Table 1.
Review of clinical findings associated with three new BMP4 cases
| Subject | 1 | 2 | 3 |
|---|---|---|---|
| BMP4 variant | c.1052C>G p.S351*; c.751C>T p.H251Y | arr[hg19] 14q22.1q22.2(53001803_55443425)x1 | arr[hg19] 14q22.1q22.3(53854436_56266758)x1 |
| Other clinically relevant variants | arr[hg19] 17q21.3(43706876_44345048)x1 (Koolen de Vries syndrome) | ||
| Inheritance | c.1052C>G p.S351* de novo; c.751C>T p.H251Y inherited from mother; cis/trans status not determined | De novo | De novo |
| Sex | Male | Male | Female |
| Ethnicity | European/Vietnamese | Caucasian | White Mediterranean |
| Age at assessment | 4-years-old | 8-years-old | 13-years-old |
| Birth | 42-year-old G2P2 mother; delivery was at term through scheduled C-section; mild jaundice in the neonatal period | N/R | IUGR, born at 37 weeks, restricted growth from 32nd week, oligohydramnios |
| Birth weight in grams (%-tile) | 3345 g (36th, −0.35 SD) | 2520 g (5th, −1.66SD) | 2100 g (1st, −2.52SD) |
| Birth length in cm (%-tile) | N/R | 48 cm (23rd, −0.75SD) | 48 cm (30th, −0.54SD) |
| OFC at birth in cm (%-tile) | N/R | N/R | N/R |
| Weight in kg (%-tile) | At 3 years: 16.5 kg (90th, 1.21 SD) | At 3 years: 12.8 kg (15th, −1.0 SD) | At 5 years: 14.6 kg (5th, −1.67 SD); at 8.3 years: 20 kg (3rd, −1.90 SD); at 12.3 years: 32.7 kg (6th, −1.52 SD) |
| Height in cm (%-tile) | At 3 years: 97 cm (70th, 0.52 SD) | At 3 years: 90 cm (9th, −1.33 SD) | At 5 years: 104 cm (22nd, −0.78 SD); at 8.3 years: 119 cm (4th, −1.80 SD); at 12.3 years: 138.5 cm (2nd, −1.99 SD) |
| OFC in cm | At 3 years: 56.5 cm | At 3 years: 49 cm | At 5 years: 49 cm; at 8.3 years: 51 cm |
| Growth | Growth is normal, following upper percentiles for both height and weight; macrocephaly | Slow | Slow, poor weight gain but in the growth curve |
| Ophthalmological findings | Early myopia, not progressive | Bilateral Peters anomaly, sclerocornea | Exophthalmia, strabismus, slanting of palpebral fissures |
| Craniofacial dysmorphisms | Widely open fontanelles at birth, macrocephaly, prominence of the occiput, frontal bossing; slightly flat facial profile with wide-set and prominent eyes, flat infraorbital ridges, long eyelashes, and mild downslanting palpebral fissures; micrognathia and mild overbite with a high-arched palate; ears were over-folded and small | Large forehead, small nose | Craniosynostosis (metopic), surgery at 9 months; dolichocephaly |
| Brain MRI findings | Decreased volume of white matter in both cerebral hemispheres with the cortical margins nearly reaching the ventricular surface, suggestive of periventricular leukomalacia; unusual gyral patterns, particularly within the right occipital parietal region where there is a focal area of cortical thickness suggestive of polymicrogyria | Normal transfontannelar ultrasound | Nonspecific, generalized diminished white matter |
| Intellectual disability | Yes, mild | Yes, mild, requires special education services | Yes, mild to moderate |
| Global developmental delay | Yes, mild delay | Yes, mild | Yes, mild to moderate |
| Speech delay | Mild delay with his receptive and expressive language skills | No | Yes, mild to moderate |
| Hypotonia/motor delay | Mild delayed milestones, mild global hypotonia with wide based gait, clumsy, walking at 15 months | Yes, walked at 28 m | Hypotonia present |
| Hand and foot anomalies | Bilateral hypoplastic postaxial polydactyly involving hands (digits surgically removed), normal feet | Left hand postaxial polydactyly, left foot 4/5 syndactyly | Joint hyperlaxity |
| Additional clinical findings | Increased body hair on the back; two regressing hemangiomas in the lower back area; mild pectus excavatum; mild hypermobility in small hand joints, elbows, and knees; kidney ultrasound normal; oral aversion to solids as a child; hearing normal | Hyperextensible joints | Pelvic ectasia (unilateral), atrial septal defect, tiny aspect |
N/A not applicable, N/R not reported