Table 2.
Features of defined FND syndromes
| Distinguishing craniofacial features | Integumentary | Musculoskeletal | CNS/cognition | Genitourinary | References | |
|---|---|---|---|---|---|---|
| FND1 (ALX3) | long philtrum with periphiltral swelling, midline notch upper lip and alveolus, upper eyelid ptosis | midline dermoid cyst | – | normal cognition | – | Twigg et al., 2009 |
| FND2 (ALX4) | large skull defect, blepharophimosis, microphthalmia | total alopecia/sparse scalp hair | – | mildline intracranial lipoma, callosal anomaly, normal cognition to DD/ID | cryptorchidism, hypospadias | Kayserili et al., 2012; Kariminejad et al., 2014 |
| FND3 (ALX1) | extreme micropthalmia, upper eyelid colobomata, bilateral facial cleft, complete cleft plate | sparse eyelashes, absence of eyebrows | – | – | – | Uz et al., 2010 |
| Heterozygous SIX2 deletion (FND4?) | high anterior hairline, frontal bossing large anterior fontonelle, ptosis, epicanthus inversus, parietal foramina, cranio-synostosis (metopic, sagittal) | – | – | normal cognition | – | Hufnagel et al., 2016 |
| CFNS (EFNB1) | craniosynostosis (coronal), craniofacial asymmetry | longitudinal nail ridging, coarse thick hair | sloping shoulders with dysplastic clavicles (pseudoarthrosis), Sprengel deformity, chest deformity, duplicated/broad halluces, cutaneous syndactyly, congenital diaphragmatic hernia | callosal anomaly, normal cognition to mild DD/ID | – | van den Elzen et al., 2014 |
| AFND (ZSWIM6) | parietal foramina (variable) | – | preaxial polydactyly, unilateral or bilateral hemimelia, hypoplastic patellae | PVNH, callosal anomaly, absent olfactory bulbs, hypopituitarism, DD/ID | cryptorchidism | Smith et al., 2014 |
| OAFNS (unknown) | microtia, preauricular tags, facial asymmetry, mandibular hypoplasia, epibulbar dermoids (OAVS) | abnormal hairline and eyebrows | vertebral fusion, complex vertebral segmentation, rib anomalies | intracranial lipomas, encephalocoeles, callosal anomaly, calcification of the cerebral falx, DD/ID | – | Evans et al., 2013 |
| AFFND (unknown) | retinal coloboma, optic nerve atrophy, ulcerated corneae, polar cataracts, iris atrophy, micropthalmia, S-shaped palpebral fissure | abnormal hairline/eyelashes/eyebrow, hypoplastic nails | short stature, scoliosis, polysyndactyly of fingers, camptobrachydactyly, (hypoplastic distal phalanges, short metacarpals), hip dislocation, hypoplastic fibulae, tarsal anomalies, and tibio-talar subluxation | mixed hearing loss, epilepsy, DD/ID | hypospadias, bifid/shawl scrotum (mainly in AFFND2) | Prontera et al., 2011; Richieri-Costa et al., 1989 |
AFFND = Acrofrontofacionasal dysplasia; DD/ID = developmental delay/intellectual disability; IP = interpupillary distance; PVNH = periventricular nodular heterotopia; – = not present.