Frontometaphyseal dysplasia

General Information (adopted from Orphanet):

Synonyms, Signs: FMD
Number of Symptoms 81
OrphanetNr: 1826
OMIM Id: 305620
ICD-10: Q78.5
UMLs: C0265293
MeSH: C538064
MedDRA:
Snomed: 62803002

Prevalence, inheritance and age of onset:

Prevalence: < 30 cases [Orphanet]
Inheritance: X-linked dominant
[Orphanet]
Age of onset: Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Fronto-otopalatodigital syndrome
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Genetic multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare developmental defect during embryogenesis
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000071) Ureteral stenosis Occasional [Orphanet] 9 / 7739
2
 (HPO:0000072) Hydroureter Occasional [Orphanet] 146 / 7739
3
 (HPO:0000126) Hydronephrosis 119 / 7739
4
 (HPO:0000795) Abnormality of the urethra Occasional [Orphanet] 38 / 7739
5
 (HPO:0000218) High palate 356 / 7739
6
 (HPO:0000277) Abnormality of the mandible Very frequent [Orphanet] 394 / 7739
7
 (HPO:0000684) Delayed eruption of teeth 117 / 7739
8
 (HPO:0002705) High, narrow palate Frequent [Orphanet] 308 / 7739
9
 (HPO:0000689) Dental malocclusion 114 / 7739
10
 (HPO:0009119) Aplasia/Hypoplasia of the frontal sinuses Very frequent [Orphanet] 6 / 7739
11
 (HPO:0006335) Persistence of primary teeth 12 / 7739
12
 (HPO:0000307) Pointed chin 45 / 7739
13
 (HPO:0001363) Craniosynostosis Occasional [Orphanet] 132 / 7739
14
 (HPO:0000336) Prominent supraorbital ridges Very frequent [Orphanet] 45 / 7739
15
 (HPO:0000331) Short chin 33 / 7739
16
 (HPO:0000316) Hypertelorism Very frequent [Orphanet] 644 / 7739
17
 (HPO:0006482) Abnormality of dental morphology Very frequent [Orphanet] 81 / 7739
18
 (HPO:0002700) Large foramen magnum 6 / 7739
19
 (HPO:0001592) Selective tooth agenesis 16 / 7739
20
 (HPO:0004437) Cranial hyperostosis Very frequent [Orphanet] 55 / 7739
21
 (HPO:0000494) Downslanted palpebral fissures Very frequent [Orphanet] 328 / 7739
22
 (HPO:0003779) Antegonial notching of mandible 2 / 7739
23
 (HPO:0000431) Wide nasal bridge 290 / 7739
24
 (HPO:0000280) Coarse facial features 189 / 7739
25
 (HPO:0000405) Conductive hearing impairment Frequent [Orphanet] 164 / 7739
26
 (HPO:0000407) Sensorineural hearing impairment Frequent [Orphanet] 524 / 7739
27
 (HPO:0001249) Intellectual disability 1089 / 7739
28
 (HPO:0006665) Coat hanger sign of ribs 1 / 7739
29
 (HPO:0003691) Scapular winging 51 / 7739
30
 (HPO:0004608) Anteriorly placed odontoid process 1 / 7739
31
 (HPO:0006155) Long phalanx of finger 1 / 7739
32
 (HPO:0009768) Broad phalanges of the hand 3 / 7739
33
 (HPO:0100490) Camptodactyly of finger Very frequent [Orphanet] 212 / 7739
34
 (HPO:0009601) Aplasia/Hypoplasia of the thumb Frequent [Orphanet] 80 / 7739
35
 (HPO:0002987) Elbow flexion contracture 64 / 7739
36
 (HPO:0000944) Abnormality of the metaphyses Very frequent [Orphanet] 141 / 7739
37
 (HPO:0002949) Fused cervical vertebrae 13 / 7739
38
 (HPO:0001166) Arachnodactyly 62 / 7739
39
 (HPO:0001239) Wrist flexion contracture 13 / 7739
40
 (HPO:0002650) Scoliosis Frequent [Orphanet] 705 / 7739
41
 (HPO:0000940) Abnormal diaphysis morphology Very frequent [Orphanet] 41 / 7739
42
 (HPO:0009465) Ulnar deviation of finger Frequent [Orphanet] 48 / 7739
43
 (HPO:0006466) Ankle contracture 17 / 7739
44
 (HPO:0002857) Genu valgum 144 / 7739
45
 (HPO:0005048) Synostosis of carpal bones Frequent [Orphanet] 39 / 7739
46
 (HPO:0003312) Abnormal form of the vertebral bodies Frequent [Orphanet] 172 / 7739
47
 (HPO:0001387) Joint stiffness Very frequent [Orphanet] 322 / 7739
48
 (HPO:0011302) Long palm Frequent [Orphanet] 70 / 7739
49
 (HPO:0001833) Long foot 33 / 7739
50
 (HPO:0005616) Accelerated skeletal maturation Frequent [Orphanet] 46 / 7739
51
 (HPO:0006380) Knee flexion contracture 56 / 7739
52
 (HPO:0006207) Partial fusion of carpals 1 / 7739
53
 (HPO:0008097) Partial fusion of tarsals 1 / 7739
54
 (HPO:0003042) Elbow dislocation Frequent [Orphanet] 89 / 7739
55
 (HPO:0002673) Coxa valga 57 / 7739
56
 (HPO:0006487) Bowing of the long bones Very frequent [Orphanet] 95 / 7739
57
 (HPO:0006440) Increased density of long bone diaphyses 1 / 7739
58
 (HPO:0001007) Hirsutism 91 / 7739
59
 (HPO:0001634) Mitral valve prolapse 69 / 7739
60
 (HPO:0006695) Atrioventricular canal defect Occasional [Orphanet] 27 / 7739
61
 (HPO:0001648) Cor pulmonale 16 / 7739
62
 (HPO:0001602) Laryngeal stenosis Occasional [Orphanet] 21 / 7739
63
 (HPO:0002777) Tracheal stenosis Occasional [Orphanet] 35 / 7739
64
 (HPO:0010307) Stridor 19 / 7739
65
 (HPO:0003202) Skeletal muscle atrophy Frequent [Orphanet] 281 / 7739
66
 (HPO:0003700) Generalized amyotrophy 39 / 7739
67
 (HPO:0100295) Muscle fiber atrophy 22 / 7739
68
 (OMIM) Erlenmeyer-flask appearance of femur and tibia 1 / 7739
69
 (OMIM) Hirsutism of buttocks and thighs 1 / 7739
70
 (OMIM) Subglottic tracheal narrowing 1 / 7739
71
 (OMIM) Progressive mixed conductive and sensorineural hearing loss 1 / 7739
72
 (OMIM) Finger and wrist contractures 1 / 7739
73
 (OMIM) Irregular rib contours 1 / 7739
74
 (OMIM) Wide and elongated phalanges 1 / 7739
75
 (OMIM) Wide interpedicular distance 1 / 7739
76
 (OMIM) Hypoplastic condyloid process 1 / 7739
77
 (OMIM) Incomplete sinus development 1 / 7739
78
 (HPO:0001419) X-linked recessive inheritance 189 / 7739
79
 (OMIM) Large feet 12 / 7739
80
 (OMIM) Flared pelvis 1 / 7739
81
 (OMIM) Congenital stridor 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Frontometaphyseal dysplasia is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include otopalatodigital syndrome-1 (OPD1; 311300), otopalatodigital syndrome-2 (OPD2; 304120), and Melnick-Needles syndrome (MNS; 309350), constitute a phenotypic spectrum. At the ...
Clinical Description OMIM Gorlin and Cohen (1969) described a male patient with extraordinarily marked frontal hyperostosis giving great prominence to the supraciliary ridges, underdeveloped mandible, cryptorchidism, subluxated radial heads, and metaphyseal dysplasia resembling that in Pyle disease (metaphyseal dysplasia). This may ...
Molecular genetics OMIM Robertson et al. (2003) demonstrated gain-of-function mutations in the filamin A gene in patients with frontometaphyseal dysplasia; see, e.g., 300017.0011 (D1159A) and 300017.0015 (S1186L).

Giuliano et al. (2005) identified the S1186L mutation in the FLNA gene ...