LAUSR

Dear Editor, Primary familial brain calcification (PFBC) is a rare neurological disease characterized by symmetrical bilateral calcifications, which are mostly located in the basal ganglia but can also be detected in other areas of the brain [1]. The estimated prevalence of PFBC is < 1/1.000.000 [2], with a male:female ratio of about 2:1 [3]. Although symmetrical brain calcifications are frequently observed in routine CT scans [4], the disease usually begins in the fourth or fifth decade of life with a variable association of psychiatric symptoms, cognitive decline, and extrapyramidal syndrome. These cardinal aspects can also be accompanied by a broad constellation of other clinical features and, depending on the prevalent location of the calcium deposits, they include headache [5], seizures, ataxia and dysarthria [3], and transient ischemic attack or stroke [6]. On the other hand, a significant proportion of patients are asymptomatic at the time of diagnosis [4]. To date, four genes (SLC20A2, XPR1, PDGFRB, and PDGFB) have been identified as being responsible for the disease, the mutations of which are transmitted with an autosomal dominant pattern. In this report, we describe clinical, neuroradiological and genetic aspects of a 49-year-old Ukrainian woman carrying a novel heterozygous nonsense mutation in the SLC20A2 gene. She was admitted to our Division for a full clinical and instrumental assessment because of radiological finding of cerebral calcifications in the basal ganglia, centrum semiovale, and cerebellar hemispheres, incidentally discovered after a head trauma. (Fig. 1A–F). The patient complained mood depression in the last 2 years and reported two episodes of complex visual hallucinations with predominantly threatening content. Her past medical history was remarkable for hypothyroidism in actual pharmacological hormonal balance. Extensive neuropsychological assessment revealed moderate depression along with subtle at tentional and visuoconstructional deficits, compatible with a non-amnestic, multiple domain mild cognitive impairment (MCI) (Fig. 1O). Laboratory tests found that the serum calcium, phosphorus, magnesium, calcitonin, and parathormone were all within the normal range, excluding any secondary form of brain calcification. EEG was not contributive. Brain MRI confirmed the presence of multiple calcifications symmetrically involving the cerebellar white matter and dentate nucleus, hippocampus, lentiform nucleus and pulvinar, caudate nucleus, and frontoparietal white matter also with perivascular distribution following the medullary vessels. These structures appeared of various signal intensities on T1-weighted images due to the surface area effect of the calcium crystals (Fig. 1G–L). The family history was contributive (Fig. 1M). The mother of the patient, who died at 70 years due to vascular complications of type II diabetes, suffered of memory disturbances and seizures since the age of 60 with radiological evidence of cerebral calcifications. Furthermore, an 80-year-old maternal aunt developed an unspecified tremorgenic syndrome and the maternal grandfather died at the age of 75 suffering from a psychiatric disorder. Performed after written informed consent, genetic analysis (Fig. 1N) showed the heterozygous variation c.1375G> in the SLC20A2 gene on the chromosome 8p11.21 (NM_006749), which resulted in a premature termination codon in position 459 (p.Glu459*). This mutation is not reported in the public accessible databases of human genetics (the Exome * Gianfranco Puoti [email protected]