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Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome(HANAC)

MedGen UID:
382033
•Concept ID:
C2673195
•
Disease or Syndrome
Synonym: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps
SNOMED CT: Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome (702428000); Autosomal dominant familial hematuria, retinal arteriolar tortuosity, contractures (702428000); HANAC - hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (702428000); HANAC syndrome (702428000)
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.
Autosomal dominant inheritance (Orphanet)
 
Gene (location): COL4A1 (13q34)
 
Monarch Initiative: MONDO:0012726
OMIM®: 611773
Orphanet: ORPHA73229

Disease characteristics

Excerpted from the GeneReview: COL4A1-Related Disorders
The spectrum of COL4A1-related disorders includes: small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (retinal arterial tortuosity, Axenfeld-Rieger anomaly, cataract) and systemic findings (kidney involvement, muscle cramps, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia). On imaging studies, small-vessel brain disease is manifest as diffuse periventricular leukoencephalopathy, lacunar infarcts, microhemorrhage, dilated perivascular spaces, and deep intracerebral hemorrhages. Clinically, small-vessel brain disease manifests as infantile hemiparesis, seizures, single or recurrent hemorrhagic stroke, ischemic stroke, and isolated migraine with aura. Porencephaly (fluid-filled cavities in the brain detected by CT or MRI) is typically manifest as infantile hemiparesis, seizures, and intellectual disability; however, on occasion it can be an incidental finding. HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome usually associates asymptomatic small-vessel brain disease, cerebral large vessel involvement (i.e., aneurysms), and systemic findings involving the kidney, muscle, and small vessels of the eye. Two additional phenotypes include isolated retinal artery tortuosity and nonsyndromic autosomal dominant congenital cataract. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Emmanuelle Plaisier  |  Pierre Ronco   view full author information

Additional description

From MedlinePlus Genetics
Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. In people with HANAC syndrome, angiopathy affects several parts of the body. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage.

People with HANAC syndrome develop kidney disease (nephropathy). Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). Cysts can also form in one or both kidneys, and the cysts may grow larger over time.

Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). However, in people with HANAC syndrome, these aneurysms typically do not burst. About half of people with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).

Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. Muscle cramps can be spontaneous or triggered by exercise.

Individuals with HANAC syndrome also experience a variety of eye problems. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye.

Rarely, affected individuals will have a condition called Raynaud phenomenon in which the blood vessels in the fingers and toes temporarily narrow, restricting blood flow to the fingertips and the ends of the toes. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Raynaud phenomenon is typically triggered by changes in temperature and usually causes no long term damage.  https://medlineplus.gov/genetics/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome

Clinical features

From HPO
Hematuria
MedGen UID:
5488
•Concept ID:
C0018965
•
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
See: Feature record | Search on this feature
Renal insufficiency
MedGen UID:
332529
•Concept ID:
C1565489
•
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
See: Feature record | Search on this feature
Renal cyst
MedGen UID:
854361
•Concept ID:
C3887499
•
Disease or Syndrome
A fluid filled sac in the kidney.
See: Feature record | Search on this feature
Raynaud phenomenon
MedGen UID:
20474
•Concept ID:
C0034735
•
Disease or Syndrome
An episodic vasoconstriction resulting in discoloration of the skin and pain in the affected areas, often involving fingers or toes. Classically associated with triphasic color changes (white, blue, red) but may be biphasic. Often occurs in response to cold temperatures or emotional stress. May be primary or secondary to an underlying autoimmune disease.
See: Feature record | Search on this feature
Supraventricular arrhythmia
MedGen UID:
96544
•Concept ID:
C0428974
•
Disease or Syndrome
A type of arrhythmia that originates above the ventricles, whereby the electrical impulse propagates down the normal His Purkinje system similar to normal sinus rhythm.
See: Feature record | Search on this feature
Dilatation of the cerebral artery
MedGen UID:
1386760
•Concept ID:
C4476540
•
Anatomical Abnormality
The presence of a localized dilatation or ballooning of a cerebral artery.
See: Feature record | Search on this feature
Abnormal periventricular white matter morphology
MedGen UID:
435926
•Concept ID:
C2673431
•
Finding
A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.
See: Feature record | Search on this feature
Lacunar stroke
MedGen UID:
465269
•Concept ID:
C3178801
•
Disease or Syndrome
A stroke related to a small infarct (2-20 mm in diameter) in the deep cerebral white matter, basal ganglia, or pons, that is presumed to result from the occlusion of a single small perforating artery supplying the subcortical areas of the brain.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Muscle spasm
MedGen UID:
52431
•Concept ID:
C0037763
•
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
See: Feature record | Search on this feature
Elevated circulating creatine kinase concentration
MedGen UID:
69128
•Concept ID:
C0241005
•
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
See: Feature record | Search on this feature
Retinal hemorrhage
MedGen UID:
11210
•Concept ID:
C0035317
•
Pathologic Function
Hemorrhage occurring within the retina.
See: Feature record | Search on this feature
Retinal arteriolar tortuosity
MedGen UID:
1830276
•Concept ID:
C5779554
•
Finding
The presence of an increased number of twists and turns of the retinal arterioles.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
Follow this link to review classifications for Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome in Orphanet.

Recent clinical studies

Etiology

Clinical characteristics of muscle cramps in hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome associated with a novel COL4A1 pathogenic variant: A family case study.
Haga S, Takeguchi R, Tanaka R, Satake A, Makita Y, Yanagi K, Kaname T, Takahashi S
Brain Dev 2023 Aug;45(7):390-394. Epub 2023 Mar 14 doi: 10.1016/j.braindev.2023.02.008. PMID: 36922284

Diagnosis

Clinical characteristics of muscle cramps in hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome associated with a novel COL4A1 pathogenic variant: A family case study.
Haga S, Takeguchi R, Tanaka R, Satake A, Makita Y, Yanagi K, Kaname T, Takahashi S
Brain Dev 2023 Aug;45(7):390-394. Epub 2023 Mar 14 doi: 10.1016/j.braindev.2023.02.008. PMID: 36922284
Hereditary Angiopathy With Nephropathy, Aneurysm, and Muscle Cramps (HANAC) Syndrome Presenting to Neuro-Ophthalmology With Metamorphopsia.
Jordan MA, Pierpont ME, Johnston RH, Lee MS, McClelland CM
J Neuroophthalmol 2019 Dec;39(4):506-510. doi: 10.1097/WNO.0000000000000812. PMID: 31453918

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