Abstract
This study is a clinical report on twin females affected by primary microcephaly who
displayed at molecular analysis of heterozygous novel MCPH1 variant. The twins at the age of 10 years developed, in coincidental time, a diagnosis
of autoimmune juvenile thyroiditis. The main clinical features presented by the twins
consisted of primary microcephaly with occipitofrontal circumference measuring −2
or −3 standard deviation, facial dysmorphism, typical nonsyndromic microcephaly, and
mild intellectual disability. Molecular analysis of the major genes involved in primary
microcephaly was performed and the following result was found in the twins: MCPH1; chr8.6357416; c.2180 C > T (rs 199861426), p.Pro727. Leu; heterozygous; missense;
variant of uncertain significance (class 3). At the age of 10 years, the twins started
to have, in coincidental time, marked asthenia and episodes of emotiveness, and laboratory
exams disclosed a high level of antithyroid peroxidase leading to the diagnosis of
autoimmune juvenile thyroiditis with normal thyroid function. The novel heterozygous
MCPH1 variant found in the twins may be directly or indirectly involved in the onset of
the primary microcephaly. The thyroid disorder in the twins and its onset, in a coincidental
time, confirmed the effect of genetic predisposition on the pathogenesis of the immune
thyroiditis.
Keywords
MCPH1 variants - twins - primary microcephaly - autoimmune juvenile thyroiditis - Hashimoto's
thyroiditis
