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Epilepsy-microcephaly-skeletal dysplasia syndrome

MedGen UID:
330468
Concept ID:
C1832437
Disease or Syndrome
Synonym: Mental Retardation, Microcephaly, Epilepsy, And Coarse Face
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0011048
OMIM®: 601352
Orphanet: ORPHA1948

Definition

A rare multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, hypotonia, seizures, microcephaly, delayed bone maturation, and skeletal abnormalities (such as scoliosis or pectus excavatum, among others). Dysmorphic features include coarse face, hirsutism, thick eyebrows, broad nasal septum, short philtrum, large mouth, and prominent ears. There have been no further descriptions in the literature since 1996. [from ORDO]

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEpilepsy-microcephaly-skeletal dysplasia syndrome
Follow this link to review classifications for Epilepsy-microcephaly-skeletal dysplasia syndrome in Orphanet.

Professional guidelines

PubMed

Garcia-Manero G
Am J Hematol 2023 Aug;98(8):1307-1325. Epub 2023 Jun 8 doi: 10.1002/ajh.26984. PMID: 37288607
Sekeres MA, Taylor J
JAMA 2022 Sep 6;328(9):872-880. doi: 10.1001/jama.2022.14578. PMID: 36066514
Patnaik MM, Tefferi A
Am J Hematol 2022 Mar 1;97(3):352-372. Epub 2022 Jan 27 doi: 10.1002/ajh.26455. PMID: 34985762

Recent clinical studies

Etiology

Wright JT, Fete M, Schneider H, Zinser M, Koster MI, Clarke AJ, Hadj-Rabia S, Tadini G, Pagnan N, Visinoni AF, Bergendal B, Abbott B, Fete T, Stanford C, Butcher C, D'Souza RN, Sybert VP, Morasso MI
Am J Med Genet A 2019 Mar;179(3):442-447. Epub 2019 Jan 31 doi: 10.1002/ajmg.a.61045. PMID: 30703280Free PMC Article
Grunauer M, Jorge AAL
Growth Horm IGF Res 2018 Feb;38:29-33. Epub 2017 Dec 6 doi: 10.1016/j.ghir.2017.12.003. PMID: 29249624
Peco-Antić A
Med Pregl 2007;60 Suppl 2:48-52. PMID: 18928157
Itin PH, Fistarol SK
Am J Med Genet C Semin Med Genet 2004 Nov 15;131C(1):45-51. doi: 10.1002/ajmg.c.30033. PMID: 15468153
Spranger JW
Postgrad Med J 1977 Aug;53(622):480-7. doi: 10.1136/pgmj.53.622.480. PMID: 335375Free PMC Article

Diagnosis

Berberian JG
Emerg Med Clin North Am 2022 Nov;40(4):651-662. Epub 2022 Oct 7 doi: 10.1016/j.emc.2022.06.005. PMID: 36396213
Sataite I, Cudlip S, Jayamohan J, Ganau M
Handb Clin Neurol 2021;181:51-64. doi: 10.1016/B978-0-12-820683-6.00005-1. PMID: 34238479
Vanlerberghe C, Boutry N, Petit F
Clin Genet 2018 Jul;94(1):43-53. Epub 2018 Apr 11 doi: 10.1111/cge.13209. PMID: 29322497
Lubinsky M, Kantaputra PN
Am J Med Genet A 2016 Oct;170(10):2611-6. Epub 2016 Jun 2 doi: 10.1002/ajmg.a.37763. PMID: 27250821
Spranger JW
Postgrad Med J 1977 Aug;53(622):480-7. doi: 10.1136/pgmj.53.622.480. PMID: 335375Free PMC Article

Therapy

Garcia-Manero G
Am J Hematol 2023 Aug;98(8):1307-1325. Epub 2023 Jun 8 doi: 10.1002/ajh.26984. PMID: 37288607
Lee P, Yim R, Yung Y, Chu HT, Yip PK, Gill H
Int J Mol Sci 2021 Sep 23;22(19) doi: 10.3390/ijms221910232. PMID: 34638574Free PMC Article
Miao L, Zhang Z, Ren Z, Li Y
Front Immunol 2021;12:663201. Epub 2021 Apr 28 doi: 10.3389/fimmu.2021.663201. PMID: 33995389Free PMC Article
Behnke J, Lemyre B, Czernik C, Zimmer KP, Ehrhardt H, Waitz M
Dtsch Arztebl Int 2019 Mar 8;116(11):177-183. doi: 10.3238/arztebl.2019.0177. PMID: 31014448Free PMC Article
Tanaka TN, Bejar R
Blood 2019 Mar 7;133(10):1086-1095. Epub 2019 Jan 22 doi: 10.1182/blood-2018-10-844670. PMID: 30670443

Prognosis

Wang X, Li Y, Shi T, Bont LJ, Chu HY, Zar HJ, Wahi-Singh B, Ma Y, Cong B, Sharland E, Riley RD, Deng J, Figueras-Aloy J, Heikkinen T, Jones MH, Liese JG, Markić J, Mejias A, Nunes MC, Resch B, Satav A, Yeo KT, Simões EAF, Nair H; Respiratory Virus Global Epidemiology Network; RESCEU investigators
Lancet 2024 Mar 30;403(10433):1241-1253. Epub 2024 Feb 14 doi: 10.1016/S0140-6736(24)00138-7. PMID: 38367641
Siddique AW, Ahmed Z, Haider A, Khalid H, Karim T
J Ayub Med Coll Abbottabad 2019 Apr-Jun;31(2):290-292. PMID: 31094135
Grignano E, Jachiet V, Fenaux P, Ades L, Fain O, Mekinian A
Ann Hematol 2018 Nov;97(11):2015-2023. Epub 2018 Aug 8 doi: 10.1007/s00277-018-3472-9. PMID: 30091023
Abboud JA, Bateman DK, Barlow J
J Am Acad Orthop Surg 2016 May;24(5):327-36. doi: 10.5435/JAAOS-D-15-00032. PMID: 27055054
Bhatia S, Holla RG
Indian Pediatr 2005 Apr;42(4):373-5. PMID: 15876600

Clinical prediction guides

Raimondi F, Migliaro F, Corsini I, Meneghin F, Dolce P, Pierri L, Perri A, Aversa S, Nobile S, Lama S, Varano S, Savoia M, Gatto S, Leonardi V, Capasso L, Carnielli VP, Mosca F, Dani C, Vento G, Lista G
Pediatrics 2021 Apr;147(4) Epub 2021 Mar 9 doi: 10.1542/peds.2020-030528. PMID: 33688032
Rudnicka L, Olszewska M, Waśkiel A, Rakowska A
Dermatol Clin 2018 Oct;36(4):421-430. Epub 2018 Aug 16 doi: 10.1016/j.det.2018.05.009. PMID: 30201151
Vanlerberghe C, Boutry N, Petit F
Clin Genet 2018 Jul;94(1):43-53. Epub 2018 Apr 11 doi: 10.1111/cge.13209. PMID: 29322497
Geister KA, Camper SA
Annu Rev Genomics Hum Genet 2015;16:199-227. Epub 2015 Apr 22 doi: 10.1146/annurev-genom-090314-045904. PMID: 25939055Free PMC Article
Huber C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):165-74. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31336. PMID: 22791528

Recent systematic reviews

Silveira RC, Panceri C, Munõz NP, Carvalho MB, Fraga AC, Procianoy RS
J Pediatr (Rio J) 2024 Jan-Feb;100(1):8-24. Epub 2023 Jun 21 doi: 10.1016/j.jped.2023.05.008. PMID: 37353207Free PMC Article
Cerezo-Cayuelas M, Pérez-Silva A, Serna-Muñoz C, Vicente A, Martínez-Beneyto Y, Cabello-Malagón I, Ortiz-Ruiz AJ
Orphanet J Rare Dis 2022 Oct 17;17(1):376. doi: 10.1186/s13023-022-02533-0. PMID: 36253866Free PMC Article
Le Berre C, Peyrin-Biroulet L; SPIRIT-IOIBD study group
Gastroenterology 2021 Apr;160(5):1452-1460.e21. Epub 2021 Jan 6 doi: 10.1053/j.gastro.2020.10.065. PMID: 33421515
West S, Nevitt SJ, Cotton J, Gandhi S, Weston J, Sudan A, Ramirez R, Newton R
Cochrane Database Syst Rev 2019 Jun 25;6(6):CD010541. doi: 10.1002/14651858.CD010541.pub3. PMID: 31237346Free PMC Article
van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, Kuis W, Schulpen TW, L'Hoir MP
Pediatrics 2007 Oct;120(4):e1097-106. doi: 10.1542/peds.2006-2083. PMID: 17908730

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