Table 1.
ERF mutations and the associated phenotype
| Patient (kindred) | Gender (age at last assessment—years) | Mutation and parental origin | Relationship to proband | Synostosis | Facial dysmorphism | Other phenotypic features | Chiari‐1 malformation |
|---|---|---|---|---|---|---|---|
| 1 (K1) | F (19) | c.891_892delAG; p.(G299Rfs*9) de novo | Proband | Bicoronal unilambdoid | OHT, exorbitism, malar hypoplasia, | Factor XI deficiency, celiac disease | Yes (early) |
| 2 (K2) | M (11) | c.301C>T; p.(R101W) maternal (inferred) | Proband | Pansynostosis | OHT, exorbitism, malar hypoplasia | Asthma. Lactose intolerance. | Yes (early) |
| 3 (K2) | M (12) | c.301C>T; p.(R101W) maternal (inferred) | Brother | None | OHT | Unilateral polymicrogyria | No |
| 4 (K2) | F (9) | c.301C>T; p.(R101W) maternal (inferred) | Maternal half‐sibling | None | None | None | No |
| 5 (K3) | F (7) | c.247C>T; p.(R83W) maternal | Proband | Pansynostosis | OHT, exorbitism, malar hypoplasia | Short, broad DP of thumbs, allergy to gelofusine | Yes (early) |
| 6 (K3) | M (6) | c.247C>T; p.(R83W) maternal | Brother | Sagittal bilambdoid | OHT, exorbitism, malar hypoplasia | Broad DP of thumbs, halluces | No |
| 7 (K3) | F (adult) | c.247C>T; p.(R83W) maternal | Mother | Suspected sagittal | OHT, mild exorbitism | None | N/K |
| 8 (K3) | M (5) | c.247C>T; p.(R83W) maternal | Maternal cousin | Sagittal, bilambdoid, unicoronal (squamosal) | None | None | No |
| 9 (K3) | F (adult) | c.247C>T; p.(R83W) maternal | Maternal aunt | None | None | None | N/K |
| 10 (K3) | F (adult) | c.247C>T; p.(R83W) unknown | Maternal grandmother | None | None | Ovarian carcinoma | N/K |
| 11 (K3) | F (adult) | c.247C>T; p.(R83W) maternal | Maternal aunt | None | None | None | N/K |
| 12 (K3) | M (adult) | c.247C>T; p.(R83W) maternal | Maternal uncle | None | None | ONHD | N/K |
| 13 (K3) | F (6) | c.247C>T; p.(R83W) maternal | Maternal cousin | Unilambdoid unicoronal (squamosal) | OHT, mild exorbitism | None | No |
| 14 (K3) | M (4) | c.247C>T; p.(R83W) maternal | Maternal cousin | Pansynostosis | OHT, mild exorbitism | None | No |
| 15 (K4) | M (10) | c.1390_1391dupCC; p.(K465Lfs*67) paternal | Proband | Pansynostosis | OHT, exorbitism, malar hypoplasia | Left proximal radio‐ulnar synostosis, C5/6 vertebral fusion, broad thumbs | No |
| 16 (K4) | M (adult) | c.1390_1391dupCC; p.(K465Lfs*67) unknown | Father | Suspected sagittal | OHT, exorbitism, | None | N/K |
| 17 (K5) | F (7) | c.248G>A; p.(R83Q) paternal | Proband | Pansynostosis | OHT, exorbitism, malar hypoplasia, medial epicanthic folds | Bilateral 4th toe clinodactyly | Yes (early) |
| 18 (K5) | M (adult) | c.248G>A; p.(R83Q) unknown | Father | Sagittal bicoronal | OHT, exorbitism, malar hypoplasia, medial epicanthic folds | Broad thumbs | Yes |
| 19 (K6) | M (7) | c.1201_1202del; p.(K401Efs*10) unknown | Proband | Pansynostosis | OHT, malar hypoplasia, frontal bossing, long philtrum, high arched palate, low‐set ears | Inverted nipples. Bilateral 5th finger clinodactyly, broad DP of halluces, sacral dimple | Yes |
| 20 (K7) | M (19 mo) | c.202G>C; p.(G68R) paternal | Proband | Sagittal unilambdoid | Hydrocephalus, macrocephaly, dysplastic auricles | None | No |
| 21 (K7) | M (19 mo) | c.202G>C; p.(G68R) paternal | Dizygotic twin | Metopic | Dysplastic auricles | None | No |
| 22 (K7) | M (adult) | c.202G>C; p.(G68R) unknown | Father | Suspected sagittal | None | None | N/K |
| 23 (K8) | M (1) | c.161A>G; p.(E54G) maternal | Proband | Unilambdoid | Medial epicanthic folds, short up‐turned nose | None | No but small posterior fossa |
| 24 (K8) | F (adult) | c.161A>G; p.(E54G) unknown | Mother of proband | Suspected sagittal | OHT, exorbitism | None | N/K |
| 25 (K9) | F (3) | c.1201_1202delAA; p.(K401Efs*10) paternal | Proband | Unicoronal | Long philtrum, short up‐turned nose, | Joint hypermobility | No |
| 26 (K9) | M (adult) | c.1201_1202delAA; p.(K401Efs*10) unknown | Father | None | OHT, mild malar hypoplasia and prognathism | None | N/K |
| 27 (K10) | F (5) | c.547C>T; p.(R183*) unknown | Proband | Sagittal | OHT, mild exorbitism, malar hypoplasia | None | No |
| 28 (K11) | F (15) | c.547C>T; p.(R183*) paternal | Proband | Sagittal bilambdoid | OHT, mild exorbitism, malar hypoplasia | Short lateral metatarsals | No |
| 29 (K11) | M (17) | c.547C>T; p.(R183*) paternal | Brother | Sagittal bilambdoid | OHT, mild exorbitism, malar hypoplasia, low‐set ears | Short lateral metatarsals | No |
| 30 (K11) | M (adult) | c.547C>T; p.(R183*) unknown | Father | None | OHT, mild exorbitism, malar hypoplasia | None | N/K |
| 31 (K12) | M (4) | c.157G>A; p.(G53R) unknown | Proband | Sagittal | OHT, exorbitism, malar hypoplasia, low‐set ears, open mouth appearance | None | No |
| 32 (K13) | M (4) | c.652C>T; p.(R218*) maternal | Proband | Sagittal, bilambdoid (sphenoidal) | OHT, mild exorbitism | Oculocutaneous albinism familial short stature | No |
| 33 (K13) | F (adult) | c.652C>T; p.(R218*) unknown | Mother | None | OHT, mild exorbitism | None | N/K |
| 34 (K14) | M (9) | c.247C>T; p.(R83W) maternal | Proband | Sagittal bilambdoid | OHT, exorbitism | None | No |
| 35 (K15) | F (15 mo) | c.1270C>T; p.(Q424*) suspected de novo | Proband | Sagittal bilambdoid | OHT | None | No |
| 36 (K16) | M (14) | c.1A>T p.? suspected de novo | Proband | Pansynostosis | OHT, mild exorbitism, malar hypoplasia | Broad thumbs/first toes | Yes (early) |
Abbreviations: DP = distal phalanx; F = female; K = kindred; M = male; mo = months; N/K = not known; OHT = orbital hypertelorism; P = patient. Note. Unconfirmed clinical diagnoses are in italics. Where the parental origin has been stated it has been confirmed by direct mutation testing. Where parental samples were not available the origin has been recorded as “unknown”. For the parents of a proband who carried the same ERF mutation, the origin in them was generally “unknown” as the grand‐parental samples were not available. In K2 the parental origin could be inferred. In two patients the mutation was suspected to be de novo on clinical grounds but parental samples were not available.
Mutation nomenclature is based on NM 006494 (cDNA) and NP 006485 (protein).
The bold text represents the Probands.