The clinical features of the individuals in this study
| Feature . | P1 . | P2 . | P3 . | P4 . | P5 . | P6 . |
|---|---|---|---|---|---|---|
| Clinical findings | ||||||
| Age at last visit | Died at age 20 y | 10 y | 17 y | 11 y | 9 y | 5 y |
| Sex | Female | Male | Male | Male | Female | Male |
| Ethnicity | Turkish | Turkish | Turkish | French | Dutch | Dutch |
| Country | The Netherlands | The Netherlands | Turkey | France | The Netherlands | The Netherlands |
| Family | A | A | B | C | D | D |
| Variant in HEATR3 (ENST00000299192) | c.1751G>A p.(Gly584Glu) homozygous | c.1751G>A p.(Gly584Glu) homozygous | c.1337G>A p.(Cys446Tyr) homozygous | c.399 + 1G>T p.? heterozygous and c.719C> T p.(Pro240Leu) heterozygous | c.400T>C p.(Cys134Arg) homozygous | c.400T>C p.(Cys134Arg) homozygous |
| Systemic findings | ||||||
| Hematologic findings at presentation | Anemia | Anemia | Anemia | Anemia | Anemia | Anemia and thrombocytopenia |
| Body mass index (normal 18.5-24.9 kg/m2) | 29 kg/m2 | 23.7 kg/m2 | 28.1 kg/m2 | 18.7 kg/m2 | 22.8 kg/m2 | 16.3 kg/m2 |
| Height | < –3 SD | < –1 SD | < –4 SD | < –1 SD (growth hormone therapy at 4 y, < –3 SD at 2 mo) | < –1 SD | 0 SD |
| Head circumference | NA | Normal (0 SD) | < –3 SD | NA | > +1 SD | >+1 SD |
| Skeletal findings | Brachydactyly of hands, distal tapering of fingers, pes planus, hallux valgus | Pes planus, hallux valgus of the left foot, bilateral hypoplasia of the fourth and fifth toes | Severe genu valgum (operated), pes planus, brachydactyly of hands, hypoplasia of toes, sandal gap, cubitis valgus | None | Congenital hip dysplasia, preaxial polydactyly of right hand (operated), clinodactyly of left thumb, brachydactyly of first metacarpals, distal tapering of fingers | Brachydactyly of hands |
| Intellectual disability/ developmental delay | Mild | Mild | Mild | None | Mild | None |
| Facial dysmorphism | Synophrys, hypertelorism, low-set ears | Coarse hair, straight eyebrows, synophrys, protruding ears, full cheeks, narrow mouth | Down-slanted palpebral fissures, mild ptosis of left eye, widow's peak, micrognathy, protruding ears | None | Straight eyebrows | Down-slanted palpebral fissures, low-set ears |
| Skin findings | None | Cutis marmorata | Multiple nevi, facial freckling | Multiple nevi | None | None |
| Echocardiogram | NA | NA | Aortic regurgitation, dysplastic aortic valves | Interatrial septal defect (ostium secundum) | Normal | NA |
| Gastrointestinal findings | None | None | None | Persistent diarrhea, colitis | None | None |
| Other findings | Obesity, PCOS, hypotonia | Truncal obesity, ENT problems | Truncal obesity | None | Obesity | None |
| History of RBC transfusion | Yes | No | Yes | Yes | Yes | Transient |
| Response to corticosteroid | No | NA | Yes | No | NA | NA |
| Current treatment | — | None | Corticosteroid | Transfusion and iron chelation | Transfusion and iron chelation | None |
| Clinical course | Died of osteosarcoma at age 20 y | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition |
| Family history | ||||||
| Consanguinity | First-degree cousins | First-degree cousins | First-degree cousins | No | Likely | Likely |
| Family history | Yes, sibling (P1) | Yes, sibling (P2) | Yes, sibling | None | Yes, sibling (P6) | Yes, sibling (P5) |
| Feature . | P1 . | P2 . | P3 . | P4 . | P5 . | P6 . |
|---|---|---|---|---|---|---|
| Clinical findings | ||||||
| Age at last visit | Died at age 20 y | 10 y | 17 y | 11 y | 9 y | 5 y |
| Sex | Female | Male | Male | Male | Female | Male |
| Ethnicity | Turkish | Turkish | Turkish | French | Dutch | Dutch |
| Country | The Netherlands | The Netherlands | Turkey | France | The Netherlands | The Netherlands |
| Family | A | A | B | C | D | D |
| Variant in HEATR3 (ENST00000299192) | c.1751G>A p.(Gly584Glu) homozygous | c.1751G>A p.(Gly584Glu) homozygous | c.1337G>A p.(Cys446Tyr) homozygous | c.399 + 1G>T p.? heterozygous and c.719C> T p.(Pro240Leu) heterozygous | c.400T>C p.(Cys134Arg) homozygous | c.400T>C p.(Cys134Arg) homozygous |
| Systemic findings | ||||||
| Hematologic findings at presentation | Anemia | Anemia | Anemia | Anemia | Anemia | Anemia and thrombocytopenia |
| Body mass index (normal 18.5-24.9 kg/m2) | 29 kg/m2 | 23.7 kg/m2 | 28.1 kg/m2 | 18.7 kg/m2 | 22.8 kg/m2 | 16.3 kg/m2 |
| Height | < –3 SD | < –1 SD | < –4 SD | < –1 SD (growth hormone therapy at 4 y, < –3 SD at 2 mo) | < –1 SD | 0 SD |
| Head circumference | NA | Normal (0 SD) | < –3 SD | NA | > +1 SD | >+1 SD |
| Skeletal findings | Brachydactyly of hands, distal tapering of fingers, pes planus, hallux valgus | Pes planus, hallux valgus of the left foot, bilateral hypoplasia of the fourth and fifth toes | Severe genu valgum (operated), pes planus, brachydactyly of hands, hypoplasia of toes, sandal gap, cubitis valgus | None | Congenital hip dysplasia, preaxial polydactyly of right hand (operated), clinodactyly of left thumb, brachydactyly of first metacarpals, distal tapering of fingers | Brachydactyly of hands |
| Intellectual disability/ developmental delay | Mild | Mild | Mild | None | Mild | None |
| Facial dysmorphism | Synophrys, hypertelorism, low-set ears | Coarse hair, straight eyebrows, synophrys, protruding ears, full cheeks, narrow mouth | Down-slanted palpebral fissures, mild ptosis of left eye, widow's peak, micrognathy, protruding ears | None | Straight eyebrows | Down-slanted palpebral fissures, low-set ears |
| Skin findings | None | Cutis marmorata | Multiple nevi, facial freckling | Multiple nevi | None | None |
| Echocardiogram | NA | NA | Aortic regurgitation, dysplastic aortic valves | Interatrial septal defect (ostium secundum) | Normal | NA |
| Gastrointestinal findings | None | None | None | Persistent diarrhea, colitis | None | None |
| Other findings | Obesity, PCOS, hypotonia | Truncal obesity, ENT problems | Truncal obesity | None | Obesity | None |
| History of RBC transfusion | Yes | No | Yes | Yes | Yes | Transient |
| Response to corticosteroid | No | NA | Yes | No | NA | NA |
| Current treatment | — | None | Corticosteroid | Transfusion and iron chelation | Transfusion and iron chelation | None |
| Clinical course | Died of osteosarcoma at age 20 y | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition | Currently in good clinical condition |
| Family history | ||||||
| Consanguinity | First-degree cousins | First-degree cousins | First-degree cousins | No | Likely | Likely |
| Family history | Yes, sibling (P1) | Yes, sibling (P2) | Yes, sibling | None | Yes, sibling (P6) | Yes, sibling (P5) |
ENT, ears, nose, throat; NA, not available; PCOS, polycystic ovarian syndrome; RBC, red blood cell; SD, standard deviation.