Table 1.
Clinical features of the patients in families A, B, and C
Family AFamily BFamily C
CaseA-II-1A-II-2B-II-3B-II-4C-II-1C-II-3
Ethnic origin Afghanistan Afghanistan Saudi Arabia Saudi Arabia Netherlands Netherlands 
Consanguinity Yes Yes Yes Yes No No 
IL6ST mutations (all homozygous) c.841C>T; p.Arg281* c.841C>T; p.Arg281* c.841C>T;p.Arg281* c.841C>T; p.Arg281* c.1699+4A>G c.1699+4A>G 
Gender Female Female Male Male Male Female 
Outcome Termination of pregnancy Death at day 2 Early neonatal death (2–3 h) Death in utero Death at day 2 Death at 6 yr 
Major clinical phenotype STWS STWS STWS STWS STWS STWS 
Clinical features 
Bone manifestations Limb bowing; severe deformities; growth defect Limb bowing; growth defect Bowed tubular bones Short tubular bones Bowing of legs; camptodactyly Bowing of femora; restricted limb extension; camptodactyly; joint instability; severe scoliosis; short stature 
Respiratory and dysautonomia symptoms NA Breathing difficulties; irreversible pulmonary hypertension; membranous disease in lungs; heart failure NA NA Respiratory distress Hyperthermia; hyporeflexia; motor delay; sucking and swallowing difficulties 
Immune and hematologic phenotype NA No eczema; no eosinophilia; thrombocytopenia NA NA NA Eczema at age 1 yra 
Other  Disseminated intravascular coagulation Multicystic dysplastic right kidney; dilated cisterna magna; small chest    
Weight NA Birth (GA36+3): 1,734 g; z-score: −2.29 NA NA Birth (GA 40+0): 2,700 g; z-score: −2.09 Birth (GA 40+0): 2,995 g; z-score −1.13 
2 8/12 yr: 8.9 kg; z-score: −2.33 
Height/length NA Birth (GA36+3): 36 cm; z-score: −4.77 NA NA Birth 47 cm (GA 40); z-score: −2.39 Birth (GA 40+0): 49 cm; z-score −1.23 
2 8/12 yr: 78 cm; z-score: −3.91 
Family AFamily BFamily C
CaseA-II-1A-II-2B-II-3B-II-4C-II-1C-II-3
Ethnic origin Afghanistan Afghanistan Saudi Arabia Saudi Arabia Netherlands Netherlands 
Consanguinity Yes Yes Yes Yes No No 
IL6ST mutations (all homozygous) c.841C>T; p.Arg281* c.841C>T; p.Arg281* c.841C>T;p.Arg281* c.841C>T; p.Arg281* c.1699+4A>G c.1699+4A>G 
Gender Female Female Male Male Male Female 
Outcome Termination of pregnancy Death at day 2 Early neonatal death (2–3 h) Death in utero Death at day 2 Death at 6 yr 
Major clinical phenotype STWS STWS STWS STWS STWS STWS 
Clinical features 
Bone manifestations Limb bowing; severe deformities; growth defect Limb bowing; growth defect Bowed tubular bones Short tubular bones Bowing of legs; camptodactyly Bowing of femora; restricted limb extension; camptodactyly; joint instability; severe scoliosis; short stature 
Respiratory and dysautonomia symptoms NA Breathing difficulties; irreversible pulmonary hypertension; membranous disease in lungs; heart failure NA NA Respiratory distress Hyperthermia; hyporeflexia; motor delay; sucking and swallowing difficulties 
Immune and hematologic phenotype NA No eczema; no eosinophilia; thrombocytopenia NA NA NA Eczema at age 1 yra 
Other  Disseminated intravascular coagulation Multicystic dysplastic right kidney; dilated cisterna magna; small chest    
Weight NA Birth (GA36+3): 1,734 g; z-score: −2.29 NA NA Birth (GA 40+0): 2,700 g; z-score: −2.09 Birth (GA 40+0): 2,995 g; z-score −1.13 
2 8/12 yr: 8.9 kg; z-score: −2.33 
Height/length NA Birth (GA36+3): 36 cm; z-score: −4.77 NA NA Birth 47 cm (GA 40); z-score: −2.39 Birth (GA 40+0): 49 cm; z-score −1.23 
2 8/12 yr: 78 cm; z-score: −3.91 

BW, birth weight; GA given in weeks + days; NA, not available. Z-scores of weight and length/height were calculated using Voigt et al. (2006) for fetuses and newborns and World Health Organization child growth standards (https://www.who.int/childgrowth/standards/en/) for C-II-3 in childhood.

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