| |
Sex
|
M
|
M (proband)
|
M (son)
|
F
|
F
|
F
|
F
|
M
|
M
|
M
|
F (proband)
|
M (father)
|
M (brother)
|
M (brother)
|
| |
Age at last examination
|
10 yrs
|
32 yrs
|
8 months
|
13 yrs
|
9 yrs
|
4 yrs
|
5 yrs
|
23 yrs
|
8 yrs
|
Death: 40 yrs
|
26 yrs
|
Death: 56 yrs
|
Death: 30 yrs
|
31 yrs
|
| |
Consanguinity
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
|
General
|
Growth retardation/Hypotrophy (height; weight)
|
No
|
165 cm (−1.7 SD); 40 kg (BMI:14.7)
|
No
|
145 cm (−1.5 SD); 30 kg (BMI: 14.3)
|
120 cm (−1.9 SD); 15.8 kg (BMI:11)
|
102 cm (+0.2 SD); 14 kg (BMI:13.5)
|
91.3 cm (−3.9 SD); 12.3 kg (BMI:14.8)
|
No
|
No
|
163 cm (−2.1 SD); 53 kg (BMI:19.9)
|
No
|
No
|
No
|
No
|
| |
Delayed puberty
|
n/a
|
Yes (17 yrs)
|
n/a
|
Yes
|
n/a
|
n/a
|
n/a
|
No
|
n/a
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Normal IQ
|
Yes
|
Yes
|
n/a
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
Psychiatric disorders
|
No
|
No
|
n/a
|
No
|
No
|
No
|
No
|
No
|
No
|
Schizophrenia
|
No
|
No
|
No
|
No
|
|
Skin
|
Poikiloderma (early childhood)
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
- Face
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
- Exposed area/photosentivity
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
- Upper and/or lower limbs
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
Bullous lesions
|
Yes
|
No
|
No
|
No
|
No
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Eczema-like
|
Yes
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Ichthyosis-like
|
No
|
No
|
No
|
No
|
No
|
Yes
|
No
|
No
|
No
|
Yes
| | | | |
| |
Psoriasis-like
|
No
|
No
|
No
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Blaschko linear hypo/hyperpigmentation
|
No
|
No
|
No
|
No
|
No
|
Yes
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Lymphoedema of extremities
|
Yes
|
No
|
No
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
Yes
|
No
|
No
|
No
|
No
|
| |
Cellulitis
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Sclerosis of the digits
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
Yes
|
n/a
|
n/a
|
Yes
|
| |
Palmoplantar abnormalities
|
No
|
No
|
No
|
No
|
No
|
Palmar erythrosis and palmoplantar keratoderma
|
No
|
No
|
Palmar erythrosis
|
Palmoplantar keratoderma
| | | | |
| |
Hypohidrosis/Heat intolerance
|
Yes
|
Yes
|
Yes
|
n/a
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
n/a
|
Yes
|
Yes
|
Yes
|
Yes
|
|
Hair
|
Hypotrichosis/Alopecia
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
n/a
|
n/a
|
Yes
|
| |
- Scalp hair
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
- Eyebrows
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
| |
- Eyelashes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
No
|
No
|
No
|
|
Nails
|
Dysplasia
|
No
|
No
|
No
|
Yes
|
No
|
No
|
Yes
|
Yes
|
No
|
No
|
Yo
|
No
|
No
|
No
|
|
Muscle
|
Muscle weakness (Age at onset)
|
Yes (7 yrs)
|
Yes (11 yrs)
|
No
|
Yes (4y)
|
Yes (14 months)
|
No
|
Yes (infancy)
|
Yes (2 yrs)
|
Yes (8 yrs)
|
No
|
Yes (9 yrs)
|
n/a
|
n/a
|
n/a
|
| |
- Proximal lower limbs
|
Yes
|
yes
|
No
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
Yes
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
- Distal lower limbs
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
No
|
No
|
Yes
|
Yes
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
- Proximal upper limbs
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
- Distal upper limbs
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
- Neck: extensors/Sternocleidomastoid (SCM)
|
No
|
Yes (SCM), trunk extensors, abdominal muscles
|
No
|
n/a
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Amyotrophy
|
Yes
|
Yes
|
No
|
Yes
|
Yes
|
No
|
No
|
No
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Abolition of lower limb tendon reflex
|
No (weak reflexes)
|
Yes
|
No
|
Yes
|
Yes
|
No
|
n/a
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Tendon lengthening (age)
|
Yes (7 yrs)
|
Yes (11 yrs)
|
No
|
Yes (13 yrs)
|
No
|
No
|
No
|
No
|
No
|
No
|
Yes (14 yrs)
|
No
|
Yes (5 yrs)
|
No
|
|
Joints
|
Lower limbs contractures(Age at onset)
|
Triceps surae (6 yrs)
|
Triceps surae (7 yrs)
|
No
|
Triceps surae
|
Triceps surae (2 yrs) Hamstring (7 yrs)
|
Triceps surae (3 yrs)
|
Triceps surae (4 yrs)
|
No
|
Triceps surae (7 yrs)
|
No
|
Triceps surae
|
n/a
|
n/a
|
No
|
| |
Triceps surae muscle/Hamstring muscle
| | | | | | | | | | | | | | |
| |
Upper limb contractures
|
No
|
Biceps brachii (2–3 yrs) Carpal extensor
|
No
|
Yes
|
Yes
|
No
|
No
|
Yes (identified at age 23)
|
No
|
No
|
No
|
n/a
|
n/a
|
No
|
| |
Biceps brachii and carpal extensors
| | | | | | | | | | | | | | |
|
Spine
|
Scoliosis
|
No
|
Yes
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
|
Oral sphere
|
Dysphagia/Velopharyngeal insufficiency
|
No
|
Yes
|
No
|
n/a
|
Yes
|
No
|
No
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
|
Liver
|
Hepatomegaly
|
No
|
No
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
|
Pancreas
|
Steatorrhea/Exocrine insufficiency
|
Yes
|
n/a
|
n/a
|
n/a
|
No
|
Yes
|
Yes
|
Yes
|
No
|
No
|
n/a
|
n/a
|
n/a
|
n/a
|
|
Eye
|
Cataract
|
No
|
No
|
No
|
Yes
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
Other
|
No
|
No
|
No
|
No
|
No
|
No
|
No
|
Shallow orbits with mild restriction of medial rectus action OU; right macular pigmentary changes
|
No
|
Corneal thickness
|
No
|
No
|
No
|
No
|
|
Blood test
|
SCK (UI/l) (maximum)
|
N
|
460
|
n/a
|
500
|
340
|
370
|
N
|
372
|
n/a
|
N
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Blood count abnormalities (maximum)
|
Eosinophilia 1.5 × 10e9/L
|
N
|
n/a
|
N
|
Eosinophilia 0.8 × 10e9/L
|
N
|
Eosinophilia 0.9 x 10e9/L
|
PLT count: 78 x 10e9/L, MCV: 98.4 fL
|
N
|
N
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
Liver function
|
n/a
|
N
|
n/a
|
Cholestasis
|
n/a
|
SGOT: 63 IU/L (<53); SPGT: 56 IU/L (<36); ALP: 308 IU/L (<335); GGT: 53 IU/L (<26)
|
SGOT:210 IU/L (<40); SGPT: 151 IU/L (<35); ALP: 772 IU/L (<315); Bili: 33 mmol/l (<14)
|
SGOT: 100 IU/L (<38); SGPT: 132 IU/L (<41); ALP:129 IU/L (<129); GGT:106 IU/L (<58)
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
|
Muscle exploration
|
EMG: myogenic
|
Yes
|
n/a
|
n/a
|
Yes
|
Yes
|
n/a
|
n/a
|
N
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
| |
MRI/CT-scan
|
Adiposis (MRI)
|
Adiposis (MRI)
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
Atrophy of paraspinal and rectus abdominis muscles (CT scan)
|
n/a
|
Adiposis (MRI)
|
n/a
|
n/a
|
n/a
|
n/a
|
|
Lung exploration
|
PFT (pulmonary Function Test): Restrictive syndrome
|
Yes (asthma)
|
Yes
|
n/a
|
n/a
|
Yes
|
n/a
|
Yes
|
Yes
|
Yes (poor participation)
|
Yes
|
Yes
|
Yes
|
Yes
|
No
|
| |
- FVC (% of predicted)
|
1.61 L (83 %)
|
1.82 L (42 %)
|
n/a
|
n/a
|
38 %
|
n/a
|
53 %
|
64 %
|
1.33 L (86 %)
|
1.47 L (36 %)
|
78 %
|
n/a
|
34 %
|
91 %
|
| |
- FEV1 (% predicted)
|
1.25 L/min (73 %)
|
2.02 (44 %)
|
n/a
|
n/a
|
n/a
|
n/a
|
56 %
|
n/a
|
1.32 L/min (101 %)
|
1.15 L/min (34 %)
|
n/a
|
n/a
|
37 %
|
n/a
|
| |
- FEV1/FCV (%)
|
78 %
|
111 %
|
n/a
|
n/a
|
n/a
|
n/a
|
N
|
n/a
|
99 %
|
78 %
|
86 %
|
n/a
|
90 %
|
76 %
|
| |
- DLCO
|
n/a
|
41 %
|
n/a
|
n/a
|
51 %
|
n/a
|
n/a
|
n/a
|
0.87 (64 %)
|
Not feasible
|
67 %
|
n/a
|
34 %
|
88 %
|
| |
PET/CT-scan
|
n/a
|
No pulmonary fibrosis (CT scans)
|
n/a
|
n/a
|
No fibrosis
|
n/a
|
No fibrosis
|
No pulmonary fibrosis; presence of a nodule
|
n/a
|
Pulmonary fibrosis, slightly hypermetabolic lesions
|
n/a
|
n/a
|
n/a
|
n/a
|
|
Pathology
|
Peripheral muscle
|
Adiposis
|
Dystrophy, fibrosis, adiposis
|
n/a
|
Dystrophy, fibrosis, adiposis
|
Fibrosis, adiposis
|
n/a
|
n/a
|
Fibroadipose replacement, endomysial fibrosis, atrophic and hypertrophic fibers, central nuclei
|
n/a
|
n/a
|
n/a
|
n/a
|
Fatty infiltration
|
n/a
|
| |
Skin
|
Sclerodermiform aspect, Elastin anomalies
|
n/a
|
n/a
|
n/a
|
RTS-like
|
n/a
|
Hyperkeratosis, parakeratosis, hypergranulosis, acanthosis, spongiosis. Numerous apoptotic keratinocytes.
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
Sclerodermiform aspect, fibrosis, elastic tissue degeneration
|
n/a
|
| |
Visceral organs
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
Pulmonary fibrosis
|
Pulmonary, esophageal and mediastinal lymph node fibrosis, pancreas fatty infiltration
|
n/a
|
| |
Vasculature
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
n/a
|
Elastic degeneration, medial calcification
|
n/a
|
|
Gene analysis
|
RECQL4
|
No mutation
|
No mutation
|
n/a
|
No mutation
|
No mutation
|
No mutation
|
No mutation
|
No mutation
|
No mutation
|
No mutation
|
n/a
|
No mutation
|
No mutation
|
n/a
|
| |
Other genes
|
No
|
CAPN3, LMNA, CAV3 (no mutation)
|
No
|
No
|
SMN1 (no mutation)
|
No
|
No
|
CLCN1- c.2509-3C > T (intronic between exons 22 and 23); c.2926 C > T (p.976 R > X, nonsense mutation)
|
No
|
No
|
No
|
No
|
No
|
No
|
| |
FAM111B
|
c.1879A > G (p.Arg627Gly)
|
c.1879A > G (p.Arg627Gly)
|
c.1879A > G (p.Arg627Gly)
|
c.1879A > G (p.Arg627Gly)
|
c.1883G > A (p.Ser628Asn)
|
c.1883G > A (p.Ser628Asn)
|
c.1883G > A (p.Ser628Asn)
|
c.1883G > A (p.Ser628Asn)
|
c.1874C > A (p.Thr625Asn)
|
c.1289A > C (p.Gln430Pro)
|
c.1861 T > G (p.Tyr621Asp)
|
n/a
|
c.1861 T > G (p.Tyr621Asp)
|
c.1861 T > G (p.Tyr621Asp)
|
| |
Inheritance
|
De novo
|
De novo
|
Paternal inheritance
|
n/a
|
No maternal inheritance
|
De novo
|
De novo
|
De novo
|
de novo
|
n/a
|
Paternal inheritance
|
n/a
|
Paternal inheritance
|
Paternal inheritance
|
