Microcephaly-capillary malformation syndrome: the newly reported cases

Abstract

Microcephaly-capillary malformation syndrome (MICCAP: OMIM 614261) is a severe monogenic disorder inherited in an autosomal recessive manner caused by mutations in the STAMBP gene. There are less than 20 published cases of the syndrome to date. The paper reports three new cases of rare MICCAP syndrome. The cause of the disorder was confirmed in three affected individuals from two unrelated families by pedigree analysis, biochemical analysis, RFLP analysis and automated Sanger sequencing. The two brothers were homozygous for the potentially pathogenic STAMBP gene variant c.188A&gt;G (p.Tyr63Cys). Clinical phenotype of the girl from the second family resulted from the combination of two genetic disorders: galactosemia caused by the compound heterozygosity for the pathogenic GALT gene variants (c.563A&gt;G and c.855G&gt;T), and MICCAP caused by the STAMBP gene variants (c.204-5c&gt;g and с.668_669delCA), one of which originated de novo. The prevalence of microcephaly-capillary malformation syndrome in Russia is evaluated, it is one per 120,000 people (CI: 1/356 724–1/62 691). The carrier frequency is one per 173 people. The target STAMBP gene analysis makes the genetic confirmation of the MICCAP syndrome quicklier. When determining the tactics of diagnosis and therapy in each particular case, the possibility of combination of two rare genetic disorders in one patient should be considered.</jats:p