EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype-phenotype correlation?
We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary syndrome (LMS). Features common to both families were an ectodermal dysplasia principally affecting tooth, breast and nipple development, dacryostenosis and severe micturition difficulties. Additional findings included post-axial digital hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and biopsy-proven interstitial cystitis. No individual had cleft lip. Split hand-split foot malformation (SHFM) occurred in one child-born after the molecular diagnosis was established. Unlike previous reports, the urinary symptoms were refractory to treatment with oral Fibrase and persisted into adulthood. Of the six cases/families now reported with EEC syndrome and Arg227Gln TP63 mutation, four have manifested this distinct urological abnormality, indicative of a genotype-phenotype correlation.
Maclean
Kenneth
K
Department of Clinical Genetics, Children's Hospital at Westmead (CHW), Sydney, Australia. k.maclean@victorchang.unsw.edu.au
Holme
Stephen A
SA
Gilmour
Elizabeth
E
Taylor
Mark
M
Scheffer
Heide
H
Graf
Nicole
N
Smith
Grahame H H
GH
Onikul
Ella
E
van Bokhoven
Hans
H
Moss
Celia
C
Adès
Lesley C
LC
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001120:Arginine / Q000235:genetics; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D013577:Syndrome; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014555:Urination Disorders / Q000235:genetics*
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D005973:Glutamine; D001120:Arginine