Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

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). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	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).

See: Feature record | Search on this feature

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).

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Microcephaly

MedGen UID:: 1644158
•Concept ID:: C4551563
•: Finding

Head circumference below 2 standard deviations below the mean for age and gender.

See: Feature record | Search on this feature

Pulmonary fibrosis

MedGen UID:: 11028
•Concept ID:: C0034069
•: Disease or Syndrome

Replacement of normal lung tissues by fibroblasts and collagen.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Decreased circulating IgG level

MedGen UID:: 1720114
•Concept ID:: C5234937
•: Finding

An abnormally decreased level of immunoglobulin G (IgG) in blood.

See: Feature record | Search on this feature

Abnormal facial shape

MedGen UID:: 98409
•Concept ID:: C0424503
•: Finding

An abnormal morphology (form) of the face or its components.

See: Feature record | Search on this feature

Dry skin

MedGen UID:: 56250
•Concept ID:: C0151908
•: Sign or Symptom

Skin characterized by the lack of natural or normal moisture.

See: Feature record | Search on this feature

Increased sensitivity to ionizing radiation

MedGen UID:: 867472
•Concept ID:: C4021850
•: Finding

An abnormally increased sensitivity to the effects of ionizing radiation.

See: Feature record | Search on this feature

Show all Hide all

Abnormal cellular phenotype
- Increased sensitivity to ionizing radiation
Abnormality of head or neck
- Abnormal facial shape
Abnormality of the immune system
- Decreased circulating IgG level
- Immunodeficiency
Abnormality of the integument
- Dry skin
Abnormality of the musculoskeletal system
- Microcephaly
Abnormality of the nervous system
- Cerebellar ataxia
- Mild global developmental delay
Abnormality of the respiratory system
- Pulmonary fibrosis
Growth abnormality
- Short stature

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVRIDDLE syndrome

Autosomal recessive cerebellar ataxia due to a DNA repair defect
- RIDDLE syndrome

Recent clinical studies

Etiology

Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility.

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: 28386063 Free PMC Article

See all (1)

Diagnosis

Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility.

See all (1)

Therapy

RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation.

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: 27558965 Free PMC Article

See all (1)

Prognosis

The 3q29 microdeletion syndrome: report of three new unrelated patients and in silico "RNA binding" analysis of the 3q29 region.

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: 21626679 Free PMC Article

See all (1)

Clinical prediction guides

The 3q29 microdeletion syndrome: report of three new unrelated patients and in silico "RNA binding" analysis of the 3q29 region.

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: 21626679 Free PMC Article

See all (1)

MedGen

National Center for Biotechnology Information

Send to:

RIDDLE syndrome(RIDL)

Definition

Clinical features

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

Reviews

Related information

Recent activity