U.S. flag

An official website of the United States government


Send to:

Choose Destination

Ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: Ectodermal dysplasia, hypohidrotic, with hypothyroidism and agenesis of the corpus callosum
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
Concept ID:
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Monarch Initiative: MONDO:0009149
OMIM®: 225040
Orphanet: ORPHA1812


Ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome is a rare, multiple developmental anomalies syndrome characterized by the triad of ectodermal dysplasia (mostly hypohidrotic with dry skin and reduced sweating and sparse, fair scalp hair, eyebrows and eyelashes), severe intellectual disability and variable central nervous system anomalies (cerebellar hypoplasia, dilatation of ventricles, corpus callosum agenesis, Dandy-Walker malformation). Distinct craniofacial dysmorphism with macrocephaly, frontal bossing, midfacial hypoplasia and high arched or cleft palate, as well as cryptorchidism, feeding difficulties and hypotonia, are associated. There have been no further descriptions in the literature since 1998. [from ORDO]

Clinical features

From HPO
Intellectual disability, severe
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Corpus callosum, agenesis of
MedGen UID:
Concept ID:
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Intellectual disability, progressive
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Abnormality of the skeletal system
MedGen UID:
Concept ID:
Anatomical Abnormality
An abnormality of the skeletal system.
Abnormality of metabolism/homeostasis
MedGen UID:
Concept ID:
Hypohidrotic ectodermal dysplasia
MedGen UID:
Concept ID:
Disease or Syndrome
Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). The cardinal features of classic HED become obvious during childhood. The scalp hair is thin, lightly pigmented, and slow growing. Sweating, although present, is greatly deficient, leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature. Only a few abnormally formed teeth erupt, at a later-than-average age. Physical growth and psychomotor development are otherwise within normal limits. Mild HED is characterized by mild manifestations of any or all the characteristic features.
MedGen UID:
Concept ID:
Disease or Syndrome
An enlargement of the thyroid gland.
Primary hypothyroidism
MedGen UID:
Concept ID:
Disease or Syndrome
A type of hypothyroidism that results from a defect in the thyroid gland.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEctodermal dysplasia-intellectual disability-central nervous system malformation syndrome
Follow this link to review classifications for Ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome in Orphanet.

Recent clinical studies


Samara A, Gusman M, Aker L, Parsons MS, Mian AY, Eldaya RW
Curr Probl Diagn Radiol 2022 Sep-Oct;51(5):747-758. Epub 2021 Aug 28 doi: 10.1067/j.cpradiol.2021.07.002. PMID: 34607749
Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C
Childs Nerv Syst 2020 Oct;36(10):2229-2268. Epub 2020 Sep 17 doi: 10.1007/s00381-020-04758-5. PMID: 32940773
Blount JP, George TM, Koueik J, Iskandar BJ
Birth Defects Res 2019 Nov 15;111(19):1564-1576. Epub 2019 Oct 2 doi: 10.1002/bdr2.1588. PMID: 31576681
Lara-Reyna J, Carlton J, Parker WE, Greenfield JP
Childs Nerv Syst 2018 Dec;34(12):2353-2359. Epub 2018 Aug 21 doi: 10.1007/s00381-018-3950-3. PMID: 30128838
Owen LG, Hanno R
Cutis 1978 Jun;21(6):848-51. PMID: 95921


Carey JC, Opitz JM
Am J Med Genet A 2023 Feb;191(2):640-646. Epub 2022 Nov 4 doi: 10.1002/ajmg.a.63028. PMID: 36331276
Neau JP, Godeneche G, Mathis S, Guillet G
Handb Clin Neurol 2014;121:1561-94. doi: 10.1016/B978-0-7020-4088-7.00104-8. PMID: 24365436
Bellet JS
Semin Perinatol 2013 Feb;37(1):20-5. doi: 10.1053/j.semperi.2012.11.006. PMID: 23419759
Bennàssar A, Ferrando J, Grimalt R
World J Pediatr 2011 May;7(2):111-7. Epub 2011 May 15 doi: 10.1007/s12519-011-0262-z. PMID: 21574026
Owen LG, Hanno R
Cutis 1978 Jun;21(6):848-51. PMID: 95921


Adachi T, Takigawa H, Nomura T, Watanabe Y, Kowa H
Intern Med 2018 Jan 1;57(1):97-99. Epub 2017 Oct 16 doi: 10.2169/internalmedicine.9052-17. PMID: 29033429Free PMC Article
Cassina M, Johnson DL, Robinson LK, Braddock SR, Xu R, Jimenez JL, Mirrasoul N, Salas E, Luo YJ, Jones KL, Chambers CD; Organization of Teratology Information Specialists Collaborative Research Group
Arthritis Rheum 2012 Jul;64(7):2085-94. doi: 10.1002/art.34419. PMID: 22307734
Montalvan E, Mazzone C, Tofsky N, Mupparapu M
Pediatr Dent 2006 Jul-Aug;28(4):345-9. PMID: 16903444
Peterson RE, Theobald HM, Kimmel GL
Crit Rev Toxicol 1993;23(3):283-335. doi: 10.3109/10408449309105013. PMID: 8260069
Johnston MC, Bronsky PT
J Craniofac Genet Dev Biol 1991 Oct-Dec;11(4):277-91. PMID: 1812129


Jelin AC, Mahle A, Tran SH, Sparks TN, Rauen KA
Am J Med Genet A 2023 Feb;191(2):323-331. Epub 2022 Oct 29 doi: 10.1002/ajmg.a.63020. PMID: 36308388Free PMC Article
Dugan SL, Botto LD, Hedlund GL, Bale JF Jr
Semin Pediatr Neurol 2018 Jul;26:135-139. Epub 2017 Apr 2 doi: 10.1016/j.spen.2017.03.022. PMID: 29961505
Mumtaz S, Yıldız E, Jabeen S, Khan A, Tolun A, Malik S
Am J Med Genet A 2015 Dec;167A(12):3148-52. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37299. PMID: 26333564
Reinker KA, Stevenson DA, Tsung A
J Pediatr Orthop 2011 Jul-Aug;31(5):599-605. doi: 10.1097/BPO.0b013e318220396e. PMID: 21654472
Atar M, Körperich EJ
J Dent 2010 Apr;38(4):296-306. Epub 2010 Jan 13 doi: 10.1016/j.jdent.2009.12.001. PMID: 20004698

Clinical prediction guides

Boujtat K, Rouf S, Boutahar I, Skiker I, Tajir M, Latrech H
Pediatr Endocrinol Rev 2018 Dec;16(2):275-283. doi: 10.17458/per.vol16.2018.ellisvananddandywaler. PMID: 30556660
Mironova YA, Lin JP, Kalinski AL, Huffman LD, Lenk GM, Havton LA, Meisler MH, Giger RJ
Hum Mol Genet 2018 Jul 15;27(14):2443-2453. doi: 10.1093/hmg/ddy145. PMID: 29688489Free PMC Article
Vilain C, Mortier G, Van Vliet G, Dubourg C, Heinrichs C, de Silva D, Verloes A, Baumann C
Am J Med Genet A 2009 Jul;149A(7):1476-81. doi: 10.1002/ajmg.a.32678. PMID: 19504604
Moroni I, Bedeschi F, Luksch R, Casanova M, D'Incerti L, Uziel G, Selicorni A
Clin Dysmorphol 2000 Oct;9(4):265-8. doi: 10.1097/00019605-200009040-00006. PMID: 11045582
Peterson RE, Theobald HM, Kimmel GL
Crit Rev Toxicol 1993;23(3):283-335. doi: 10.3109/10408449309105013. PMID: 8260069

Supplemental Content

Table of contents

    Clinical resources

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...