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Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome(ISQMR)

MedGen UID:
482486
Concept ID:
C3280856
Disease or Syndrome
Synonyms: ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND IMPAIRED INTELLECTUAL DEVELOPMENT; Ichthyosis, spastic quadriplegia, and mental retardation; ISQMR
SNOMED CT: ELOVL4 (elongation of very long chain fatty acids-like 4) related neuro ichthyosis (1208936008); Congenital ichthyosis, intellectual disability, spastic quadriplegia syndrome (1208936008); ELOVL4-related neuro ichthyosis (1208936008)
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).
 
Gene (location): ELOVL4 (6q14.1)
 
Monarch Initiative: MONDO:0013760
OMIM®: 614457
Orphanet: ORPHA352333

Definition

ISQMR is a severe autosomal recessive disorder characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures (summary by Aldahmesh et al., 2011). [from OMIM]

Clinical features

From HPO
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
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.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Abnormality of visual evoked potentials
MedGen UID:
105509
Concept ID:
C0522214
Finding
An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Generalized myoclonic seizure
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Aplasia/Hypoplasia involving the central nervous system
MedGen UID:
871188
Concept ID:
C4025665
Finding
Absence or underdevelopment of tissue in the central nervous system.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Joint contracture
MedGen UID:
3228
Concept ID:
C0009918
Anatomical Abnormality
A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.
Congenital nonbullous ichthyosiform erythroderma
MedGen UID:
38180
Concept ID:
C0079154
Disease or Syndrome
The term collodion baby applies to newborns who appear to have an extra layer of skin (known as a collodion membrane) that has a collodion-like quality. It is a descriptive term, not a specific diagnosis or disorder (as such, it is a syndrome). Affected babies are born in a collodion membrane, a shiny waxy outer layer to the skin. This is shed 10-14 days after birth, revealing the main symptom of the disease, extensive scaling of the skin caused by hyperkeratosis. With increasing age, the scaling tends to be concentrated around joints in areas such as the groin, the armpits, the inside of the elbow and the neck. The scales often tile the skin and may resemble fish scales.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Scaling skin
MedGen UID:
472970
Concept ID:
C0237849
Finding
Refers to the loss of the outer layer of the epidermis in large, scale-like flakes.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital ichthyosis-intellectual disability-spastic quadriplegia syndrome
Follow this link to review classifications for Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome in Orphanet.

Professional guidelines

PubMed

Almannai M, Marafi D, Abdel-Salam GMH, Zaki MS, Duan R, Calame D, Herman I, Levesque F, Elbendary HM, Hegazy I, Chung WK, Kavus H, Saeidi K, Maroofian R, AlHashim A, Al-Otaibi A, Al Madhi A, Abou Al-Seood HM, Alasmari A, Houlden H, Gleeson JG, Hunter JV, Posey JE, Lupski JR, El-Hattab AW
Clin Genet 2022 May;101(5-6):530-540. Epub 2022 Apr 12 doi: 10.1111/cge.14132. PMID: 35322404Free PMC Article
Pang D, Nemzek WR, Zovickian J
Neurosurgery 2007 Nov;61(5):995-1015; discussion 1015. doi: 10.1227/01.neu.0000303196.87672.78. PMID: 18091277

Recent clinical studies

Etiology

Wang C, He G, Ge Y, Li R, Li Z, Lin Y
Mol Genet Genomic Med 2020 Jun;8(6):e1235. Epub 2020 Apr 7 doi: 10.1002/mgg3.1235. PMID: 32255274Free PMC Article
Abdollahpour H, Alawi M, Kortüm F, Beckstette M, Seemanova E, Komárek V, Rosenberger G, Kutsche K
Eur J Hum Genet 2015 Feb;23(2):256-9. Epub 2014 Apr 30 doi: 10.1038/ejhg.2014.73. PMID: 24781758Free PMC Article
Lamari F, Mochel F, Sedel F, Saudubray JM
J Inherit Metab Dis 2013 May;36(3):411-25. Epub 2012 Jul 20 doi: 10.1007/s10545-012-9509-7. PMID: 22814679
Kurosawa K, Enomoto K, Tominaga M, Furuya N, Sameshima K, Iai M, Take H, Shinkai M, Ishikawa H, Yamanaka M, Matsui K, Masuno M
Congenit Anom (Kyoto) 2012 Jun;52(2):78-81. doi: 10.1111/j.1741-4520.2012.00357.x. PMID: 22639992
Clark M, Carr L, Reilly S, Neville BG
Brain 2000 Oct;123 ( Pt 10):2160-70. doi: 10.1093/brain/123.10.2160. PMID: 11004132

Diagnosis

Tavares JS, Gama GL, Dias Borges MC, de Sousa Santos AC, Tavares JS, Amorim MMR, Melo A
Dev Neurorehabil 2021 Jul;24(5):296-302. Epub 2021 Jan 3 doi: 10.1080/17518423.2020.1866706. PMID: 33393410
Abdollahpour H, Alawi M, Kortüm F, Beckstette M, Seemanova E, Komárek V, Rosenberger G, Kutsche K
Eur J Hum Genet 2015 Feb;23(2):256-9. Epub 2014 Apr 30 doi: 10.1038/ejhg.2014.73. PMID: 24781758Free PMC Article
Lamari F, Mochel F, Sedel F, Saudubray JM
J Inherit Metab Dis 2013 May;36(3):411-25. Epub 2012 Jul 20 doi: 10.1007/s10545-012-9509-7. PMID: 22814679
Kurosawa K, Enomoto K, Tominaga M, Furuya N, Sameshima K, Iai M, Take H, Shinkai M, Ishikawa H, Yamanaka M, Matsui K, Masuno M
Congenit Anom (Kyoto) 2012 Jun;52(2):78-81. doi: 10.1111/j.1741-4520.2012.00357.x. PMID: 22639992
Clark M, Neville BG
Am J Med Genet A 2008 Jan 1;146A(1):35-42. doi: 10.1002/ajmg.a.32015. PMID: 17994559

Therapy

Molinelli A, Cozzani E, Burlando M, Santi P, Parodi A, Ventura F
G Ital Dermatol Venereol 2020 Dec;155(6):780-782. doi: 10.23736/S0392-0488.16.05231-7. PMID: 33645938
Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450
Broomall E, McBride ME, Deal BJ, Ducharme-Crevier L, Shaw A, Mazwi M, Backer CL, Mongé MC, Costello J, Marino BS, DeFreitas A, Wainwright MS
Ann Thorac Surg 2016 Jun;101(6):2315-20. Epub 2016 Mar 24 doi: 10.1016/j.athoracsur.2016.01.001. PMID: 27016841
Samartzis D, Shen FH, Herman J, Mardjetko SM
Spine (Phila Pa 1976) 2010 Feb 15;35(4):E119-27. doi: 10.1097/BRS.0b013e3181c9f957. PMID: 20160615
Margari L, Presicci A, Ventura P, Buttiglione M, Andreula C, Perniola T
Brain Dev 2005 Jan;27(1):53-7. doi: 10.1016/j.braindev.2004.03.006. PMID: 15626542

Prognosis

Wang C, He G, Ge Y, Li R, Li Z, Lin Y
Mol Genet Genomic Med 2020 Jun;8(6):e1235. Epub 2020 Apr 7 doi: 10.1002/mgg3.1235. PMID: 32255274Free PMC Article
Lansdon LA, Bernabe HV, Nidey N, Standley J, Schnieders MJ, Murray JC
J Dent Res 2017 Oct;96(11):1339-1345. Epub 2017 Aug 21 doi: 10.1177/0022034517726496. PMID: 28825856Free PMC Article
Lee HJ, Cho DY
Pediatr Neurosurg 2001 Oct;35(4):181-7. doi: 10.1159/000050419. PMID: 11694795
Clark M, Carr L, Reilly S, Neville BG
Brain 2000 Oct;123 ( Pt 10):2160-70. doi: 10.1093/brain/123.10.2160. PMID: 11004132
Jagell S, Heijbel J
Helv Paediatr Acta 1982;37(6):519-30. PMID: 7166487

Clinical prediction guides

Almannai M, Marafi D, Abdel-Salam GMH, Zaki MS, Duan R, Calame D, Herman I, Levesque F, Elbendary HM, Hegazy I, Chung WK, Kavus H, Saeidi K, Maroofian R, AlHashim A, Al-Otaibi A, Al Madhi A, Abou Al-Seood HM, Alasmari A, Houlden H, Gleeson JG, Hunter JV, Posey JE, Lupski JR, El-Hattab AW
Clin Genet 2022 May;101(5-6):530-540. Epub 2022 Apr 12 doi: 10.1111/cge.14132. PMID: 35322404Free PMC Article
Tavares JS, Gama GL, Dias Borges MC, de Sousa Santos AC, Tavares JS, Amorim MMR, Melo A
Dev Neurorehabil 2021 Jul;24(5):296-302. Epub 2021 Jan 3 doi: 10.1080/17518423.2020.1866706. PMID: 33393410
Wang C, He G, Ge Y, Li R, Li Z, Lin Y
Mol Genet Genomic Med 2020 Jun;8(6):e1235. Epub 2020 Apr 7 doi: 10.1002/mgg3.1235. PMID: 32255274Free PMC Article
Hozhabri H, Talebi M, Mehrjardi MYV, De Luca A, Dehghani M
Am J Med Genet A 2020 May;182(5):957-961. Epub 2020 Mar 12 doi: 10.1002/ajmg.a.61543. PMID: 32162791
Kurosawa K, Enomoto K, Tominaga M, Furuya N, Sameshima K, Iai M, Take H, Shinkai M, Ishikawa H, Yamanaka M, Matsui K, Masuno M
Congenit Anom (Kyoto) 2012 Jun;52(2):78-81. doi: 10.1111/j.1741-4520.2012.00357.x. PMID: 22639992

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