Autoimmune diseases, mental retardation, and dysmorphias. Cytogenetic and molecular investigations in siblings

Modern cytogenetic and moleculargenetic methods have become key technologies in patients with unexplained mental retardation during the last 15 years. Subtelomeric analysis with fluorescence in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) often detect unbalanced microdeletions (a parts per thousand currency signaEuro parts per thousand 5 Mb). These aberrations are mostly not detectable with conventional G-banded karyotypes. We report on results of telomeric investigations in siblings with an identical dysmorphic phenotype, mental retardation, and with coexisting autoimmune diseases (celiac disease, thyroiditis, hepatitis). Other family members were asymptomatic and without dysmorphias. In both patients, an identical inversion-duplication-deficiency on chromosome 18 (46,XX- and 46,XY, rec(18)dup(18)inv(18)(p11.32q22.3 similar to 23) was detected, maternally inherited through a balanced pericentric inversion (46,XX, inv(18)(p11.32q22.3 similar to 23)). Thus, the patients with the 18q-deletions were diagnosed with De Grouchy syndrome (OMIM 601808). Genetic counseling is necessary because of the recurrence risk. Based on the relatively small 18q23 deletions, this case report extends knowledge of the phenotypic spectrum in 18q deletion syndrome and clearly indicates the need for cytogenetic and molecular cytogenetic investigations in all dysmorphic patients with mental retardation and coexisting autoimmune disorders.