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Nestor-Guillermo progeria syndrome(NGPS)

MedGen UID:
462796
Concept ID:
C3151446
Disease or Syndrome
Synonyms: NGPS; PROGERIA SYNDROME, CHILDHOOD-ONSET, WITH OSTEOLYSIS
SNOMED CT: Nestor Guillermo progeria syndrome (773331001); NGPS - Nestor Guillermo progeria syndrome (773331001)
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).
 
Gene (location): BANF1 (11q13.1)
 
Monarch Initiative: MONDO:0013523
OMIM®: 614008
Orphanet: ORPHA280576

Definition

Nestor-Guillermo progeria syndrome (NGPS) is an autosomal recessive disorder characterized by lipoatrophy, osteoporosis, and very severe osteolysis. Patients have no cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia, but suffer profound skeletal abnormalities that affect their quality of life. Onset is after 2 years of age, and lifespan is relatively long (summary by Cabanillas et al., 2011). [from OMIM]

Clinical features

From HPO
Osteolytic defects of the distal phalanges of the hand
MedGen UID:
341480
Concept ID:
C1849547
Finding
Limited elbow movement
MedGen UID:
337930
Concept ID:
C1849955
Finding
Atherosclerosis
MedGen UID:
13948
Concept ID:
C0004153
Disease or Syndrome
A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Sinus tachycardia
MedGen UID:
11700
Concept ID:
C0039239
Disease or Syndrome
Heart rate of greater than 100 beats per minute.
Right bundle branch block
MedGen UID:
88445
Concept ID:
C0085615
Disease or Syndrome
A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.
Left atrial enlargement
MedGen UID:
536845
Concept ID:
C0238705
Finding
Increase in size of the left atrium.
Right atrial enlargement
MedGen UID:
677114
Concept ID:
C0748427
Disease or Syndrome
Increase in size of the right atrium.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
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).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Cavum septum pellucidum
MedGen UID:
327087
Concept ID:
C1840380
Finding
If the two laminae of the septum pellucidum are not fused then a fluid-filled space or cavum is present. The cavum septum pellucidum is present at birth but usually obliterates by the age of 3 to 6 months. It is up to 1cm in width and the walls are parallel. It is an enclosed space and is not part of the ventricular system or connected with the subarachnoid space.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Wide cranial sutures
MedGen UID:
140825
Concept ID:
C0410935
Finding
An abnormally increased width of the cranial sutures for age-related norms (generally resulting from delayed closure).
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Lipoatrophy
MedGen UID:
488959
Concept ID:
C1280433
Disease or Syndrome
Localized loss of fat tissue.
Progressive clavicular acroosteolysis
MedGen UID:
324869
Concept ID:
C1837757
Finding
Progressive bone resorption in the distal part of the clavicle.
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Enlarged cisterna magna
MedGen UID:
344031
Concept ID:
C1853377
Finding
Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.
Rib osteolysis
MedGen UID:
462799
Concept ID:
C3151449
Finding
Osteolysis (destruction of bone through bone resorption with removal or loss of calcium) localized to a rib.
Mandibular osteolysis
MedGen UID:
462800
Concept ID:
C3151450
Finding
Osteolysis (destruction of bone through bone resorption with removal or loss of calcium) localized to the mandible.
Delayed closure of the anterior fontanelle
MedGen UID:
825928
Concept ID:
C3840083
Finding
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
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.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
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.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Prominent superficial veins
MedGen UID:
324870
Concept ID:
C1837785
Finding
A condition in which superficial veins (i.e., veins just under the skin) are more conspicuous or noticeable than normal.
Sparse eyelashes
MedGen UID:
375151
Concept ID:
C1843300
Finding
Decreased density/number of eyelashes.
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Spotty hyperpigmentation
MedGen UID:
812509
Concept ID:
C3806179
Finding
Decreased serum leptin
MedGen UID:
373413
Concept ID:
C1837802
Finding
A decreased concentration of leptin in the blood.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNestor-Guillermo progeria syndrome
Follow this link to review classifications for Nestor-Guillermo progeria syndrome in Orphanet.

Recent clinical studies

Etiology

Díaz-López EJ, Sánchez-Iglesias S, Castro AI, Cobelo-Gómez S, Prado-Moraña T, Araújo-Vilar D, Fernandez-Pombo A
Int J Mol Sci 2024 Aug 28;25(17) doi: 10.3390/ijms25179324. PMID: 39273270Free PMC Article
Fisher HG, Patni N, Scheuerle AE
Am J Med Genet A 2020 Oct;182(10):2399-2402. Epub 2020 Aug 12 doi: 10.1002/ajmg.a.61777. PMID: 32783369

Diagnosis

Díaz-López EJ, Sánchez-Iglesias S, Castro AI, Cobelo-Gómez S, Prado-Moraña T, Araújo-Vilar D, Fernandez-Pombo A
Int J Mol Sci 2024 Aug 28;25(17) doi: 10.3390/ijms25179324. PMID: 39273270Free PMC Article
Fisher HG, Patni N, Scheuerle AE
Am J Med Genet A 2020 Oct;182(10):2399-2402. Epub 2020 Aug 12 doi: 10.1002/ajmg.a.61777. PMID: 32783369
Doubaj Y, De Sandre-Giovannoli A, Vera EV, Navarro CL, Elalaoui SC, Tajir M, Lévy N, Sefiani A
Am J Med Genet A 2012 Nov;158A(11):2881-7. Epub 2012 Sep 18 doi: 10.1002/ajmg.a.35557. PMID: 22991222
Cabanillas R, Cadiñanos J, Villameytide JA, Pérez M, Longo J, Richard JM, Alvarez R, Durán NS, Illán R, González DJ, López-Otín C
Am J Med Genet A 2011 Nov;155A(11):2617-25. Epub 2011 Sep 19 doi: 10.1002/ajmg.a.34249. PMID: 21932319

Prognosis

Doubaj Y, De Sandre-Giovannoli A, Vera EV, Navarro CL, Elalaoui SC, Tajir M, Lévy N, Sefiani A
Am J Med Genet A 2012 Nov;158A(11):2881-7. Epub 2012 Sep 18 doi: 10.1002/ajmg.a.35557. PMID: 22991222
Cabanillas R, Cadiñanos J, Villameytide JA, Pérez M, Longo J, Richard JM, Alvarez R, Durán NS, Illán R, González DJ, López-Otín C
Am J Med Genet A 2011 Nov;155A(11):2617-25. Epub 2011 Sep 19 doi: 10.1002/ajmg.a.34249. PMID: 21932319

Clinical prediction guides

Marcelot A, Rodriguez-Tirado F, Cuniasse P, Joiner ML, Miron S, Soshnev AA, Fang M, Pufall MA, Mathews KD, Moore SA, Zinn-Justin S, Geyer PK
Cells 2023 Mar 9;12(6) doi: 10.3390/cells12060847. PMID: 36980188Free PMC Article
Janssen A, Marcelot A, Breusegem S, Legrand P, Zinn-Justin S, Larrieu D
Nucleic Acids Res 2022 Sep 9;50(16):9260-9278. doi: 10.1093/nar/gkac726. PMID: 36039758Free PMC Article
Paquet N, Box JK, Ashton NW, Suraweera A, Croft LV, Urquhart AJ, Bolderson E, Zhang SD, O'Byrne KJ, Richard DJ
BMC Mol Biol 2014 Dec 12;15:27. doi: 10.1186/s12867-014-0027-z. PMID: 25495845Free PMC Article
Osorio FG, Ugalde AP, Mariño G, Puente XS, Freije JM, López-Otín C
Biochem Soc Trans 2011 Dec;39(6):1710-4. doi: 10.1042/BST20110677. PMID: 22103512
Cabanillas R, Cadiñanos J, Villameytide JA, Pérez M, Longo J, Richard JM, Alvarez R, Durán NS, Illán R, González DJ, López-Otín C
Am J Med Genet A 2011 Nov;155A(11):2617-25. Epub 2011 Sep 19 doi: 10.1002/ajmg.a.34249. PMID: 21932319

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