Table 1.
Clinical characteristics of patients with two BRCA1 mutations
| Features | A.II.1 | A.II.4 | B.II.2 | B.II.4 | Ref. 9 | Ref. 10 |
| BRCA1 genotype | p.W372X homozygote | p.W372X homozygote | p.L431X homozygote | p.L431X homozygote | p.846X/p.V1736A | p.233X/p.R1699W |
| Sex and karyotype | Female; 46;XX | Female; 46;XX | Male; 46;XY | Female; 46;XX | Female; 46;XX | Female; 46;XX |
| Age last follow-up | 5 y (deceased) | 6 y | 15.5 y | 7 y | 28 y (deceased) | 25 y (deceased) |
| Growth | ||||||
| At birth | SGA: 33 wks, 1.47 kg | AGA: 38 wks, 2.79 kg | SGA: term, 1.6 kg | AGA: 2.9 kg | nd | SGA: 1.99 kg |
| Postnatal | 5 y: 12 kg, 92 cm | FTT | Height < 3%ile | Height < 3%ile | Short stature | 25 y: 40 kg,135 cm |
| Intellectual disability | Developmental delay | Mild developmental delay | Yes (IQ: 50–69) | Yes (IQ: 62) | Developmental delay | Yes |
| Microcephaly | Yes (39 cm at 5 y) | Yes | Yes | Yes | Yes | Yes (microsomia) |
| Microphthalmia | Yes | Yes | Yes | Yes | nd | Yes (microsomia) |
| Skin pigment lesions | ||||||
| Hypopigmented | Yes | Yes | Yes | Yes | nd | Yes |
| Hyperpigmented | Yes | Yes | Generalized | No | nd | Yes |
| Café-au-lait spots | Yes | Yes | Yes | Yes | nd | No |
| Limb defects | Small edematous palms, soles | Small palms | Hypoplastic thumb (Blauth 2) | None | None | Proximally inserted thumbs, second digit captodactyly, second/third toe syndactyly |
| Dysmorphic features | Upslanting palpebral fissures, micrognathia | Triangular facies, upslanting eyes, epicanthus, cupped ears, short neck, micrognathia | None | None | Low anterior hairline, prominent nasal bridge, small alae nasi, macrognathia | Upslating palpebral fissures, sparse hair, hypertelorism, epicanthal folds, ptosis, strabismus, blepharophimosis, broad nasal bridge/nasal tip |
| Other | Optic nerve hypoplasia, bilateral hip dysplasia | Right first rib hypoplasia; Left 11 ribs | Right undescended testis, adrenal insufficiency | Heart defect (ASD and VSD), growth hormone deficiency | Duodenal stenosis, hyperextensible knees, history of hip dislocation, dental malocclusion | |
| Malignancy (age at dx) | T cell ALL (5y) | None | None | Neuroblastoma (2 y) | Ovarian cancer (28 y) | Breast cancer (25 y) |
| Chromosome breakage (case vs. control) | ||||||
| Spontaneous | 13.3% vs. 6.6% | nd | 6% vs. 0 | 2% vs. 0 | nd | 0.025 vs. 0.025 |
| Induced, DEB | 70% vs. 7% | 32% vs. 8% | 1.44 vs. 1.0 | 2.14 vs. 1.0 | nd | 2.2 vs. 0.05 |
| Induced, MMC | nd | 92% vs. 34% | nd | nd | nd | nd |
| Radials | Increased | Increased | nd | nd | nd | 30% vs. 0% |
| CBC/HbF | Normal | Normal | Normal | Normal | Normal | Normal |
| Bone marrow | t(1,16)+1q | nd | 15 y: cellular, no dysplasia | 2 y: cellular, adipocyte infiltration, no dysplasia; 7 y: normal | nd | nd |
| Brain MRI | nd | nd | Gliosis: periventricular and subcortical | Gliosis, prominent cortical sulci | nd | nd |
| Cancer family history | Intestinal and urological cancer, 2nd and 3rd degree relatives | Intestinal and urological cancer, 2nd and 3rd degree relatives | Uterine, esophageal, and lung cancer, 2nd and 3rd degree relatives | Uterine, esophageal, and lung cancer, 2nd and 3rd degree relatives | Breast, ovarian, intestinal cancer in 1st–4th degree relatives |
AGA, appropriate for gestational age; ASD, atrial septal defect; CBC, complete blood count; DEB, diepoxybutane; dx, diagnosis; FTT, failure to thrive; HbF, fetal hemoglobin; IQ, intelligence quotient; MMC, mitomycin C; MRI, magnetic resonance imaging; nd, not described; %ile, percentile; SGA, small for gestational age.