TABLE 1.
Clinical findings in individuals presenting RTS spectrum harboring variants in RECQL4 (data from our group, not published), ANAPC1, CRIPT and DNA2. Symptoms marked in green are observed in >50% of patients harboring mutations in any of the four genes, while findings marked in orange are gene-specific phenotypes seen in >50% of patients with mutations in only one of the four genes.
| RECQL4 | ANAPC1 | CRIPT | DNA2 | |
|---|---|---|---|---|
| No of individuals/families | 43/39 | 11/8 | 6/6 | 8/7 |
| Gender | 23F/20M | 5F/6M | 2F/4M | 3F/5M |
| Age range | 16 m—39 yo | NA | 70 days—11 yo | 2–18 yo |
| Anthropometric measurements | ||||
| Short stature (prenatal) | 34/43 | 7/11 (0/1) | 6/6 | 7/7 (6/7) |
| Z-score range | NR | NR | −2.89 to −5,3 | −5,64 to −8,77 |
| Microcephaly | NR | NR | 5/6 | 6/7 |
| Z-score range | −1.75 to—5.49 | |||
| Ophthalmologic findings | ||||
| Cataracts | 0/26 | 10/10 (juvenile) | 1/6 | 7/7 (6/7 congenital) |
| Retinal/optic nerve anomalies | 0/23 | - | 4/6 | 1/7 |
| Microphthalmia | 0/23 | 1/11 | NR | 4/7 |
| Corneal opacity | 0/23 | - | NR | 5/7 |
| Ectodermal findings | ||||
| Poikiloderma (generalized) | 41/43 | 11/11 | 4/4 | 7/7 (7) |
| Sparse hair/eyebrows and/or eyelashes | 29/43 | 10/11 | 5/5 | 7/7 |
| Dystrophic/small nails | 4/7 | 5/11 | 2/3 | 6/7 |
| Skeletal Findings | ||||
| Osteopenia/metaphyseal striations or irregular, wide metaphysis | 7/23 | 2/5 | 6/6 | 2/3 |
| Short metacarpals/phalanges | Short hands and/or feet (7/12) | 2/5 | 5/6 | 4/4 |
| Radial-ray defects | 14/40 | - | 1/6 (proximally placed thumb) | 0/7 |
| Axial abnormalities | 1/14 | NR | 6/6—scoliosis | 2/2 mild platyspondyly |
| 2/6 platyspondyly | ||||
| Endocrine anomalies | ||||
| Growth hormone deficiency (GH therapy) | NR | 5/10 (6) | - | 6/6 (5) |
| Hypothyroidism | NR | 2/10 | - | 5/6 |
| Genital anomalies | ||||
| Cryptorchidism | NR | 5/5 | 1/4 | 3/4M |
| Micropenis | 0/1 | 1/5 | - | 4/4M |
| Neurological findings | ||||
| Developmental delay/intellectual disability | 4/27 | 2/10 | 6/6 | 2/7 |
| Seizures | NR | NR | 4/6 | 0/7 |
| Other | ||||
| Recurrent pulmonary infections | NR | 3/10 (otitis media) | 6/6 (pulmonary) | 0/7 |
| Cancer (type) | 8/43 (6 osteosarcoma +2 skin cancer) | 0/10 | 0/6 | 0/7 |
| Death in childhood (cause) | 1/43 (NR) | 0/10 | 1/6 (pneumonia) | 0/7 |
| References | Cabral et al. (2008), Siitonen et al. (2009), Piard et al. (2015), Suter et al. (2016), Wang et al. (2018), Colombo et al. (2018), Zhang et al. (2021) | Ajeawung et al. (2019), Zirn et al. (2021) | Shaheen et al. (2014), Leduc et al. (2016), Akalin et al. (2023), Averdunk et al. (2023) | Di Lazzaro Filho et al. (2023) |