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Hutchinson-Gilford syndrome(HGPS)

MedGen UID:
46123
Concept ID:
C0033300
Disease or Syndrome
Synonyms: HGPS; Hutchinson-Gilford Progeria Syndrome; Progerin-producing progeroid laminopathy; Progeroid Laminopathies
SNOMED CT: Progeria (238870004); Hutchinson-Gilford syndrome (238870004); Progeria syndrome (238870004); Premature senility syndrome (238870004)
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): LMNA (1q22)
 
Monarch Initiative: MONDO:0008310
OMIM®: 176670
Orphanet: ORPHA740

Disease characteristics

Excerpted from the GeneReview: Hutchinson-Gilford Progeria Syndrome
Hutchinson-Gilford progeria syndrome (HGPS) is characterized by clinical features that typically develop in childhood and resemble some features of accelerated aging. Children with HGPS usually appear normal at birth. Profound failure to thrive occurs during the first year. Characteristic facial features include head that is disproportionately large for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the upper and lower lips, small mouth, and retro- and micrognathia. Common features include loss of subcutaneous fat, delayed eruption and loss of primary teeth, abnormal skin with small outpouchings over the abdomen and upper thighs, alopecia, nail dystrophy, coxa valga, and progressive joint contractures. Later findings include low-frequency conductive hearing loss, dental crowding, and partial lack of secondary tooth eruption. Motor and mental development is normal. Death occurs as a result of complications of severe atherosclerosis, either cardiac disease (myocardial infarction or heart failure) or cerebrovascular disease (stroke), generally between ages six and 20 years (average 14.5 years) without lonafarnib treatment or cardiac surgery intervention. Average life span is extended to approximately 17-19.5 years with lonafarnib therapy. [from GeneReviews]
Authors:
Leslie B Gordon  |  W Ted Brown  |  Francis S Collins   view full author information

Additional descriptions

From OMIM
Hutchinson-Gilford progeria syndrome is a rare disorder characterized by short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early death. Cognitive development is normal. Onset is usually within the first year of life (review by Hennekam, 2006). The designation Hutchinson-Gilford progeria syndrome appears to have been first used by DeBusk (1972). A subset of patients with heterozygous mutations in the LMNA gene and a phenotype similar to HGPS have shown onset of the disorder in late childhood or in the early teenage years, and have longer survival than observed in classic HGPS (Chen et al., 2003; Hegele, 2003). Other disorders with a less severe, but overlapping phenotype include mandibuloacral dysplasia (MADA; 248370), an autosomal disorder caused by homozygous or compound heterozygous mutations in the LMNA gene, dilated cardiomyopathy with hypergonadotropic hypogonadism (212112), caused by heterozygous mutation in the LMNA gene, and Werner syndrome (277700), an autosomal recessive progeroid syndrome caused by homozygous or compound heterozygous mutations in the RECQL2 gene (604611).  http://www.omim.org/entry/176670
From MedlinePlus Genetics
Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not affect intellectual development or the development of motor skills such as sitting, standing, and walking.

People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals.  https://medlineplus.gov/genetics/condition/hutchinson-gilford-progeria-syndrome

Clinical features

From HPO
Angina pectoris
MedGen UID:
1929
Concept ID:
C0002962
Sign or Symptom
Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Myocardial infarction
MedGen UID:
10150
Concept ID:
C0027051
Disease or Syndrome
Necrosis of the myocardium caused by an obstruction of the blood supply to the heart and often associated with chest pain, shortness of breath, palpitations, and anxiety as well as characteristic EKG findings and elevation of serum markers including creatine kinase-MB fraction and troponin.
Premature coronary artery atherosclerosis
MedGen UID:
356830
Concept ID:
C1867743
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries before age of 45.
Precocious atherosclerosis
MedGen UID:
867292
Concept ID:
C4021654
Pathologic Function
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Absence of subcutaneous fat
MedGen UID:
69138
Concept ID:
C0241267
Finding
Lack of subcutaneous adipose tissue.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Generalized osteoporosis
MedGen UID:
1639139
Concept ID:
C4551680
Disease or Syndrome
Osteolysis
MedGen UID:
1648424
Concept ID:
C4721411
Pathologic Function
Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHutchinson-Gilford syndrome
Follow this link to review classifications for Hutchinson-Gilford syndrome in Orphanet.

Professional guidelines

PubMed

Piekarowicz K, Machowska M, Dzianisava V, Rzepecki R
Cells 2019 Jan 25;8(2) doi: 10.3390/cells8020088. PMID: 30691039Free PMC Article
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Recent clinical studies

Etiology

Messner M, Ghadge SK, Schuetz T, Seiringer H, Pölzl G, Zaruba MM
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Diagnosis

Mirg S, Pednekar S
J Assoc Physicians India 2024 Oct;72(10):91-92. doi: 10.59556/japi.72.0702. PMID: 39390869
de Paula Rodrigues GH, das Eiras Tâmega I, Duque G, Spinola Dias Neto V
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Badame AJ
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Therapy

Motegi S, Uchiyama A, Yamada K, Ogino S, Yokoyama Y, Perera B, Takeuchi Y, Ishikawa O
Exp Dermatol 2016 Aug;25 Suppl 3:20-7. doi: 10.1111/exd.13086. PMID: 27539898
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Kamenisch Y, Berneburg M
J Investig Dermatol Symp Proc 2009 Aug;14(1):8-14. doi: 10.1038/jidsymp.2009.6. PMID: 19675546

Prognosis

Mirg S, Pednekar S
J Assoc Physicians India 2024 Oct;72(10):91-92. doi: 10.59556/japi.72.0702. PMID: 39390869
Badame AJ
Arch Dermatol 1989 Apr;125(4):540-4. PMID: 2649013

Clinical prediction guides

Motegi S, Yokoyama Y, Uchiyama A, Ogino S, Takeuchi Y, Yamada K, Hattori T, Hashizume H, Ishikawa Y, Goto M, Ishikawa O
J Dermatol 2014 Dec;41(12):1047-52. Epub 2014 Oct 20 doi: 10.1111/1346-8138.12657. PMID: 25327215
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