Origin / Italy / Portugal / Italy
Patient 1 / Patient 2 / Patient 3 / Patient 4 / Patient 5 / Patient 6
Sex / F / M / F / F / M / M
Neonatal period
Weight at birth
(weeks of gestation) / 2420 g (39) / 2640 g (39) / 2530 g (40) / 2820 g (40) / 3050 g (40) / 2900 (40)
OFC at birth / 31 cm (-3 SD) / 33 cm (-2 SD) / 31 cm (-3 SD) / 32 cm (-2 SD) / n.a. / n.a.
Last growth parameters (age) / 12 y / 9 y 3 mo / 12 y / 18 mo / 21 y / 15 y
Height (centile) / 122 cm (<3rd) / 109 cm (<3rd) / 124 cm (<3rd) / 71 cm (<3rd) / 157 cm (<3rd) / 151 cm (<3rd)
OFC (centile) / 51 cm (<3rd) / 48 cm (<3rd) / 48 cm (<3rd) / 42 cm (<3rd) / 47 cm (<3rd) / 48 cm (<3rd)
Cognitive development
Developmental delay / + / + / + / + / + / +
Intellectual disability / Mild / Mild / Mild-moderate / Mild / Severe / Severe
Speech / Dyslalia / Short sentences / Short sentences / Speech delay / Few words / Few words
Craniofacial anomalies
Wave shaped palpebral fissures / + / + / + / + / + / +
Malocclusion / + / + / + / + / + / +
Prominent upper incisors / + / + / + / + / + / +
Apparently low set ears / + / + / + / + / + / +
Skeletal and limb anomalies
Scoliosis / + / + / + / + / + / +
Short neck and trunk / + / + / + / + / + / +
Slender long bones / + / + / + / + / + / +
Tapering fingers / + / + / + / + / + / +
Single palmar crease / + / + / - / - / - / -
Delayed bone age / + / + / - / - / + / +
Other clinical features
Laryngeal anomalies / - / Laryngomalacia / Laryngeal stridor / Laryngeal stridor / - / -
Ocular anomalies / Strabismus / - / Bilateral cataract / - / - / LCA due to RDH12 mutation
Cardiac anomalies / Mitral valve prolapse
Flat T-waves (ECG) / Mild dilatation of the ascending aorta
Negative T-waves (ECG) / - / Ventricular septal defect / Systolic murmur / -
Thin hair and sparse eyebrows / + / + / + / + / + / +
miscellaneous / brachytelephalangy, bilateral clinodactyly of the 5th fingers, anomalies of the femoral heads / Cryptorchidism, epiphysiolysis of the femoral head, diffuse osteoporosis / Right preauricular tag / Hyperactive and aggressive behaviour
Pes planus
Genu valgum / Hyperactive and aggressive behaviour
Myopia, strabismus, astigmatism
Brain anomalies on MRI
Cerebellar hypoplasia / + / + / + / + / + / +
Enlarged cisterna magna / - / + / + / - / + / +
Other / Enlarged lateral ventricles / - / Thin corpus callosum
Enlarged lateral ventricles / Thin corpus callosum / Enlarged ventricles
Thin corpus callosum
Hypoplastic pons and mesencephalon / Enlarged ventricles
Thin corpus callosum
Hypoplastic pons and mesencephalon
Skull and orthopanoramic X-rays
Bialveolar protrusion / + / + / + / + / + / -
Prominent alveolar processes / + / + / + / + / + / -
Taurodontism / + / + / + / + / + / +
BRF1 mutations
BRF1 mutation maternal allele / c.677C>T
p.(Ser226Leu) / c.667C>T
p.(Arg223Trp) / c.677C>T
p.(Ser226Leu)
BRF1 mutation paternal allele / c.776C>T
p.(Thr259Met) / c.875C>A
p.(Pro292His) / c.677C>T
p.(Ser226Leu)
LCA, Leber congenital amaurosis
ECG, electrocardiogram
n.a., not available