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Diaphyseal dysplasia(CAEND)

MedGen UID:
4268
Concept ID:
C0011989
Disease or Syndrome; Finding
Synonyms: CAEND; Camurati-Engelmann Disease; Diaphyseal dysplasia 1, progressive; Engelmann disease; Progressive diaphyseal dysplasia
SNOMED CT: Progressive diaphyseal dysplasia (34643004); Engelmann syndrome (34643004); Engelman's disease (34643004); Camurati-Engelmann syndrome (34643004); Diaphyseal dysplasia (34643004); Engelmann's disease (34643004); Diaphyseal sclerosis (34643004); Osteopathia hyperostotica multiplex infantis (34643004)
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.
 
Gene (location): TGFB1 (19q13.2)
 
HPO: HP:0100252
Monarch Initiative: MONDO:0007542
OMIM®: 131300
Orphanet: ORPHA1328

Disease characteristics

Excerpted from the GeneReview: Camurati-Engelmann Disease
Camurati-Engelmann disease (CED) is characterized by hyperostosis of the long bones and the skull, proximal muscle weakness, limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as macrocephaly, frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life. [from GeneReviews]
Authors:
Stephanie E Wallace  |  William R Wilcox   view full author information

Additional descriptions

From OMIM
Camurati-Engelmann disease is a rare autosomal dominant type of bone bone dysplasia. The hallmark of the disorder is the cortical thickening of the diaphyses of the long bones. Hyperostosis is bilateral and symmetrical and usually starts at the diaphyses of the femora and tibiae, expanding to the fibulae, humeri, ulnae, and radii. As the disease progresses, the metaphyses may be affected as well, but the epiphyses are spared. Sclerotic changes at the skull base may be present. The onset of the disease is usually during childhood and almost always before the age of 30. Most patients present with limb pain, muscular weakness, a waddling gait, and easy fatigability. Systemic manifestations such as anemia, leukopenia, and hepatosplenomegaly occur occasionally (summary by Janssens et al., 2006).  http://www.omim.org/entry/131300
From MedlinePlus Genetics
Camurati-Engelmann disease is a skeletal condition that is characterized by abnormally thick bones (hyperostosis) in the arms, legs, and skull.

The thick limb bones can lead to bone pain and muscle weakness in the arms and legs and cause individuals with Camurati-Engelmann disease to tire quickly. Bone pain ranges from mild to severe and can increase with stress, activity, or cold weather. Leg weakness can make it difficult to stand up from a seated position and some affected individuals develop a waddling or unsteady walk. Additional limb abnormalities include joint deformities (contractures), knock knees, and flat feet (pes planus). Swelling and redness (erythema) of the limbs and an abnormal curvature of the spine can also occur.

Individuals with Camurati-Engelmann disease may have an unusually thick skull, which can lead to an abnormally large head (macrocephaly) and lower jaw (mandible), a prominent forehead (frontal bossing), and bulging eyes with shallow eye sockets (ocular proptosis). These changes to the head and face become more prominent with age and are most noticeable in affected adults. In about a quarter of individuals with Camurati-Engelmann disease, the thickened skull increases pressure on the brain or compresses the spinal cord, which can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis.

The degree of hyperostosis varies among individuals with Camurati-Engelmann disease as does the age at which they experience their first symptoms.

Other, rare features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, delayed teething (dentition), frequent cavities, delayed puberty, a shortage of red blood cells (anemia), an enlarged liver and spleen (hepatosplenomegaly), thinning of the skin, and excessively sweaty (hyperhidrotic) hands and feet.  https://medlineplus.gov/genetics/condition/camurati-engelmann-disease

Clinical features

From HPO
Lower limb pain
MedGen UID:
6033
Concept ID:
C0023222
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the leg.
Limb pain
MedGen UID:
10540
Concept ID:
C0030196
Sign or Symptom
Chronic pain in the limbs with no clear focal etiology.
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.
Slender build
MedGen UID:
376828
Concept ID:
C1850573
Finding
Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.
Poor appetite
MedGen UID:
68562
Concept ID:
C0232462
Sign or Symptom
A reduced desire to eat.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Optic nerve compression
MedGen UID:
78765
Concept ID:
C0271344
Disease or Syndrome
Cranial nerve compression
MedGen UID:
141743
Concept ID:
C0521670
Disease or Syndrome
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Narrowing of medullary canal
MedGen UID:
377067
Concept ID:
C1851612
Finding
A reduction in diameter and volume of the central cavity of bone where red or yellow bone marrow is located.
Sclerosis of skull base
MedGen UID:
377095
Concept ID:
C1851714
Finding
Increased bone density of the skull base without significant changes in bony contour.
Reduced subcutaneous adipose tissue
MedGen UID:
387876
Concept ID:
C1857657
Finding
A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.
Cortical thickening of long bone diaphyses
MedGen UID:
870679
Concept ID:
C4025133
Anatomical Abnormality
Abnormal thickening of the cortex of the diaphyseal region of long bones.
Diaphyseal sclerosis
MedGen UID:
1631208
Concept ID:
C4551853
Finding
An elevation in bone density in one or more diaphyses. Sclerosis is normally detected on a radiograph as an area of increased opacity.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
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  
  • CROGVDiaphyseal dysplasia
Follow this link to review classifications for Diaphyseal dysplasia in Orphanet.

Conditions with this feature

Ghosal hematodiaphyseal dysplasia
MedGen UID:
344739
Concept ID:
C1856465
Congenital Abnormality
Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia (summary by Genevieve et al., 2008).
TMEM165-congenital disorder of glycosylation
MedGen UID:
766485
Concept ID:
C3553571
Disease or Syndrome
CDG2K is an autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern (summary by Foulquier et al., 2012). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066).
Craniotubular dysplasia, Ikegawa type
MedGen UID:
1806238
Concept ID:
C5575335
Disease or Syndrome
Craniotubular dysplasia, Ikegawa type (CTDI) is characterized by childhood-onset short stature in association with macrocephaly, dolichocephaly, or prominent forehead. Radiography shows hyperostosis of the calvaria and skull base, with metadiaphyseal undermodeling of the long tubular bones and mild shortening and diaphyseal broadening of the short tubular bones. Affected individuals experience progressive vision loss in the first decade of life due to optic nerve compression, and deafness may develop in the second decade of life (Guo et al., 2021).

Professional guidelines

PubMed

Allen DT, Saunders AM, Northway WH Jr, Williams GF, Schafer IA
Pediatrics 1970 Oct;46(4):523-31. PMID: 5503688

Recent clinical studies

Etiology

Dhar SU, Taylor T, Trinh C, Sutton VR
Am J Med Genet A 2010 Sep;152A(9):2335-8. doi: 10.1002/ajmg.a.33582. PMID: 20684007
Faden MA, Krakow D, Ezgu F, Rimoin DL, Lachman RS
Am J Med Genet A 2009 Jun;149A(6):1334-45. doi: 10.1002/ajmg.a.32253. PMID: 19444897Free PMC Article
Vanhoenacker FM, De Beuckeleer LH, Van Hul W, Balemans W, Tan GJ, Hill SC, De Schepper AM
Eur Radiol 2000;10(9):1423-33. doi: 10.1007/s003300000495. PMID: 10997431
Greenspan A
Skeletal Radiol 1991;20(8):561-83. doi: 10.1007/BF01106087. PMID: 1776023
Kaftori JK, Kleinhaus U, Naveh Y
Radiology 1987 Sep;164(3):777-82. doi: 10.1148/radiology.164.3.3615880. PMID: 3615880

Diagnosis

B S, Kotha JP
J Assoc Physicians India 2023 Jan;71(1):1. PMID: 37116016
Van Hul W, Boudin E, Vanhoenacker FM, Mortier G
Calcif Tissue Int 2019 May;104(5):554-560. Epub 2019 Feb 5 doi: 10.1007/s00223-019-00532-1. PMID: 30721323
Yap FY, Skalski MR, Patel DB, Schein AJ, White EA, Tomasian A, Masih S, Matcuk GR Jr
Radiographics 2017 Jan-Feb;37(1):157-195. Epub 2016 Dec 9 doi: 10.1148/rg.2017160052. PMID: 27935768
Boulet C, Madani H, Lenchik L, Vanhoenacker F, Amalnath DS, de Mey J, De Maeseneer M
Br J Radiol 2016 Jun;89(1062):20150349. Epub 2016 Feb 22 doi: 10.1259/bjr.20150349. PMID: 26898950Free PMC Article
Levine SM, Lambiase RE, Petchprapa CN
Radiographics 2003 Jan-Feb;23(1):157-77. doi: 10.1148/rg.231015088. PMID: 12533651

Therapy

Cui L, Li Q, Guan W, Yu W, Li X, Xia W, Jiang Y
Front Endocrinol (Lausanne) 2022;13:882144. Epub 2022 Jun 17 doi: 10.3389/fendo.2022.882144. PMID: 35784539Free PMC Article
Van Hul W, Boudin E, Vanhoenacker FM, Mortier G
Calcif Tissue Int 2019 May;104(5):554-560. Epub 2019 Feb 5 doi: 10.1007/s00223-019-00532-1. PMID: 30721323
Inaoka T, Shuke N, Sato J, Ishikawa Y, Takahashi K, Aburano T, Makita Y
Clin Nucl Med 2001 Aug;26(8):680-2. doi: 10.1097/00003072-200108000-00003. PMID: 11452173
De Vits A, Keymeulen B, Bossuyt A, Somers G, Verbruggen LA
Clin Nucl Med 1994 Feb;19(2):104-7. doi: 10.1097/00003072-199402000-00005. PMID: 8187392
Naveh Y, Alon U, Kaftori JK, Berant M
Pediatrics 1985 Feb;75(2):321-3. PMID: 3969334

Prognosis

Yap FY, Skalski MR, Patel DB, Schein AJ, White EA, Tomasian A, Masih S, Matcuk GR Jr
Radiographics 2017 Jan-Feb;37(1):157-195. Epub 2016 Dec 9 doi: 10.1148/rg.2017160052. PMID: 27935768
Dhar SU, Taylor T, Trinh C, Sutton VR
Am J Med Genet A 2010 Sep;152A(9):2335-8. doi: 10.1002/ajmg.a.33582. PMID: 20684007
Ghosal SP, Mukherjee AK, Mukherjee D, Ghosh AK
J Pediatr 1988 Jul;113(1 Pt 1):49-57. doi: 10.1016/s0022-3476(88)80527-4. PMID: 3385529
Kaftori JK, Kleinhaus U, Naveh Y
Radiology 1987 Sep;164(3):777-82. doi: 10.1148/radiology.164.3.3615880. PMID: 3615880
Naveh Y, Alon U, Kaftori JK, Berant M
Pediatrics 1985 Feb;75(2):321-3. PMID: 3969334

Clinical prediction guides

Cui L, Li Q, Guan W, Yu W, Li X, Xia W, Jiang Y
Front Endocrinol (Lausanne) 2022;13:882144. Epub 2022 Jun 17 doi: 10.3389/fendo.2022.882144. PMID: 35784539Free PMC Article
Li Q, Zhao Z, Wu B, Pang Q, Cui L, Zhang L, Jiang Y, Wang O, Li M, Xing X, Hu Y, Yu W, Meng X, Jiajue R, Xia W
J Bone Miner Res 2022 Jan;37(1):78-86. Epub 2021 Sep 28 doi: 10.1002/jbmr.4436. PMID: 34490910
Yonezawa H, Hayashi K, Yamamoto N, Takeuchi A, Tada K, Miwa S, Igarashi K, Kimura H, Aoki Y, Morinaga S, Araki Y, Asano Y, Sakurakichi K, Ikeda H, Nojima T, Tsuchiya H
Calcif Tissue Int 2021 Jun;108(6):819-824. Epub 2021 Feb 8 doi: 10.1007/s00223-021-00813-8. PMID: 33555353
Janssens K, Gershoni-Baruch R, Van Hul E, Brik R, Guañabens N, Migone N, Verbruggen LA, Ralston SH, Bonduelle M, Van Maldergem L, Vanhoenacker F, Van Hul W
J Med Genet 2000 Apr;37(4):245-9. doi: 10.1136/jmg.37.4.245. PMID: 10745041Free PMC Article
Ghadami M, Makita Y, Yoshida K, Nishimura G, Fukushima Y, Wakui K, Ikegawa S, Yamada K, Kondo S, Niikawa N, Tomita Ha
Am J Hum Genet 2000 Jan;66(1):143-7. doi: 10.1086/302728. PMID: 10631145Free PMC Article

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