Microphthalmia with linear skin defects (MLS) syndrome evaluated by prenatal karyotyping, FISH and array comparative genomic hybridization.
OBJECTIVE
To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome.


METHODS
We used karyotype analysis, FISH and array CGH to investigate an X;Y translocation. Replication studies were done on cultured amniocytes and lymphoblasts.


RESULTS
We describe a severe case of MLS syndrome that presented prenatally with multiple anomalies including cystic hygroma, microphthalmia, intrauterine growth restriction and a complex congenital heart defect. Cytogenetic analysis of amniocytes revealed an unbalanced de novo translocation between chromosomes X and Y [karyotype 46,X,der(X)t(X;Y)(p22.3;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2 (Tuple1 x 2)]. MLS diagnosis was made at birth and the prenatal karyotype was confirmed. Replication studies showed the derivative X chromosome was the inactive X. Array CGH confirmed the X and Y imbalances seen in the karyotype and also showed twelve BACs in the MLS region were deleted as a result of the translocation. FISH with BAC clones verified the array findings and placed the X breakpoint in Xp22.2, resulting in the amended karyotype, 46,X,der(X)t(X;Y)(p22.2;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2(Tuple1 x 2) arr cgh Xp22.33p22.2(LLNOYCO3M15D10 -->GS1-590J6)x 1,Yq11.222q23(RP11-20H21-->RP11-79J10)x 1.


CONCLUSIONS
The sensitivity of array CGH was valuable in detecting monosomy of the MLS critical region. Array CGH should be considered for the prenatal diagnosis of this syndrome.
Cain
Colyn Cargile
CC
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Saul
Daniel
D
Attanasio
Lisa
L
Oehler
Erin
E
Hamosh
Ada
A
Blakemore
Karin
K
Stetten
Gail
G
D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D000328:Adult; D041321:Chromosomes, Human, X; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006824:Hybridization, Genetic; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008850:Microphthalmos / Q000000981:diagnostic imaging / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012729:Sex Chromosome Aberrations; D012868:Skin Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics*; D013577:Syndrome; D016216:Ultrasonography, Prenatal