Table 1

 Overview of clinical, radiological, scintigraphic, and molecular data on patients from the 24 families

Family 1Family 2Family 3Family 4Family 5
(Belgium)(Iraq)(UK)(Italy)(Belgium)
Mutation (DNA)673T→C653G→A652C→T28_36dup241T→C
Mutation (protein)C225RR218HR218CL10-L12dupY81H
Number of patients35323
Clinical symptoms3/34/52/32/21/3
    Pain in extremities2/34/52/30/21/3
    Easy fatigability0/33/52/30/21/3
    Muscle weakness0/32/52/30/21/3
    Waddling gait1/33/51/30/21/3
    Hearing loss0/32/50/32/20/3
    Reduced subcutaneous fat1/32/50/32/21/3
    OtherHyperthermia (1/3)Hepatosplenomegaly (1/3)ESR and CRP↑ (2/3)–Small stature (1/3)
Cranial nerve compression (1/3)
Small stature (2/3)
Headache (1/3)
Radiological abnormalities3/35/53/32/21/3
    Cortical thickening diaphyses3/35/53/32/21/3
    Sclerosis of skull1/32/5ND2/20/3
    Other––Spine osteoporotic (2/3)Spine, pelvis (1/2)–
Coxa valga (2/3)
Increased BMDNDND+ (hip) (2/3)2/2ND
− (spine) (2/3)
Scintigraphic abnormalitiesND4/4ND1/11/1
TreatmentGC (1/3)GC (1/5)GC (2/3)Calcitonin (1/2)GC (1/3)
NSAIDs (1/3)NSAIDs (2/3)BP (2/2)NSAIDs (1/3)
Analgesics (2/3)Analgesics (1/3)
BP (2/3)
Tibial osteotomy (1/3)
Femoral osteotomy (1/3)
Family 6Family 7Family 8Family 9Family 10
(Belgium)(Italy)(Germany)(UK)(Tonga-Oceania)
Mutation (DNA)241T→C653G→A653G→A653G→A653G→A
Mutation (protein)Y81HR218HR218HR218HR218H
Number of patients62322
Clinical symptoms3/62/21/31/21/2
    Pain in extremities2/61/21/31/20/2
    Easy fatigability1/61/21/30/20/2
    Muscle weakness1/61/21/30/20/2
    Waddling gait2/62/21/30/20/2
    Hearing loss0/60/20/30/21/2
    Reduced subcutaneous fat0/61/20/30/20/2
    Other––––Proptosis (1/2)
Radiological abnormalities4/62/21/12/22/2
    Cortical thickening diaphyses4/62/21/12/22/2
    Sclerosis of skull1/20/2NDND1/1
    OtherPelvis (1/2)––ND–
Increased BMDNDNDNDND1/1
Scintigraphic abnormalities1/6ND1/1ND1/1
TreatmentGC (1/6)–PenicillinTreated with vitamin D for presumed rickets (1/2)Orbital decompression (1/1)
BP (1/6)Gold salts
NSAIDs
Family 11Family 12Family 13Family 14Family 15*
(Morocco)(Belgium)(Spain)(Germany)(Israel)
Mutation (DNA)463C→T673T→C652C→T664C→G652C→T
Mutation (protein)R156CC225RR218CH222DR218C
Number of patients234116
Clinical symptoms2/22/34/41/110/16
    Pain in extremities2/22/32/41/18/8
    Easy fatigability1/21/30/41/1ND
    Muscle weakness0/21/34/41/14/8
    Waddling gait1/21/31/41/16/8
    Hearing loss0/20/30/40/10/8
    Reduced subcutaneous fatObese (2/2)Obese (1/3)0/41/1ND
    OtherESR and CRP↑ (1/2)–Vision ↓ (1/4)Delayed pubertyInability to run quickly (3/8)
Mild splenomegaly (2/4)Small stature
Recurrent facial paralysis (1/4)
Hypertension (1/4)
Radiological abnormalities2/23/34/41/111/11
    Cortical thickening diaphyses2/23/34/41/111/11
    Sclerosis of skull0/20/34/40/1ND
    OtherEnlarged mandible (1/2)Kyphoscoliosis (1/3)Pelvis (3/4)Genu valgumND
Coxa valga (1/3)Spine (1/4)Pes valgus
Vertebrae (1/4)Coxa valga
Increased BMDNDNDNDNDND
Scintigraphic abnormalities2/21/24/4NDND
TreatmentAnalgesics (2/2)NSAIDs (2/3)GC (1/4)–?
GC (2/2)
Family 16†Family 17‡Family 18‡Family 19‡Family 20‡
(Japan)(Portugal)(France)(Belgium)(France)
Mutation (DNA)673T→C653G→A652C→T673T→C673T→C
Mutation (protein)C225RR218HR218CC225RC225R
Number of patients1212233
Clinical symptoms10/1210/122/22/32/3
    Pain in extremities10/1210/122/22/32/3
    Easy fatigabilityND8/121/22/32/3
    Muscle weakness7/127/121/22/32/3
    Waddling gait5/127/121/11/32/3
    Hearing loss3/12NDNDNDND
    Reduced subcutaneous fatNDNDNDNDND
    OtherMarfanoid habitus (3/12)Headache (2/12) Poor appetite (2/12)Poor appetite (1/2)Headache (3/3) Poor appetite (1/3)
Facial nerve palsy (1/12)Delayed puberty (?)
Delayed puberty (1/1)
Radiological abnormalities12/1210/10ND3/33/3
    Cortical thickening diaphyses12/1210/10ND3/33/3
    Sclerosis of skull3/129/11NDND1/2
    OtherNDNDNDNDND
Increased BMDND8/102/23/33/3
Scintigraphic abnormalities1/1NDNDNDND
Treatment?GC (1/12)???
Family 21‡Family 22‡Family 23‡Family 24§
(Australia)(France)(France)(USA)Summary
*This family has been described by Janssens et al.12
†This family has been described by Makita et al.9
‡These families have been described by Campos-Xavier et al.10
§This family has been described by Wallace et al.11
?, Data not available; –, data absent; ↑, increased; ↓, decreased.
BMD, bone mineral density; BP, bisphophonates; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; GC, glucocorticoids; ND, not determined; NSAIDs, non-steroidal anti-inflammatory drugs.
Mutation (DNA)673T→C652C→T652C→T653G→A
Mutation (protein)C225RR218CR218CR218H
Number of patients2126 100
Clinical symptoms2/21/12/24/6 74/100 (74%)
    Pain in extremities2/21/12/23/6 63/92 (68%)
    Easy fatigability2/21/11/23/6 32/72 (44%)
    Muscle weakness1/21/11/24/6 36/92 (39%)
    Waddling gait1/21/11/24/6 44/92 (48%)
    Hearing lossNDNDND2/6 10/67 (15%)
    Reduced subcutaneous fatNDNDND2/6 10/47 (21%)–3/47 (6%) obese
    OtherHeadache (2/2) Poor appetite (2/2)Poor appetiteHeadache (1/2) Poor appetite (1/2)Vertigo, tinnitus, balance problems (2/6)
Delayed puberty (1/6)
Poor appetite (1/6)
Facial paralysis (1/6)
Radiological abnormalities2/21/12/23/4 82/87 (94%)
    Cortical thickening diaphyses2/21/12/23/4 82/87 (94%)
    Sclerosis of skull2/21/12/23/4 32/59 (54%)
    OtherNDNDNDEnlarged mandible (1/6) Pelvis 5/8 (63%)
Genu valgum (3/6)
Pes planus (3/6)
Increased BMD2/21/12/2ND 26/29 (90%)
Scintigraphic abnormalitiesNDNDNDND 17/23 (74%)
Treatment???GC (2/6)
Hip surface replacement (1/6)
Tibial, fibular, and femoral osteotomy (1/6)