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Grange syndrome(GRNG)

MedGen UID:
355427
Concept ID:
C1865267
Disease or Syndrome
Synonyms: GRANGE OCCLUSIVE ARTERIAL SYNDROME; GRNG
SNOMED CT: Progressive arterial occlusive disease, hypertension, heart defect, bone fragility, brachysyndactyly syndrome (717824007); Grange syndrome (717824007); Grange occlusive arterial syndrome (717824007)
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 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.
 
Gene (location): YY1AP1 (1q22)
 
Monarch Initiative: MONDO:0011243
OMIM®: 602531
Orphanet: ORPHA79094

Definition

Grange syndrome (GRNG) is a rare early-onset disease characterized by hypertension and multifocal stenoocclusive lesions of renal, cerebral, and abdominal arteries. Bone fragility, syndactyly, brachydactyly, congenital heart defects, and learning disabilities have been reported with variable expressivity and incomplete penetrance (summary by Rath et al., 2019). [from OMIM]

Additional description

From MedlinePlus Genetics
Grange syndrome is a rare condition that primarily affects the blood vessels. It is characterized by narrowing (stenosis) or blockage (occlusion) of arteries that supply blood to various organs and tissues, including the kidneys, brain, and heart. Stenosis or occlusion of the arteries that supply blood to the kidneys (renal arteries) can result in chronic high blood pressure (hypertension). Blockage of the arteries that carry blood to the brain (cerebral arteries) can cause a stroke.

Additional features of Grange syndrome can include short fingers and toes (brachydactyly), fusion of some of the fingers or toes (syndactyly), fragile bones that are prone to breakage, and learning disabilities. Most people with this disorder also have heart defects that are present from birth.  https://medlineplus.gov/genetics/condition/grange-syndrome

Clinical features

From HPO
Renovascular hypertension
MedGen UID:
43786
Concept ID:
C0020545
Disease or Syndrome
The presence of hypertension related to stenosis of the renal artery.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Finger clinodactyly
MedGen UID:
120550
Concept ID:
C0265610
Congenital Abnormality
Familial isolated clinodactyly of fingers is a rare, genetic, non-syndromic, congenital limb malformation disorder characterized by angulation of a digit in the radio-ulnar (coronal) plane, away from the axis of joint flexion-extension, in several members of a single family with no other associated manifestations. Deviation is usually bilateral and commonly involves the fifth finger. Affected digits present trapezoidal or delta-shaped phalanges on imaging.
Carotid artery stenosis
MedGen UID:
785
Concept ID:
C0007282
Disease or Syndrome
Narrowing of the carotid arteries.
Renal artery stenosis
MedGen UID:
19727
Concept ID:
C0035067
Disease or Syndrome
The presence of stenosis of the renal artery.
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).
Coronary artery stenosis
MedGen UID:
66859
Concept ID:
C0242231
Disease or Syndrome
Abnormal narrowing of the coronary artery.
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
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.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Increased susceptibility to fractures
MedGen UID:
234655
Concept ID:
C1390474
Finding
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.

Term Hierarchy

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

Professional guidelines

PubMed

Burton BK, Shively V, Quadri A, Warn L, Burton J, Grange DK, Christensen K, Groepper D, Ashbaugh L, Ehrhardt J, Basheeruddin K
Mol Genet Metab 2023 Sep-Oct;140(1-2):107557. Epub 2023 Mar 6 doi: 10.1016/j.ymgme.2023.107557. PMID: 36907694
Kirk EP, Scurr I, van Haaften G, van Haelst MM, Nichols CG, Williams M, Smithson SF, Grange DK
Eur J Hum Genet 2017 Apr;25(4) Epub 2017 Jan 4 doi: 10.1038/ejhg.2016.185. PMID: 28051078Free PMC Article
Le Grange D, Loeb KL
Early Interv Psychiatry 2007 Feb;1(1):27-39. doi: 10.1111/j.1751-7893.2007.00007.x. PMID: 21352106

Recent clinical studies

Etiology

Raggio V, Dell'Oca N, Simoes C, Tapié A, Medici C, Costa G, Rodriguez S, Greif G, Garrone E, Rovella ML, Gonzalez V, Halty M, González G, Shin JY, Shin SY, Kim C, Seo JS, Graña M, Naya H, Spangenberg L
Hum Genomics 2021 May 10;15(1):28. doi: 10.1186/s40246-021-00328-1. PMID: 33971976Free PMC Article
Guo DC, Duan XY, Regalado ES, Mellor-Crummey L, Kwartler CS, Kim D, Lieberman K, de Vries BBA, Pfundt R, Schinzel A, Kotzot D, Shen X, Yang ML; University of Washington Center for Mendelian Genomics, Bamshad MJ, Nickerson DA, Gornik HL, Ganesh SK, Braverman AC, Grange DK, Milewicz DM
Am J Hum Genet 2017 Jan 5;100(1):21-30. Epub 2016 Dec 8 doi: 10.1016/j.ajhg.2016.11.008. PMID: 27939641Free PMC Article

Diagnosis

Raggio V, Dell'Oca N, Simoes C, Tapié A, Medici C, Costa G, Rodriguez S, Greif G, Garrone E, Rovella ML, Gonzalez V, Halty M, González G, Shin JY, Shin SY, Kim C, Seo JS, Graña M, Naya H, Spangenberg L
Hum Genomics 2021 May 10;15(1):28. doi: 10.1186/s40246-021-00328-1. PMID: 33971976Free PMC Article
Ciuffetelli Alamo IV, Kwartler CS, Regalado ER, Afifi RO, Parkash S, Rideout A, Guo DC, Milewicz DM
Am J Med Genet A 2019 Dec;179(12):2500-2505. Epub 2019 Oct 21 doi: 10.1002/ajmg.a.61379. PMID: 31633303
Volonghi I, Frigerio M, Mardighian D, Gasparotti R, Del Zotto E, Giossi A, Costa P, Poli L, Jeannin G, Gregorini GA, Padovani A, Pezzini A
Am J Med Genet A 2012 Nov;158A(11):2894-8. Epub 2012 Sep 17 doi: 10.1002/ajmg.a.35593. PMID: 22987684
Molloy ES, Langford CA
Curr Opin Rheumatol 2008 Jan;20(1):29-34. doi: 10.1097/BOR.0b013e3282f1dcf2. PMID: 18281854

Prognosis

Raggio V, Dell'Oca N, Simoes C, Tapié A, Medici C, Costa G, Rodriguez S, Greif G, Garrone E, Rovella ML, Gonzalez V, Halty M, González G, Shin JY, Shin SY, Kim C, Seo JS, Graña M, Naya H, Spangenberg L
Hum Genomics 2021 May 10;15(1):28. doi: 10.1186/s40246-021-00328-1. PMID: 33971976Free PMC Article
Rath M, Spiegler S, Strom TM, Trenkler J, Kroisel PM, Felbor U
Am J Med Genet A 2019 Feb;179(2):295-299. Epub 2018 Dec 17 doi: 10.1002/ajmg.a.60700. PMID: 30556293Free PMC Article
Weymann S, Yonekawa Y, Khan N, Martin E, Heppner FL, Schinzel A, Kotzot D
Am J Med Genet 2001 Mar 15;99(3):190-5. doi: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1138>3.0.co;2-r. PMID: 11241488

Clinical prediction guides

Raggio V, Dell'Oca N, Simoes C, Tapié A, Medici C, Costa G, Rodriguez S, Greif G, Garrone E, Rovella ML, Gonzalez V, Halty M, González G, Shin JY, Shin SY, Kim C, Seo JS, Graña M, Naya H, Spangenberg L
Hum Genomics 2021 May 10;15(1):28. doi: 10.1186/s40246-021-00328-1. PMID: 33971976Free PMC Article
Saida K, Kim CA, Ceroni JRM, Bertola DR, Honjo RS, Mitsuhashi S, Takata A, Mizuguchi T, Miyatake S, Miyake N, Matsumoto N
J Hum Genet 2019 Sep;64(9):885-890. Epub 2019 Jul 4 doi: 10.1038/s10038-019-0626-0. PMID: 31270375
Rath M, Spiegler S, Strom TM, Trenkler J, Kroisel PM, Felbor U
Am J Med Genet A 2019 Feb;179(2):295-299. Epub 2018 Dec 17 doi: 10.1002/ajmg.a.60700. PMID: 30556293Free PMC Article

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