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Metatropic dysplasia(MTD)

MedGen UID:
82699
Concept ID:
C0265281
Congenital Abnormality
Synonyms: Metatropic dwarfism; Metatropic dysplasia, nonlethal dominant; MTD
SNOMED CT: Metatropic dwarfism syndrome (22764001); Metatropic dwarf (22764001); Metatropic dysplasia group (22764001); Metatropic dwarfism (22764001); Metatropic dysplasia (22764001)
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): TRPV4 (12q24.11)
 
Monarch Initiative: MONDO:0007986
OMIM®: 156530
Orphanet: ORPHA2635

Disease characteristics

Excerpted from the GeneReview: Autosomal Dominant TRPV4 Disorders
The autosomal dominant TRPV4 disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within each group is considerable. Affected individuals typically have either neuromuscular or skeletal manifestations alone, and in only rare instances an overlap syndrome has been reported. The three autosomal dominant neuromuscular disorders (mildest to most severe) are: Charcot-Marie-Tooth disease type 2C. Scapuloperoneal spinal muscular atrophy. Congenital distal spinal muscular atrophy. The autosomal dominant neuromuscular disorders are characterized by a congenital-onset, static, or later-onset progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six autosomal dominant skeletal dysplasias (mildest to most severe) are: Familial digital arthropathy-brachydactyly. Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the autosomal dominant TRPV4 disorders life span is normal; in the most severe it is shortened. Bilateral progressive sensorineural hearing loss (SNHL) can occur with both autosomal dominant neuromuscular disorders and skeletal dysplasias. [from GeneReviews]
Authors:
Brett A McCray  |  Alice Schindler  |  Julie E Hoover-Fong, et. al.   view full author information

Additional descriptions

From OMIM
Metatropic dysplasia (MTD) is characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis. Radiologic features include severe platyspondyly, severe metaphyseal enlargement, and shortening of long bones (Genevieve et al., 2008).  http://www.omim.org/entry/156530
From MedlinePlus Genetics
Metatropic dysplasia is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term "metatropic" is derived from the Greek word "metatropos," which means "changing patterns." This name reflects the fact that the skeletal abnormalities associated with the condition change over time.

Affected infants are born with a narrow chest and unusually short arms and legs with dumbbell-shaped long bones. Beginning in early childhood, people with this condition develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). The curvature worsens with time and tends to be resistant to treatment. Because of the severe kyphoscoliosis, affected individuals may ultimately have a very short torso in relation to the length of their arms and legs.

Some people with metatropic dysplasia are born with an elongated tailbone known as a coccygeal tail; it is made of a tough but flexible tissue called cartilage. The coccygeal tail usually shrinks over time. Other skeletal problems associated with metatropic dysplasia include flattened bones of the spine (platyspondyly); excessive movement of spinal bones in the neck that can damage the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint deformities called contractures that restrict the movement of joints in the shoulders, elbows, hips, and knees. Beginning early in life, affected individuals can also develop a degenerative form of arthritis that causes joint pain and further restricts movement.

The signs and symptoms of metatropic dysplasia can vary from relatively mild to life-threatening. In the most severe cases, the narrow chest and spinal abnormalities prevent the lungs from expanding fully, which restricts breathing. Researchers formerly recognized several distinct forms of metatropic dysplasia based on the severity of the condition's features. The forms included a mild type, a classic type, and a lethal type. However, all of these forms are now considered to be part of a single condition with a spectrum of overlapping signs and symptoms.  https://medlineplus.gov/genetics/condition/metatropic-dysplasia

Clinical features

From HPO
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.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Flat acetabular roof
MedGen UID:
373340
Concept ID:
C1837485
Finding
Flattening of the superior part of the acetabulum, which is a cup-shaped cavity at the base of the hipbone into which the ball-shaped head of the femur fits. The acetabular roof thereby appears horizontal rather than arched, as it normally does.
Short finger
MedGen UID:
334977
Concept ID:
C1844548
Anatomical Abnormality
Abnormally short finger associated with developmental hypoplasia.
Hyperplasia of the femoral trochanters
MedGen UID:
478750
Concept ID:
C3277120
Finding
Flared humeral metaphysis
MedGen UID:
892657
Concept ID:
C4020912
Anatomical Abnormality
Flaring (increase of width with a splayed appearance) of the humeral metaphysis.
Dumbbell-shaped femur
MedGen UID:
870603
Concept ID:
C4025052
Anatomical Abnormality
The femur is shortened and displays flaring (widening) of the metaphyses.
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Disproportionate short-limb short stature
MedGen UID:
342370
Concept ID:
C1849937
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Narrow greater sciatic notch
MedGen UID:
154353
Concept ID:
C0566888
Finding
A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Disproportionate short-trunk short stature
MedGen UID:
337580
Concept ID:
C1846435
Finding
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.
Odontoid hypoplasia
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Flaring of rib cage
MedGen UID:
381496
Concept ID:
C1854780
Finding
The presence of wide, concave anterior rib ends.
Anisospondyly
MedGen UID:
387741
Concept ID:
C1857101
Finding
Abnormally increased variability of the size of the vertebral bodies.
Enlarged joints
MedGen UID:
347068
Concept ID:
C1859111
Finding
Increase in size of one or more joints.
Cone-shaped epiphysis
MedGen UID:
351282
Concept ID:
C1865037
Finding
Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.
Cupped ribs
MedGen UID:
351284
Concept ID:
C1865039
Finding
Wide, concave rib end.
Flared iliac wing
MedGen UID:
356097
Concept ID:
C1865841
Finding
Widening of the ilium ala, that is of the wing of the ilium, combined with external rotation, leading to a flared appearance of the iliac wing.
Relatively short spine
MedGen UID:
478744
Concept ID:
C3277114
Finding
Long coccyx
MedGen UID:
478746
Concept ID:
C3277116
Finding
Caudal appendage
MedGen UID:
478747
Concept ID:
C3277117
Finding
The presence of a tail-like skin appendage located adjacent to the sacrum.
Halberd-shaped pelvis
MedGen UID:
478749
Concept ID:
C3277119
Finding
An anomalous radiographic appearance of the developing pelvis, in which the greater ischiadic noth (incisura ischiadica major) is shallow and the pelvis takes on the appearance said to resemble a halberd (a weapon especially of the 15th and 16th centuries consisting typically of a battle-ax and pike mounted on a handle).
Dumbbell-shaped metaphyses
MedGen UID:
478753
Concept ID:
C3277123
Finding
Absent primary metaphyseal spongiosa
MedGen UID:
478756
Concept ID:
C3277126
Finding
Abnormal metaphyseal vascular invasion
MedGen UID:
478757
Concept ID:
C3277127
Finding
Abnormal enchondral ossification
MedGen UID:
871155
Concept ID:
C4025628
Anatomical Abnormality
An abnormality of the process of endochondral ossification, which is a type of replacement ossification in which bone tissue replaces cartilage.
Flared femoral metaphysis
MedGen UID:
871197
Concept ID:
C4025674
Anatomical Abnormality
Clavicular pseudarthrosis
MedGen UID:
1814348
Concept ID:
C5676779
Pathologic Function
A developmental defect in a the clavicule leading to bending and pathologic fracture, with inability to form a normal bony callus with subsequent fibrous nonunion, leading to the pseudarthrosis (or false joint).
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Fetal akinesia deformation sequence 1
MedGen UID:
220903
Concept ID:
C1276035
Disease or Syndrome
Decreased fetal activity associated with multiple joint contractures, facial anomalies and pulmonary hypoplasia. Ultrasound examination may reveal polyhydramnios, ankylosis, scalp edema, and decreased chest movements (reflecting pulmonary hypoplasia).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMetatropic dysplasia
Follow this link to review classifications for Metatropic dysplasia in Orphanet.

Professional guidelines

PubMed

Nguyen DB, Khirani S, Griffon L, Baujat G, Michot C, Marzin P, Rondeau S, Luscan R, Couloigner V, Pejin Z, Zerah M, Cormier-Daire V, Fauroux B
Am J Med Genet A 2021 Jul;185(7):2108-2118. Epub 2021 Apr 28 doi: 10.1002/ajmg.a.62236. PMID: 33908178

Recent clinical studies

Etiology

Bauer JM, Ditro CP, Mackenzie WG
Spine Deform 2019 May;7(3):494-500. doi: 10.1016/j.jspd.2018.09.007. PMID: 31053321
Theroux MC, Lopez M, Olszewsky PJ, DiCindio S, Arai L, Ditro C, Bober MB, Olla OO, Uejima T, West DW, Mackenzie WG
Paediatr Anaesth 2017 Jun;27(6):596-603. Epub 2017 Mar 21 doi: 10.1111/pan.13101. PMID: 28321993
Nishimura G, Lausch E, Savarirayan R, Shiba M, Spranger J, Zabel B, Ikegawa S, Superti-Furga A, Unger S
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):190-204. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31335. PMID: 22791502
Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH
Am J Hum Genet 2009 Mar;84(3):307-15. Epub 2009 Feb 19 doi: 10.1016/j.ajhg.2009.01.021. PMID: 19232556Free PMC Article
Hall CM, Elçioglu NH
Pediatr Radiol 2004 Jan;34(1):66-74. Epub 2003 Oct 18 doi: 10.1007/s00247-003-1063-x. PMID: 14566438

Diagnosis

Tchio Tchoumba MA, Bai Y, Jin R, Yu X, Male M
Orthop Surg 2020 Feb;12(1):333-336. Epub 2019 Dec 6 doi: 10.1111/os.12546. PMID: 31808622Free PMC Article
Bargiacchi S, Della Monica M, Biagiotti R, Andreucci E, Ciabattoni S, Poggi P, Di Maurizio M, Defilippi C, Cariati E, Giglio S
Eur J Med Genet 2017 Jul;60(7):365-368. Epub 2017 Apr 13 doi: 10.1016/j.ejmg.2017.04.007. PMID: 28414187
Narayanan DL, Bhavani GS, Girisha KM, Phadke SR
Indian Pediatr 2016 Aug 8;53(8):735-7. doi: 10.1007/s13312-016-0921-1. PMID: 27567651
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Hall CM, Elçioglu NH
Pediatr Radiol 2004 Jan;34(1):66-74. Epub 2003 Oct 18 doi: 10.1007/s00247-003-1063-x. PMID: 14566438

Therapy

Dai J, Kim OH, Cho TJ, Schmidt-Rimpler M, Tonoki H, Takikawa K, Haga N, Miyoshi K, Kitoh H, Yoo WJ, Choi IH, Song HR, Jin DK, Kim HT, Kamasaki H, Bianchi P, Grigelioniene G, Nampoothiri S, Minagawa M, Miyagawa SI, Fukao T, Marcelis C, Jansweijer MC, Hennekam RC, Bedeschi F, Mustonen A, Jiang Q, Ohashi H, Furuichi T, Unger S, Zabel B, Lausch E, Superti-Furga A, Nishimura G, Ikegawa S
J Med Genet 2010 Oct;47(10):704-9. Epub 2010 Jun 24 doi: 10.1136/jmg.2009.075358. PMID: 20577006

Prognosis

Theroux MC, Lopez M, Olszewsky PJ, DiCindio S, Arai L, Ditro C, Bober MB, Olla OO, Uejima T, West DW, Mackenzie WG
Paediatr Anaesth 2017 Jun;27(6):596-603. Epub 2017 Mar 21 doi: 10.1111/pan.13101. PMID: 28321993
Sitoula P, Mackenzie WG, Shah SA, Thacker M, Ditro C, Holmes L Jr, Campbell JW, Rogers KJ
Spine (Phila Pa 1976) 2014 Jul 1;39(15):E912-8. doi: 10.1097/BRS.0000000000000381. PMID: 24825152
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH
Am J Hum Genet 2009 Mar;84(3):307-15. Epub 2009 Feb 19 doi: 10.1016/j.ajhg.2009.01.021. PMID: 19232556Free PMC Article
Spranger J
Am J Med Genet 1989 Sep;34(1):96-104. doi: 10.1002/ajmg.1320340117. PMID: 2683785

Clinical prediction guides

Bauer JM, Ditro CP, Mackenzie WG
Spine Deform 2019 May;7(3):494-500. doi: 10.1016/j.jspd.2018.09.007. PMID: 31053321
Narayanan DL, Bhavani GS, Girisha KM, Phadke SR
Indian Pediatr 2016 Aug 8;53(8):735-7. doi: 10.1007/s13312-016-0921-1. PMID: 27567651
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH
Am J Hum Genet 2009 Mar;84(3):307-15. Epub 2009 Feb 19 doi: 10.1016/j.ajhg.2009.01.021. PMID: 19232556Free PMC Article
Geneviève D, Le Merrer M, Feingold J, Munnich A, Maroteaux P, Cormier-Daire V
Am J Med Genet A 2008 Apr 15;146A(8):992-6. doi: 10.1002/ajmg.a.32191. PMID: 18348257

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