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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
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Progressive diaphyseal dysplasia (318761000119105); 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)
 
Gene (location): TGFB1 (19q13.2)
OMIM®: 131300
HPO: HP:0100252

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, severe limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as 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 GHR
Camurati-Engelmann disease is a condition that mainly affects the bones. People with this disease have increased bone density, particularly affecting the long bones of the arms and legs. In some cases, the skull and hip bones are also affected. The thickened bones can lead to pain in the arms and legs, a waddling walk, muscle weakness, and extreme tiredness. An increase in the density of the skull results in increased pressure on the brain and can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis. The added pressure that thickened bones put on the muscular and skeletal systems can cause abnormal curvature of the spine (scoliosis), joint deformities (contractures), knock knees, and flat feet (pes planus). Other features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, and delayed puberty.The age at which affected individuals first experience symptoms varies greatly; however, most people with this condition develop pain or weakness by adolescence. In some instances, people have the gene mutation that causes Camurati-Engelmann disease but never develop the characteristic features of this condition.  https://ghr.nlm.nih.gov/condition/camurati-engelmann-disease

Clinical features

Pain in limb
MedGen UID:
10540
Concept ID:
C0030196
Sign or Symptom
Chronic pain in the limbs with no clear focal etiology.
delayed male puberty
MedGen UID:
893076
Concept ID:
C2367046
Disease or Syndrome
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Proptosis
MedGen UID:
350667
Concept ID:
C1862425
Finding
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Poor appetite
MedGen UID:
68562
Concept ID:
C0232462
Sign or Symptom
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Almost everyone has had a headache. Headache is the most common form of pain. It's a major reason people miss days at work or school or visit the doctor. The most common type of headache is a tension headache. Tension headaches are due to tight muscles in your shoulders, neck, scalp and jaw. They are often related to stress, depression or anxiety. You are more likely to get tension headaches if you work too much, don't get enough sleep, miss meals, or use alcohol. Other common types of headaches include migraines, cluster headaches, and sinus headaches. Most people can feel much better by making lifestyle changes, learning ways to relax and taking pain relievers. Not all headaches require a doctor's attention. But sometimes headaches warn of a more serious disorder. Let your health care provider know if you have sudden, severe headaches. Get medical help right away if you have a headache after a blow to your head, or if you have a headache along with a stiff neck, fever, confusion, loss of consciousness, or pain in the eye or ear. NIH: National Institute of Neurological Disorders and Stroke.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Optic nerve compression
MedGen UID:
78765
Concept ID:
C0271344
Disease or Syndrome
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Denervation atrophy of muscle
MedGen UID:
78748
Concept ID:
C0270948
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Diaphyseal dysplasia
MedGen UID:
4268
Concept ID:
C0011989
Finding
Camurati-Engelmann disease (CED) is characterized by hyperostosis of the long bones and the skull, proximal muscle weakness, severe limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life.
Pain in limb
MedGen UID:
10540
Concept ID:
C0030196
Sign or Symptom
Chronic pain in the limbs with no clear focal etiology.
Sclerosis of skull base
MedGen UID:
377095
Concept ID:
C1851714
Finding
Increased bone density of the skull base without significant changes in bony contour.
Cortical thickening of long bone diaphyses
MedGen UID:
425785
Concept ID:
CN005115
Finding
Abnormal thickening of the cortex of the diaphyseal region of long bones.
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

Conditions with this feature

Diaphyseal dysplasia
MedGen UID:
4268
Concept ID:
C0011989
Finding
Camurati-Engelmann disease (CED) is characterized by hyperostosis of the long bones and the skull, proximal muscle weakness, severe limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life.
Osteopetrosis with renal tubular acidosis
MedGen UID:
91042
Concept ID:
C0345407
Disease or Syndrome
Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder.
Craniodiaphyseal dysplasia
MedGen UID:
96080
Concept ID:
C0410539
Congenital Abnormality
Ribbing disease
MedGen UID:
321923
Concept ID:
C1832273
Disease or Syndrome
Osteopetrosis autosomal recessive 2
MedGen UID:
342420
Concept ID:
C1850126
Disease or Syndrome
Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder.
Distal osteosclerosis
MedGen UID:
338863
Concept ID:
C1852063
Disease or Syndrome
Ghosal syndrome
MedGen UID:
344739
Concept ID:
C1856465
Congenital Abnormality
Ghosal hematodiaphyseal dysplasia is a rare inherited condition characterized by abnormally thick bones and a shortage of red blood cells (anemia). Signs and symptoms of the condition become apparent in early childhood.In affected individuals, the long bones in the arms and legs are unusually dense and wide. The bone changes specifically affect the shafts of the long bones, called diaphyses, and areas near the ends of the bones called metaphyses. The bone abnormalities can lead to bowing of the legs and difficulty walking.Ghosal hematodiaphyseal dysplasia also causes scarring (fibrosis) of the bone marrow, which is the spongy tissue inside long bones where blood cells are formed. The abnormal bone marrow cannot produce enough red blood cells, which leads to anemia.Signs and symptoms of anemia that have been reported in people with Ghosal hematodiaphyseal dysplasia include extremely pale skin (pallor) and excessive tiredness (fatigue).
Craniodiaphyseal dysplasia, autosomal dominant
MedGen UID:
382678
Concept ID:
C2675746
Disease or Syndrome
Craniodiaphyseal dysplasia is a severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. Progressive bony encroachment upon cranial foramina leads to severe neurologic impairment in childhood (summary by Brueton and Winter, 1990). The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine facies), and the bone deposition results in progressive stenosis of craniofacial foramina (summary by Kim et al., 2011).
Congenital disorder of glycosylation type 2k
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).

Recent clinical studies

Etiology

Bhadada SK, Sridhar S, Steenackers E, Dhiman V, Mortier G, Bhansali A, Van Hul W
Calcif Tissue Int 2014 Feb;94(2):240-7. Epub 2013 Oct 24 doi: 10.1007/s00223-013-9804-9. PMID: 24154985
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
Inaoka T, Shuke N, Sato J, Ishikawa Y, Takahashi K, Aburano T, Makita Y
Clin Nucl Med 2001 Aug;26(8):680-2. PMID: 11452173
Ghosal SP, Mukherjee AK, Mukherjee D, Ghosh AK
J Pediatr 1988 Jul;113(1 Pt 1):49-57. PMID: 3385529
Kaftori JK, Kleinhaus U, Naveh Y
Radiology 1987 Sep;164(3):777-82. doi: 10.1148/radiology.164.3.3615880. PMID: 3615880

Diagnosis

Bhadada SK, Sridhar S, Steenackers E, Dhiman V, Mortier G, Bhansali A, Van Hul W
Calcif Tissue Int 2014 Feb;94(2):240-7. Epub 2013 Oct 24 doi: 10.1007/s00223-013-9804-9. PMID: 24154985
Park SJ, Yoon CS, Park HW, Choi JR, Chung JS, Lee KA
J Korean Med Sci 2009 Aug;24(4):737-40. Epub 2009 Jul 30 doi: 10.3346/jkms.2009.24.4.737. PMID: 19654961Free PMC Article
Mondal RK, Karmakar B, Chandra PK, Mukherjee K
Indian J Pediatr 2007 Mar;74(3):291-3. PMID: 17401271
Simsek S, Janssens K, Kwee ML, Van Hul W, Veenstra J, Netelenbos JC
Osteoporos Int 2005 Sep;16(9):1167-70. Epub 2005 Jun 16 doi: 10.1007/s00198-005-1896-2. PMID: 15959620
Alebouyeh M, Vossough P, Tabarrok F
Pediatr Hematol Oncol 2003 Jul-Aug;20(5):409-15. PMID: 12775540

Therapy

Wallace SE, Lachman RS, Mekikian PB, Bui KK, Wilcox WR
Am J Med Genet A 2004 Sep 1;129A(3):235-47. doi: 10.1002/ajmg.a.30148. PMID: 15326622
Alebouyeh M, Vossough P, Tabarrok F
Pediatr Hematol Oncol 2003 Jul-Aug;20(5):409-15. PMID: 12775540
Inaoka T, Shuke N, Sato J, Ishikawa Y, Takahashi K, Aburano T, Makita Y
Clin Nucl Med 2001 Aug;26(8):680-2. PMID: 11452173
Baş F, Darendeliler F, Petorak I, Sadikoğlu B, Bilir A, Bundak R, Saka N, Günöz H
J Paediatr Child Health 1999 Aug;35(4):401-5. PMID: 10457303
Saraiva JM
Am J Med Genet 1997 Aug 22;71(3):348-52. PMID: 9268107

Prognosis

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
Inaoka T, Shuke N, Sato J, Ishikawa Y, Takahashi K, Aburano T, Makita Y
Clin Nucl Med 2001 Aug;26(8):680-2. PMID: 11452173
Ghosal SP, Mukherjee AK, Mukherjee D, Ghosh AK
J Pediatr 1988 Jul;113(1 Pt 1):49-57. 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

Bondestam J, Mäyränpää MK, Ikegawa S, Marttinen E, Kröger H, Mäkitie O
Clin Rheumatol 2007 Oct;26(10):1773-7. Epub 2007 Jan 6 doi: 10.1007/s10067-006-0511-z. PMID: 17206397
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. 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. PMID: 10631145Free PMC Article
Naveh Y, Alon U, Kaftori JK, Berant M
Pediatrics 1985 Feb;75(2):321-3. PMID: 3969334

Recent systematic reviews

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

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