Fibrodysplasia ossificans progressiva

General Information (adopted from Orphanet):

Synonyms, Signs: FOP
Myositis ossificans progressiva
Man of stone
Number of Symptoms 56
OrphanetNr: 337
OMIM Id: 135100
ICD-10: M61.1
UMLs: C0016037
MeSH: D009221
MedDRA: 10068715
Snomed: 82725007

Prevalence, inheritance and age of onset:

Prevalence: 0.05 of 100 000 [Orphanet]
Inheritance: Autosomal dominant
Not applicable
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic subcutaneous tissue disease
 -Rare genetic disease
Primary bone dysplasia with progressive ossification of skin, skeletal muscle, fascia, tendons and ligaments
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Subcutaneous tissue disease
 -Rare skin disease

Symptom Information: Sort by abundance 

1
(HPO:0000687) Widely spaced teeth 40 / 7739
2
(HPO:0000501) Glaucoma Occasional [Orphanet] 180 / 7739
3
(HPO:0000407) Sensorineural hearing impairment 524 / 7739
4
(HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
5
(HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
6
(HPO:0000365) Hearing impairment Frequent [Orphanet] 539 / 7739
7
(HPO:0000405) Conductive hearing impairment 164 / 7739
8
(HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
9
(HPO:0001249) Intellectual disability 6% [HPO:probinson] 1089 / 7739
10
(HPO:0003306) Spinal rigidity Very frequent [Orphanet] 30 / 7739
11
(HPO:0100249) Calcification of muscles Very frequent [Orphanet] 4 / 7739
12
(HPO:0003468) Abnormality of the vertebrae Very frequent [Orphanet] 77 / 7739
13
(HPO:0010054) Abnormality of the first metatarsal bone 1 / 7739
14
(HPO:0009778) Short thumb 50 / 7739
15
(HPO:0003016) Metaphyseal widening 41 / 7739
16
(HPO:0010034) Short 1st metacarpal 19 / 7739
17
(HPO:0011987) Ectopic ossification in muscle tissue 1 / 7739
18
(HPO:0002650) Scoliosis 705 / 7739
19
(HPO:0010109) Short hallux Very frequent [Orphanet] 27 / 7739
20
(HPO:0009601) Aplasia/Hypoplasia of the thumb Frequent [Orphanet] 80 / 7739
21
(HPO:0004209) Clinodactyly of the 5th finger Frequent [Orphanet] 288 / 7739
22
(HPO:0100240) Synostosis of joints Occasional [Orphanet] 11 / 7739
23
(HPO:0008449) Progressive cervical vertebral spine fusion 1 / 7739
24
(HPO:0006429) Broad femoral neck 18 / 7739
25
(HPO:0011989) Ectopic ossification in ligament tissue 2 / 7739
26
(HPO:0001387) Joint stiffness Very frequent [Orphanet] 322 / 7739
27
(HPO:0011988) Ectopic ossification in tendon tissue 1 / 7739
28
(HPO:0001822) Hallux valgus Occasional [Orphanet] 70 / 7739
29
(HPO:0001844) Abnormality of the hallux Very frequent [Orphanet] 3 / 7739
30
(HPO:0002763) Abnormal cartilage morphology Very frequent [Orphanet] 15 / 7739
31
(HPO:0004325) Decreased body weight Occasional [Orphanet] 492 / 7739
32
(HPO:0001596) Alopecia 162 / 7739
33
(HPO:0001006) Hypotrichosis Frequent [Orphanet] 219 / 7739
34
(HPO:0001031) Subcutaneous lipoma Very frequent [Orphanet] 112 / 7739
35
(HPO:0001903) Anemia Occasional [Orphanet] 289 / 7739
36
(HPO:0002878) Respiratory failure 57 / 7739
37
(HPO:0002091) Restrictive ventilatory defect 46 / 7739
38
(HPO:0002111) Restrictive deficit on pulmonary function testing 25 / 7739
39
(HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 410 / 7739
40
(OMIM) Joint immobility 1 / 7739
41
(HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
42
(HPO:0000006) Autosomal dominant inheritance 2518 / 7739
43
(OMIM) Monophalangism of first metatarsal 1 / 7739
44
(OMIM) Restricted arm mobility 1 / 7739
45
(OMIM) Painful swelling in aponeuroses 1 / 7739
46
(OMIM) Progressive ectopic ossification of tendons and ligaments 1 / 7739
47
(HPO:0004629) Small cervical vertebral bodies 2 / 7739
48
(OMIM) Jaw fixation 1 / 7739
49
(OMIM) Progressive ectopic ossification (neck, dorsal trunk, proximal limbs, sternocleidomastoid, masseters) 1 / 7739
50
(OMIM) Painful swelling in fasciae 1 / 7739
51
(OMIM) Reduction deficits of thumbs (in some patients) 1 / 7739
52
(OMIM) Flat, broad mandibular condyles 1 / 7739
53
(OMIM) Painful swellings in tendons 1 / 7739
54
(OMIM) Reduction deficits of halluces (in some patients) 1 / 7739
55
(OMIM) Proximal medial tibial osteochondromas 1 / 7739
56
(OMIM) Malformed first metatarsal 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, ...
Diagnosis OMIM Kaplan et al. (1993) reviewed histopathologic specimens from 11 patients, all children in whom the biopsy had been performed to exclude a malignant lesion. In no instance was the diagnosis of FOP considered before the biopsy. In 6 ...
Clinical Description OMIM Fibrodysplasia ossificans progressiva is a rare disorder characterized by physical handicap due to intermittently progressive ectopic ossification and malformed big toes which are often monophalangic. Occasional features include short thumbs, fifth finger clinodactyly, malformed cervical vertebrae, short broad ...
Molecular genetics OMIM Shore et al. (2006) conducted a genomewide linkage analysis using a subset of 5 families with the most stringent and unambiguous features of FOP, congenital malformation of the great toes and progressive heterotopic ossification in characteristic anatomic patterns, ...