A locus for sacral/anorectal malformations maps to 6q25.3 in a 0.3 Mb interval region.
Partial absence of the sacrum is a rare congenital defect that also occurs as an autosomal-dominant trait, whereas imperforate/ectopic anus is a relatively common malformation, usually observed in multiple congenital anomalies syndromes. We report on a girl born to healthy consanguineous parents (first cousins once removed) with anal imperforation and associated rectovaginal fistula and partial sacral agenesis. Facial dysmorphism included a high forehead, epicanthic folds, downslanting palpebral fissures, hypertelorism and a depressed nasal root. Brain MRI showed a bilateral opercular dysplasia with a unilateral (right) pachygyria; MRI and X-ray imaging of the spine disclosed a tethered cord associated with partial sacral agenesis. She showed a moderate developmental delay. Ophthalmologic examination evidenced bilateral microphthalmos and relative microcornea. Cytogenetic studies in our patient disclosed a pure de novo 6q25.3 --> qter deletion. By genotype analysis, we detected in our patient a maternal allele loss encompassing D6S363 and D6S446. Pure distal 6q deletion is a rare anomaly, reported in association with sacral/anorectal malformations (sacral agenesis, anal imperforation/ectopia) and never with cortical dysplasia. Pooling deletion mapping information in patients with pure terminal and interstitial 6q deletion allowed us to define a critical region spanning 0.3 Mb between the markers D6S959 and D6S437 for sacral/anal malformations. We hypothesize that haploinsufficiency for a gene within the deleted region may impair normal development of caudal structures, possibly acting on the notochordal development. European Journal of Human Genetics (2006) 14, 971-974. doi:10.1038/sj.ejhg.5201635; published online 17 May 2006.
Titomanlio
Luigi
L
Department of Child Neurology, AP-HP Robert Debré Hospital, Paris, France.
Giurgea
Irina
I
Baumann
Clarisse
C
Elmaleh
Monique
M
Sachs
Philippe
P
Chalard
François
F
Aboura
Azzedine
A
Verloes
Alain
A
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001006:Anus, Imperforate / Q000235:genetics*; D001921:Brain / Q000002:abnormalities / Q000000981:diagnostic imaging; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D003241:Consanguinity; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D018895:Microsatellite Repeats; D010375:Pedigree; D011859:Radiography; D012447:Sacrum / Q000002:abnormalities*