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Sneddon syndrome(SNDNS)

MedGen UID:
76449
Concept ID:
C0282492
Disease or Syndrome
Synonyms: Cerebro-vascular lesions and livedo reticularis; Idiopathic livedo reticularis with systemic involvement; Livedo reticularis and cerebrovascular accidents; SNDNS; Sneddon's syndrome
SNOMED CT: Livedo reticularis and cerebrovascular accident syndrome (716745004); Sneddon syndrome (716745004); Ehrmann Sneddon syndrome (716745004); Livedo racemosa and cerebrovascular accident (716745004); Idiopathic livedo reticularis with systemic involvement (238776001)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): ADA2 (22q11.1)
 
Monarch Initiative: MONDO:0008436
OMIM®: 182410
Orphanet: ORPHA820

Definition

Sneddon syndrome is a noninflammatory arteriopathy characterized by onset of livedo reticularis in the second decade and onset of cerebrovascular disease in early adulthood (summary by Bras et al., 2014). Livedo reticularis occurs also with polyarteritis nodosa, systemic lupus erythematosus, and central thrombocythemia, any one of which may be accompanied by cerebrovascular accidents (Bruyn et al., 1987). [from OMIM]

Additional description

From MedlinePlus Genetics
Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues. Signs and symptoms can begin anytime from early childhood to adulthood. The severity of the disorder also varies, even among affected individuals in the same family.

ADA2 deficiency is sometimes described as a form of polyarteritis nodosa (PAN), a disorder that causes inflammation of blood vessels throughout the body (systemic vasculitis). However, not all researchers classify ADA2 deficiency as a type of PAN.

Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, ADA2 deficiency causes abnormal, unprovoked inflammation that can damage the body's tissues and organs, particularly blood vessels. (Inflammation of blood vessels is known as vasculitis.) Other tissues affected by abnormal inflammation can include the skin, gastrointestinal system, liver, kidneys, and nervous system. Depending on the severity and location of the inflammation, the disorder can cause disability or be life-threatening.

Signs and symptoms that can occur with ADA2 deficiency include fevers that are intermittent, meaning they come and go; areas of net-like, mottled skin discoloration called livedo racemosa; an enlarged liver and spleen (hepatosplenomegaly); and recurrent strokes affecting structures deep in the brain that can start in the first few years of life. In some people, ADA2 deficiency causes additional immune system abnormalities that increase the risk of bacterial and viral infections.  https://medlineplus.gov/genetics/condition/adenosine-deaminase-2-deficiency

Clinical features

From HPO
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Cerebral hemorrhage
MedGen UID:
423648
Concept ID:
C2937358
Pathologic Function
Hemorrhage into the parenchyma of the brain.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Hemiplegia
MedGen UID:
9196
Concept ID:
C0018991
Sign or Symptom
Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body.
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Ischemic stroke
MedGen UID:
215292
Concept ID:
C0948008
Disease or Syndrome
A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. It is said to be the third leading cause of death in the United States. Gunel and Lifton (1996) noted that about 20% of strokes are hemorrhagic, resulting in bleeding into the brain. Ischemic strokes, resulting from vascular occlusion, account for the majority of strokes. Bersano et al. (2008) reviewed genetic polymorphisms that have been implicated in the development of stroke. Candidate genes include those involved in hemostasis (see, e.g., F5; 612309), the renin-angiotensin-aldosterone system (see, e.g., ACE; 106180), homocysteine (see, e.g., MTHFR; 607093), and lipoprotein metabolism (see, e.g., APOE; 107741). See also hemorrhagic stroke, or intracerebral hemorrhage (ICH; 614519).
Impaired distal tactile sensation
MedGen UID:
867225
Concept ID:
C4021583
Finding
A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Antiphospholipid antibody positivity
MedGen UID:
866404
Concept ID:
C4019436
Finding
The presence of circulating autoantibodies to phospholipids.
Livedo reticularis
MedGen UID:
43223
Concept ID:
C0085642
Disease or Syndrome
Livedo reticularis is characterized by the presence of a bluish purple, mottled or netlike pattern in unbroken circles on the skin. Exposure to cold environments usually intensifies the vascular pattern. Presumably, the condition results from slow or stagnant blood flow, vessel-wall pathology, and decreased oxygen tension.
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin.
Cutis marmorata
MedGen UID:
78093
Concept ID:
C0263401
Disease or Syndrome
A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather.
Livedo
MedGen UID:
568434
Concept ID:
C0332579
Finding
A reddish-blue mottled condition of skin caused by inflammation of the cutaneous blood vessels.
Livedo racemosa
MedGen UID:
1778101
Concept ID:
C5441660
Sign or Symptom
Livedo racemosa describes a reddish-blue mottling of the skin in an irregular, reticular pattern. It differs from the more common livedo reticularis by its shape. Livedo racemosa consists of broken circular segments resulting in a seemingly larger pattern, as opposed to the fine, regular, complete network of livedo reticularis. Livedo racemosa results from permanent impairment of peripheral blood flow and, unlike livedo reticularis, it persists on warming.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSneddon syndrome
Follow this link to review classifications for Sneddon syndrome in Orphanet.

Professional guidelines

PubMed

Mitri F, Enk A, Bersano A, Kraemer M
Eur J Neurol 2020 Oct;27(10):1832-1843. Epub 2020 Jul 2 doi: 10.1111/ene.14390. PMID: 32526049
Collantes-Rodríguez C, Jiménez-Gallo D, Arjona-Aguilera C, Ossorio-García L, Linares-Barrios M
JAMA Dermatol 2016 Jun 1;152(6):726-7. doi: 10.1001/jamadermatol.2016.0162. PMID: 26982963

Recent clinical studies

Etiology

Bersano A, Kraemer M, Burlina A, Mancuso M, Finsterer J, Sacco S, Salvarani C, Caputi L, Chabriat H, Oberstein SL, Federico A, Lasserve ET, Hunt D, Dichgans M, Arnold M, Debette S, Markus HS
J Neurol 2021 Aug;268(8):2780-2807. Epub 2020 Apr 21 doi: 10.1007/s00415-020-09836-x. PMID: 32318851
Samanta D, Cobb S, Arya K
J Stroke Cerebrovasc Dis 2019 Aug;28(8):2098-2108. Epub 2019 May 31 doi: 10.1016/j.jstrokecerebrovasdis.2019.05.013. PMID: 31160219
Martinez-Mera C, Fraga J, Capusan TM, Herrero-Moyano M, Godoy-Trapero A, Gonzales Perez Y, Llamas-Velasco M
G Ital Dermatol Venereol 2017 Dec;152(6):615-637. Epub 2017 Jul 28 doi: 10.23736/S0392-0488.17.05727-3. PMID: 28845953
Al Aboud D, Broshtilova V, Al Aboud K, Al Hawsawi K
Acta Dermatovenerol Alp Pannonica Adriat 2005 Mar;14(1):9-14. PMID: 15818440
Green D
Top Stroke Rehabil 2003 Fall;10(3):21-33. doi: 10.1310/L9KD-N5N8-69X0-08QK. PMID: 14681817

Diagnosis

Demartini ZJ, de Araujo WJB, Lange MC
Neurol India 2023 Jul-Aug;71(4):864-865. doi: 10.4103/0028-3886.383840. PMID: 37635563
Bersano A, Kraemer M, Burlina A, Mancuso M, Finsterer J, Sacco S, Salvarani C, Caputi L, Chabriat H, Oberstein SL, Federico A, Lasserve ET, Hunt D, Dichgans M, Arnold M, Debette S, Markus HS
J Neurol 2021 Aug;268(8):2780-2807. Epub 2020 Apr 21 doi: 10.1007/s00415-020-09836-x. PMID: 32318851
Silawy A, Odeh M, Borissovsky N, Slobodin G
Isr Med Assoc J 2020 Oct;22(10):657. PMID: 33070495
Samanta D, Cobb S, Arya K
J Stroke Cerebrovasc Dis 2019 Aug;28(8):2098-2108. Epub 2019 May 31 doi: 10.1016/j.jstrokecerebrovasdis.2019.05.013. PMID: 31160219
Llamas-Velasco M, Alegría V, Santos-Briz Á, Cerroni L, Kutzner H, Requena L
Am J Dermatopathol 2017 Sep;39(9):637-662. doi: 10.1097/DAD.0000000000000766. PMID: 27759698

Therapy

Kong SS, Azarfar A, Bhanusali N
Rheumatol Int 2021 May;41(5):987-991. Epub 2020 Jun 12 doi: 10.1007/s00296-020-04625-1. PMID: 32533291
Fiore A, Ternacle J, Piscitelli M, Fardet L, Mongardon N
Perfusion 2020 Oct;35(7):710-711. Epub 2020 Jan 20 doi: 10.1177/0267659119899333. PMID: 31957552
Almutlaq A, Alshurem M, Levesque-Roy M, Massie R
Neurology 2019 Sep 17;93(12):e1227-e1228. doi: 10.1212/WNL.0000000000008137. PMID: 31527109
Samanta D, Cobb S, Arya K
J Stroke Cerebrovasc Dis 2019 Aug;28(8):2098-2108. Epub 2019 May 31 doi: 10.1016/j.jstrokecerebrovasdis.2019.05.013. PMID: 31160219
Green D
Top Stroke Rehabil 2003 Fall;10(3):21-33. doi: 10.1310/L9KD-N5N8-69X0-08QK. PMID: 14681817

Prognosis

Laurent C, Ricard L, Nguyen Y, Boffa JJ, Rondeau E, Gerotziafas G, Elalamy I, Deriaz S, De Moreuil C, Planche V, Johanet C, Millot F, Fain O, Mekinian A
RMD Open 2023 Mar;9(1) doi: 10.1136/rmdopen-2022-002534. PMID: 37001919Free PMC Article
Samanta D, Cobb S, Arya K
J Stroke Cerebrovasc Dis 2019 Aug;28(8):2098-2108. Epub 2019 May 31 doi: 10.1016/j.jstrokecerebrovasdis.2019.05.013. PMID: 31160219
Martinez-Mera C, Fraga J, Capusan TM, Herrero-Moyano M, Godoy-Trapero A, Gonzales Perez Y, Llamas-Velasco M
G Ital Dermatol Venereol 2017 Dec;152(6):615-637. Epub 2017 Jul 28 doi: 10.23736/S0392-0488.17.05727-3. PMID: 28845953
Wu S, Xu Z, Liang H
Orphanet J Rare Dis 2014 Dec 31;9:215. doi: 10.1186/s13023-014-0215-4. PMID: 25551694Free PMC Article
Dutra LA, Braga-Neto P, Pedroso JL, Barsottini OG
Einstein (Sao Paulo) 2012 Apr-Jun;10(2):230-2. doi: 10.1590/s1679-45082012000200018. PMID: 23052460

Clinical prediction guides

Yilmaz E, Arsava EM, Gocmen R, Oguz KK, Arat A, Topcuoglu MA
Neurol Sci 2021 Jun;42(6):2363-2369. Epub 2020 Oct 13 doi: 10.1007/s10072-020-04621-0. PMID: 33047201
Ghislain L, Aydin S, Marot L, Demoulin N, Morelle J
Clin Nephrol 2020 Apr;93(4):209-214. doi: 10.5414/CN109748. PMID: 31661059
Santo GC, Baldeiras I, Guerreiro R, Ribeiro JA, Cunha R, Youngstein T, Nanthapisal S, Leitão J, Fernandes C, Caramelo F, Almeida MDR, Brás J, Santana I; Centro Hospitalar e Universitário de Coimbra
Cerebrovasc Dis 2018;46(5-6):257-264. Epub 2019 Jan 15 doi: 10.1159/000495794. PMID: 30645994
Bottin L, Francès C, de Zuttere D, Boëlle PY, Muresan IP, Alamowitch S
Ann Neurol 2015 May;77(5):817-29. Epub 2015 Mar 13 doi: 10.1002/ana.24382. PMID: 25628239
Francès C, Piette JC
J Autoimmun 2000 Sep;15(2):139-43. doi: 10.1006/jaut.2000.0418. PMID: 10968900

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