Microcephaly-capillary malformation syndrome

Shchagina OA, Semenova NA, Bessonova LA, Larshina EA, Beskorovainiy NS, Zakharova EYu, Ryzhkova OP, Poliakov AV
About authors

Bochkov Research Center for Medical Genetics, Moscow, Russia

Correspondence should be addressed: Olga A. Shchagina
Moskvorechye, 1, Moscow, 115522; ur.baland@anigahcs, ur.liam@o_anigahcs

About paper

Compliance with ethical standards: the study was approved by the Ethics Committee of the Research Centre for Medical Genetics (protocol № 5/8 dated November 12, 2018). The informed consent to molecular genetic testing, and anonymity-preserving clinical and molecular genetics data publishing (including photos and videos) was submitted by all participants or their legal representatives.

Author contribution: Shchagina OA — study design, molecular genetic analysis, frequency estimation, statistical analysis; Semenova NA, Bessonova LA — clinical examination and genetic counseling of the patients’ families; Larshina EA — biochemical assays, GALT gene analysis; Beskorovainiy NS — exome sequencing data processing; Zakharova EYu — biochemical analysis, prevalence calculation; Ryzhkova OP — pathogenicity analysis of genetic variants, exome sequencing; Poliakov AV — selection of primers for molecular genetic analysis.

Received: 2020-05-18 Accepted: 2020-06-03 Published online: 2020-06-19

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>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>G and c.855G>T), and MICCAP caused by the STAMBP gene variants (c.204-5C>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.

Keywords: galactosemia, GALT, microcephaly, hemangioma, capillary malformation, STAMBP