Case Report
Schimke immuno-osseous dysplasia, two new cases with peculiar EEG pattern

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Abstract

Introduction

Schimke Immuno-Osseous Dysplasia (SIOD) is an autosomal recessive multisystem disorder caused by pathogenic variants in the gene SMARCAL1. The clinical picture is characterized by spondyloepiphyseal dysplasia resulting in growth failure, nephropathy and T-cell deficiency. Neurologic manifestations include microcephaly, cognitive impairment, migraine-like headaches and cerebrovascular manifestations such as cerebral atherosclerotic vascular disease and reversible cerebral vasoconstriction. The role of SMARCAL1 deficiency in non-vascular neurological complications is still under debate. Epilepsy has been reported in a few patients, even in the absence of brain abnormalities. Data regarding electroencephalographic (EEG) patterns in SIOD are scarce

Methods

We describe the clinical, neuroradiological and EEG findings in two unrelated patients with SIOD showing a peculiar pseudo-periodic EEG pattern apparently not related to the cerebrovascular complications, since it was recognized both before and after cerebrovascular events

Conclusion

Our observations support the hypothesis that SMARCAL1plays an important role in neurodevelopment and brain function and expand the spectrum of neurological abnormalities related to SIOD.

Introduction

Schimke Immuno-Osseous Dysplasia (SIOD) is a rare (estimated prevalence of 1:1–3,000,000 live births) autosomal recessive disorder (OMIM:#242900), caused by pathogenic variants in SMARCAL1 gene, which encodes for a DNA-helicase involved in genomic integrity during DNA replication [1], [2], [3], [4]. The main clinical findings are spondyloepiphyseal dysplasia, growth failure, nephropathy (steroid-resistant glomerulonephritis leading to end-stage renal disease) and T-cell deficiency [5], [6]. Hyperpigmented macules, thin hair and dysmorphicfacial features (short neck, triangular face, broad nasal bridge, bulbous nasal tip) are common [7]. Neurological manifestations include migraine-like headaches, transient ischemic attacks or strokes. Cerebral ischemia can be associated with white matter alterations, moyamoya phenomena, alterations of cerebellar hemispheres and vermis [5], [8]. Mild intellectual disability (ID), microcephaly and seizures may be present in few cases, although most patients have normal cognitive development [5]. Cerebrovascular occlusive disease in SIOD may result from several predisposing factors, such as renal disease, systemic hypertension, immune dysfunction, dyslipidemia, early atherosclerosis, impaired vascular elastogenesis leading to disorganized internal elastic lamina and medial/intimal hyperplasia [9]. Recently, reversible cerebral vasoconstriction syndrome (RCVS), has been proposed as a novel mechanism for cerebrovascular complication in this rare condition [10]. Conversely, the role of SMARCAL1 deficiency in non-vascular neurological complications is still under debate. Some Authors stated that the developmental delay can be ascribed to the deleterious consequences of chronic illness and early, recurrent cerebral ischemic events [4], [5]. On the other hand, the presence of microcephaly, mild ID, seizures and EEG abnormalities in some patients also in absence of cerebrovascular damages suggest a relevant role of SMARCAL1 in brain development and function [5]. Data are scarce regarding the epileptic phenotype and EEG patterns in SIOD. Here we describe the clinical features and neuroimaging findings of two patients with SIOD showing focal seizures and a peculiar pseudo-periodic EEG pattern apparently not related to the cerebrovascular complications, thus expanding the spectrum of neurological features in SIOD.

Section snippets

Case report

This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the institution. Written consent was obtained from all family members of the enrolled children and considering patient’s medical history and phenotype, genetic counseling and test were performed.

Patient #1 is a 21-year-old female who received a clinical diagnosis of SIOD at 5 years of age, confirmed at 19 years of age by detection of a pathogenic homozygous variant of SMARCAL1

Discussion

Here we described a peculiar EEG pattern in two unrelated patients with SIOD, harboring different pathogenic variants in SMARCAL1, characterized by poorly structured background activity and pseudo-periodic rhythmic monomorphic sharpened delta waves (2.5–3 Hz) prevailing on fronto-temporal regions, resembling IRDA (intermittent rhythmic delta activity) [13]. In adults IRDA is frequently frontal and it is usually described in pathological conditions as toxic-metabolic encephalopathy,

Conflict of interest

None.

Acknowledgements

We would like to acknowledge Compagnia San Paolo/Italy (Research Grant ROL20573 and ROL9849 to GC) for the financial contribution. Thanks to Maria Giuseppina Baglietto who first recognized the peculiarity of the EEG pattern, we miss her.

The authors declare no competing interests.

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