olfactory bulbs.
    [Show full text]
  • Segmental Overvekst Og Vaskulærmalformasjoner V02
    2/1/2021 Segmental overvekst og vaskulærmalformasjoner v02 Avdeling for medisinsk genetikk Segmental overvekst og vaskulærmalformasjoner Genpanel, versjon v02 * Enkelte genomiske regioner har lav eller ingen sekvensdekning ved eksomsekvensering. Dette skyldes at de har stor likhet med andre områder i genomet, slik at spesifikk gjenkjennelse av disse områdene og påvisning av varianter i disse områdene, blir vanskelig og upålitelig. Disse genetiske regionene har vi identifisert ved å benytte USCS segmental duplication hvor områder større enn 1 kb og ≥90% likhet med andre regioner i genomet, gjenkjennes (https://genome.ucsc.edu). Vi gjør oppmerksom på at ved identifiseringav ekson oppstrøms for startkodon kan eksonnummereringen endres uten at transkript ID endres. Avdelingens websider har en full oversikt over områder som er affisert av segmentale duplikasjoner. ** Transkriptets kodende ekson. Ekson Gen Gen affisert (HGNC (HGNC Transkript Ekson** Fenotype av symbol) ID) segdup* ACVRL1 175 NM_000020.3 2-10 Telangiectasia, hereditary hemorrhagic, type 2 OMIM ADAMTS3 219 NM_014243.3 1-22 Hennekam lymphangiectasia- lymphedema syndrome 3 OMIM AKT1 391 NM_005163.2 2-14 Cowden syndrome 6 OMIM Proteus syndrome, somatic OMIM AKT2 392 NM_001626.6 2-14 Diabetes mellitus, type II OMIM Hypoinsulinemic hypoglycemia with hemihypertrophy OMIM AKT3 393 NM_005465.7 2-14 Megalencephaly-polymicrogyria- polydactyly-hydrocephalus syndrome 2 OMIM file:///data/SegOv_v02-web.html 1/7 2/1/2021 Segmental overvekst og vaskulærmalformasjoner v02 Ekson Gen Gen affisert (HGNC (HGNC
    [Show full text]
  • Phenotypic and Genotypic Characterisation of Noonan-Like
    1of5 ELECTRONIC LETTER J Med Genet: first published as 10.1136/jmg.2004.024091 on 2 February 2005. Downloaded from Phenotypic and genotypic characterisation of Noonan-like/ multiple giant cell lesion syndrome J S Lee, M Tartaglia, B D Gelb, K Fridrich, S Sachs, C A Stratakis, M Muenke, P G Robey, M T Collins, A Slavotinek ............................................................................................................................... J Med Genet 2005;42:e11 (http://www.jmedgenet.com/cgi/content/full/42/2/e11). doi: 10.1136/jmg.2004.024091 oonan-like/multiple giant cell lesion syndrome (NL/ MGCLS; OMIM 163955) is a rare condition1–3 with Key points Nphenotypic overlap with Noonan’s syndrome (OMIM 163950) and cherubism (OMIM 118400) (table 1). N Noonan-like/multiple giant cell lesion syndrome (NL/ Recently, missense mutations in the PTPN11 gene on MGCLS) has clinical similarities with Noonan’s syn- chromosome 12q24.1 have been identified as the cause of drome and cherubism. It is unclear whether it is a Noonan’s syndrome in 45% of familial and sporadic cases,45 distinct entity or a variant of Noonan’s syndrome or indicating genetic heterogeneity within the syndrome. In the cherubism. 5 study by Tartaglia et al, there was a family in which three N Three unrelated patients with NL/MGCLS were char- members had features of Noonan’s syndrome; two of these acterised, two of whom were found to have mutations had incidental mandibular giant cell lesions.3 All three in the PTPN11 gene, the mutation found in 45% of members were found to have a PTPN11 mutation known to patients with Noonan’s syndrome.
    [Show full text]
  • Megalencephaly and Macrocephaly
    277 Megalencephaly and Macrocephaly KellenD.Winden,MD,PhD1 Christopher J. Yuskaitis, MD, PhD1 Annapurna Poduri, MD, MPH2 1 Department of Neurology, Boston Children’s Hospital, Boston, Address for correspondence Annapurna Poduri, Epilepsy Genetics Massachusetts Program, Division of Epilepsy and Clinical Electrophysiology, 2 Epilepsy Genetics Program, Division of Epilepsy and Clinical Department of Neurology, Fegan 9, Boston Children’s Hospital, 300 Electrophysiology, Department of Neurology, Boston Children’s Longwood Avenue, Boston, MA 02115 Hospital, Boston, Massachusetts (e-mail: [email protected]). Semin Neurol 2015;35:277–287. Abstract Megalencephaly is a developmental disorder characterized by brain overgrowth secondary to increased size and/or numbers of neurons and glia. These disorders can be divided into metabolic and developmental categories based on their molecular etiologies. Metabolic megalencephalies are mostly caused by genetic defects in cellular metabolism, whereas developmental megalencephalies have recently been shown to be caused by alterations in signaling pathways that regulate neuronal replication, growth, and migration. These disorders often lead to epilepsy, developmental disabilities, and Keywords behavioral problems; specific disorders have associations with overgrowth or abnor- ► megalencephaly malities in other tissues. The molecular underpinnings of many of these disorders are ► hemimegalencephaly now understood, providing insight into how dysregulation of critical pathways leads to ►
    [Show full text]
  • Loss-Of-Function Mutation in the Prokineticin 2 Gene Causes
    Loss-of-function mutation in the prokineticin 2 gene SEE COMMENTARY causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism Nelly Pitteloud*†, Chengkang Zhang‡, Duarte Pignatelli§, Jia-Da Li‡, Taneli Raivio*, Lindsay W. Cole*, Lacey Plummer*, Elka E. Jacobson-Dickman*, Pamela L. Mellon¶, Qun-Yong Zhou‡, and William F. Crowley, Jr.* *Reproductive Endocrine Unit, Department of Medicine and Harvard Reproductive Endocrine Science Centers, Massachusetts General Hospital, Boston, MA 02114; ‡Department of Pharmacology, University of California, Irvine, CA 92697; §Department of Endocrinology, Laboratory of Cellular and Molecular Biology, Institute of Molecular Pathology and Immunology, University of Porto, San Joa˜o Hospital, 4200-465 Porto, Portugal; and ¶Departments of Reproductive Medicine and Neurosciences, University of California at San Diego, La Jolla, CA 92093 Communicated by Patricia K. Donahoe, Massachusetts General Hospital, Boston, MA, August 14, 2007 (received for review May 8, 2007) Gonadotropin-releasing hormone (GnRH) deficiency in the human associated with KS, although no functional data on the mutant presents either as normosmic idiopathic hypogonadotropic hypo- proteins were provided (17). Herein, we demonstrate that homozy- gonadism (nIHH) or with anosmia [Kallmann syndrome (KS)]. To gous loss-of-function mutations in the PROK2 gene cause IHH in date, several loci have been identified to cause these disorders, but mice and humans. only 30% of cases exhibit mutations in known genes. Recently, murine studies have demonstrated a critical role of the prokineticin Results pathway in olfactory bulb morphogenesis and GnRH secretion. Molecular Analysis of PROK2 Gene. A homozygous single base pair Therefore, we hypothesize that mutations in prokineticin 2 deletion in exon 2 of the PROK2 gene (c.[163delA]ϩ [163delA]) (PROK2) underlie some cases of KS in humans and that animals was identified in the proband, in his brother with KS, and in his deficient in Prok2 would be hypogonadotropic.
    [Show full text]
  • Kallmann Syndrome
    Kallmann syndrome Author: DoctorJean-Pierre Hardelin1 Creation date: July 1997 Updates: May 2002 December 2003 February 2005 Scientific editor: Professor Philippe Bouchard 1 Unité de Génétique des Déficits Sensoriels (INSERM U587), Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France. [email protected] Abstract Keywords Disease name and synonyms Excluded diseases Diagnostic criteria / Definition Differential diagnosis Incidence Clinical description Management including treatment Etiology Diagnostic methods Genetic counseling Prenatal diagnosis Unresolved questions and comments References Abstract Kallmann syndrome combines hypogonadotropic hypogonadism due to GnRH deficiency, with anosmia or hyposmia. Magnetic resonance imaging (MRI) shows hypoplasia or aplasia of the olfactory bulbs. The incidence is estimated at 1 case in 10,000 males and 1 case in 50,000 females. The main clinical features consist of the association of micropenis and cryptorchidism in young boys, the absence of spontaneous puberty, a partial or total loss of the sense of smell (anosmia). Other possible signs include mirror movements of the upper limbs (synkinesis), unilateral or bilateral renal aplasia, cleft lip/palate, dental agenesis, arched feet, deafness. Diagnostic methods consist of hormones evaluation (GnRH stimulation test) as well as qualitative and quantitative olfactometric evaluation. Hormonal replacement is used to induce puberty, and later, fertility. Kallmann syndrome is due to an impaired embryonic development of the olfactory system and the GnRH-synthesizing neurons. Sporadic cases have been predominantly reported. Three modes of inheritance have been described in familial forms: X-linked recessive, autosomal dominant, or more rarely autosomal recessive. To date, only two of the genes responsible for this genetically heterogeneous disease have been identified: KAL-1, responsible for the X-linked form and FGFR1, involved in the autosomal dominant form (KAL-2).
    [Show full text]
  • Gonadotropin-Releasing Hormone Agonist Treatment of Girls with Constitutional Short Stature and Normal Pubertal Development
    0021-972X/96/$03.00/0 Vol. 81, No. 9 Journal of Clmcal Endocrinology and Metabolism Printed in U.S.A. Copyright 0 1996 by The Endocrine Society Gonadotropin-Releasing Hormone Agonist Treatment of Girls with Constitutional Short Stature and Normal Pubertal Development JEAN-CLAUDE CAREL, FRlkDliRIQUE HAY, RliGIS COUTANT, DANIlkLE RODRIGUE, AND JEAN-LOUIS CHAUSSAIN Downloaded from https://academic.oup.com/jcem/article/81/9/3318/2651102 by guest on 23 September 2021 INSERM U-342 and Department of Pediatric Endocrinology, University of Paris V, Hbpital Saint Vincent de Paul, Paris, France ABSTRACT interruption of treatment, bone age was 14.9 2 1.3 yr (~13.5 yr in all GnRH agonists have been proposed to improve final height in patients), height was 149.1 k 4 cm, and final height prognosis was patients with constitutional short stature. We treated 31 girls, aged 150.6 2 3.6 cm. Final height prognosis was 1 2 2.3 cm greater than 11.9 i 1 yr (mean t- SD), with short stature, recent pubertal onset and pretreatment height prognosis (P < 0.02) and 1.2 k 2.2 cm below the predicted final height of 155 cm or less with depot triptorelin. During height predicted at the end of the treatment (P < 0.01). No major the 23 2 4 months of treatment, bone age progression was 0.6 ? 0.3 side-effect was observed. Height SD score decreased during treatment bone age yr/yr, and growth velocity declined from 7 k 2 to 4 2 0.8 with GnRH agonist from -2.3 ? 0.9 to -2.7 -C 0.7 SD score (P < cm/yr (P < 0.0001).
    [Show full text]
  • Cardiomyopathy Precision Panel Overview Indications
    Cardiomyopathy Precision Panel Overview Cardiomyopathies are a group of conditions with a strong genetic background that structurally hinder the heart to pump out blood to the rest of the body due to weakness in the heart muscles. These diseases affect individuals of all ages and can lead to heart failure and sudden cardiac death. If there is a family history of cardiomyopathy it is strongly recommended to undergo genetic testing to be aware of the family risk, personal risk, and treatment options. Most types of cardiomyopathies are inherited in a dominant manner, which means that one altered copy of the gene is enough for the disease to present in an individual. The symptoms of cardiomyopathy are variable, and these diseases can present in different ways. There are 5 types of cardiomyopathies, the most common being hypertrophic cardiomyopathy: 1. Hypertrophic cardiomyopathy (HCM) 2. Dilated cardiomyopathy (DCM) 3. Restrictive cardiomyopathy (RCM) 4. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) 5. Isolated Left Ventricular Non-Compaction Cardiomyopathy (LVNC). The Igenomix Cardiomyopathy Precision Panel serves as a diagnostic and tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes. Indications The Igenomix Cardiomyopathy Precision Panel is indicated in those cases where there is a clinical suspicion of cardiomyopathy with or without the following manifestations: - Shortness of breath - Fatigue - Arrythmia (abnormal heart rhythm) - Family history of arrhythmia - Abnormal scans - Ventricular tachycardia - Ventricular fibrillation - Chest Pain - Dizziness - Sudden cardiac death in the family 1 Clinical Utility The clinical utility of this panel is: - The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history of cardiomyopathy, channelopathy or sudden cardiac death.
    [Show full text]
  • Dental-Craniofacial Manifestation and Treatment of Rare Diseases
    International Journal of Oral Science www.nature.com/ijos REVIEW ARTICLE OPEN Dental-craniofacial manifestation and treatment of rare diseases En Luo1, Hanghang Liu1, Qiucheng Zhao1, Bing Shi1 and Qianming Chen1 Rare diseases are usually genetic, chronic and incurable disorders with a relatively low incidence. Developments in the diagnosis and management of rare diseases have been relatively slow due to a lack of sufficient profit motivation and market to attract research by companies. However, due to the attention of government and society as well as economic development, rare diseases have been gradually become an increasing concern. As several dental-craniofacial manifestations are associated with rare diseases, we summarize them in this study to help dentists and oral maxillofacial surgeons provide an early diagnosis and subsequent management for patients with these rare diseases. International Journal of Oral Science (2019) 11:9 ; https://doi.org/10.1038/s41368-018-0041-y INTRODUCTION In this review, we aim to summarize the related manifestations Recently, the National Health and Health Committee of China first and treatment of dental-craniofacial disorders related to rare defined 121 rare diseases in the Chinese population. The list of diseases, thus helping to improve understanding and certainly these rare diseases was established according to prevalence, diagnostic capacity for dentists and oral maxillofacial surgeons. disease burden and social support, medical technology status, and the definition of rare diseases in relevant international institutions. Twenty million people in China were reported to suffer from these DENTAL-CRANIOFACIAL DISORDER-RELATED RARE DISEASES rare diseases. Tooth dysplasia A rare disease is any disease or condition that affects a small Congenital ectodermal dysplasia.
    [Show full text]
  • MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature
    J M Wit and others Genetics of short stature 174:4 R145–R173 Review MECHANISMS IN ENDOCRINOLOGY Novel genetic causes of short stature 1 1 2 2 Jan M Wit , Wilma Oostdijk , Monique Losekoot , Hermine A van Duyvenvoorde , Correspondence Claudia A L Ruivenkamp2 and Sarina G Kant2 should be addressed to J M Wit Departments of 1Paediatrics and 2Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Email The Netherlands [email protected] Abstract The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature.
    [Show full text]
  • Fetal Hydrops in Combination with Gonadoblastoid Testicular Dysplasia May Represent a Lethal Type of Noonan Syndrome
    etics & E en m G b ry n o a l o Reischer et al., Human Genet Embryol 2016, 6:3 m g u y H Human Genetics & Embryology DOI: 10.4172/2161-0436.1000137 ISSN: 2161-0436 Research Article Open Access Fetal Hydrops in Combination with Gonadoblastoid Testicular Dysplasia May Represent a Lethal Type of Noonan Syndrome Theresa Reischer1, Maximilian Schmid1, Sukirthini Balendran1, Manuel Nistal2, Julia Vodopiutz3, Elisabeth Krampl-Bettelheim4, Niko Popitsch5, Sandra Liebmann-Reindl6 and Berthold Streubel6,7* 1Department of Obstetrics and Feto-Maternal Medicine, Medical University of Vienna, Vienna, Austria 2Department of Pathology, Hospital La Paz, Universidad Autónoma de Madrid, Spain 3Department of Pediatrics, Medical University of Vienna, Vienna, Austria 4Fetomed - Center for Fetal Medicine, Doebling Private Hospital, Vienna, Austria 5Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK 6Core Facility Genomics, Medical University of Vienna, Vienna, Austria 7Department of Pathology, Medical University of Vienna, Austria Abstract Objectives: Fetal gonadoblastoid testicular dysplasia is a rare finding. The combination with typical features of Noonan syndrome has never been described so far. We performed genetic testing including whole exome sequencing in two cases with fetal hydrops, congenital heart disease and gonadoblastoid testicular dysplasia. Methods: Exome sequencing was performed in the index case, where high quality DNA was isolated from fetal blood. In the second case and in five further gonadoblastoma samples, conventional Sanger sequencing was performed on DNA isolated from formalin fixed, paraffin embedded tissue. Results: Whole exome sequencing of the index case revealed a pathogenic mutation in the RIT1 gene (c.270G>A (p.Met90Ile)), leading to the diagnosis of Noonan syndrome type 8.
    [Show full text]
  • Case Report Kallmann's Syndrome: Clues to Clinical Diagnosis
    International Journal of Impotence Research (2000) 12, 121±123 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir Case Report Kallmann's Syndrome: clues to clinical diagnosis H John1* and C Schmid2 Departments of 1Urology and 2Medicine (Division of Endocrinology), ZuÈrich University Hospital, Switzerland Hypogonadotropic patients may visit pediatricians, general practitioners, endocrinologists or urologists, presenting with microphallus, cryptochidism or pubertas tarda and delayed bone maturation. Congenital hypogonadotropic hypogonadism is characterized, apart from small testes, by the constellation of low serum levels of testosterone, LH and FSH. Kallman's syndrome is characterized by congenital hypogonadotropic hypogonadism with midline defects such as anosmia (a de®ciency of the sense of smell).1 The ®rst case report dates back to 1856,2 and genetic defects causing the syndrome have been recently described.3 The diagnosis can be clinically suspected and is established by con®rming hormonal studies. International Journal of Impotence Research (2000) 12, 121±123. Case Reports Case 2 Case 1 A 24-year-old patient consulted a general practi- tioner (the ®rst to address the problem of delayed puberty) for upper airway disease. He presented A 26-year old man fell on his right hand. The X-ray with an unbroken voice and sparse axillary and of the wrist (Figure 1) not only demonstrated the pubic body hair. He had a microphallus and fracture of the ®fth metacarpus but also an open testicular volumes of 2 ml, and a bone age of 17 epiphyseal line, thus revealing markedly delayed years. He did not smell garlic or curry.
    [Show full text]