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RIDDLE syndrome(RIDL)

MedGen UID:
394368
Concept ID:
C2677792
Disease or Syndrome
Synonyms: Radiosensitivity, Immunodeficiency, Dysmorphic Features, and Learning Difficulties; Riddle Syndrome
SNOMED CT: RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, learning difficulties) syndrome (783099001); RIDDLE syndrome (783099001); RNF168 (ring finger protein 168) deficiency (783099001); Radiosensitivity, immunodeficiency, dysmorphic features, learning difficulties syndrome (783099001)
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): RNF168 (3q29)
 
Monarch Initiative: MONDO:0012764
OMIM®: 611943
Orphanet: ORPHA420741

Definition

RIDDLE is an acronym for the major features of this syndrome: radiosensitivity, immunodeficiency, dysmorphic facies, and learning difficulties (Stewart et al., 2007). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Increased sensitivity to ionizing radiation
MedGen UID:
867472
Concept ID:
C4021850
Finding
An abnormally increased sensitivity to the effects of ionizing radiation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRIDDLE syndrome

Recent clinical studies

Etiology

Mantere T, Tervasmäki A, Nurmi A, Rapakko K, Kauppila S, Tang J, Schleutker J, Kallioniemi A, Hartikainen JM, Mannermaa A, Nieminen P, Hanhisalo R, Lehto S, Suvanto M, Grip M, Jukkola-Vuorinen A, Tengström M, Auvinen P, Kvist A, Borg Å, Blomqvist C, Aittomäki K, Greenberg RA, Winqvist R, Nevanlinna H, Pylkäs K
Sci Rep 2017 Apr 6;7(1):681. doi: 10.1038/s41598-017-00766-9. PMID: 28386063Free PMC Article

Diagnosis

Mantere T, Tervasmäki A, Nurmi A, Rapakko K, Kauppila S, Tang J, Schleutker J, Kallioniemi A, Hartikainen JM, Mannermaa A, Nieminen P, Hanhisalo R, Lehto S, Suvanto M, Grip M, Jukkola-Vuorinen A, Tengström M, Auvinen P, Kvist A, Borg Å, Blomqvist C, Aittomäki K, Greenberg RA, Winqvist R, Nevanlinna H, Pylkäs K
Sci Rep 2017 Apr 6;7(1):681. doi: 10.1038/s41598-017-00766-9. PMID: 28386063Free PMC Article

Therapy

Guturi KKN, Bohgaki M, Bohgaki T, Srikumar T, Ng D, Kumareswaran R, El Ghamrasni S, Jeon J, Patel P, Eldin MS, Bristow R, Cheung P, Stewart GS, Raught B, Hakem A, Hakem R
Nat Commun 2016 Aug 25;7:12638. doi: 10.1038/ncomms12638. PMID: 27558965Free PMC Article

Prognosis

Dasouki MJ, Lushington GH, Hovanes K, Casey J, Gorre M
Am J Med Genet A 2011 Jul;155A(7):1654-60. Epub 2011 May 27 doi: 10.1002/ajmg.a.34080. PMID: 21626679Free PMC Article

Clinical prediction guides

Dasouki MJ, Lushington GH, Hovanes K, Casey J, Gorre M
Am J Med Genet A 2011 Jul;155A(7):1654-60. Epub 2011 May 27 doi: 10.1002/ajmg.a.34080. PMID: 21626679Free PMC Article

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