Central nervous system vasculopathy and Seckel syndrome: case illustration and systematic review

Abstract

Purpose To systematically review reported cases of Seckel syndrome (SS) and point out cases associated with central nervous system (CNS) vasculopathy and provide a summary of their clinical presentation, management, and outcomes including our illustrative case. Methods We conducted a search on the MEDLINE, PubMed, Google Scholar, and Cochrane databases using the keywords “Seckel + syndrome.” We identified 127 related articles reporting 252 cases of SS apart from our case. Moreover, we searched for SS cases with CNS vasculopathies from the same databases. We identified 7 related articles reporting 7 cases of CNS vasculopathies in SS patients. Results The overall rate of CNS vasculopathy in SS patients is 3.16% (n = 8/253), where moyamoya disease (MMD) accounted for 1.97%. The mean age is 13.5 years (6–19 years), with equal gender distribution (M:F, 1:1). The most common presenting symptoms were headache and seizure followed by weakness or coma. Aneurysms were mostly located in the basilar artery, middle cerebral artery, and internal carotid artery, respectively. Regardless of the management approach, 50% of the cases sustained mild-moderate neurological deficit, 37.5% have died, and 12.5% sustained no deficit. Conclusion A high index of suspicion should be maintained in (SS) patients, and MMD should be part of the differential diagnosis. Prevalence of CNS vasculopathy in SS is 3.16% with a much higher prevalence of MMD compared to the general population. Screening for cerebral vasculopathy in SS is justifiable especially in centers that have good resources. Further data are still needed to identify the most appropriate management plan in these cases.

Arterial stroke in a child with Seckel syndrome with a pattern of non‐moyamoya vasculopathy

“…Dilation of the CNS arteries described as aneurysms and MMD followed by their rupture, CNS hemorrhage, and strokes are among life‐threatening events observed in patients with primordial dwarfism type II; Majewski osteodysplastic primordial dwarfism type II 10 . In a systematic review, 253 cases of SS have been identified that eight cases developed CNS vasculopathy 5 . The overall rate of CNS vasculopathy in SS patients was reported to be 3.16% ( n = 8/253), where MMD accounted for 1.97% of the cases.…”

Central precocious puberty with hypothalamic hamartoma: the first case reports of 2 siblings with different phenotypes of Seckel syndrome 5

“…It is an autosomal recessive neurodevelopmental spectrum disorder characterized by a small head circumference, proportionate osteodysplastic primordial dwarfism, growth retardation, a wide spectrum of intellectual disability, and unique facial features including beak-like nose, sloping forehead, narrow face, large eyes and micrognathia. 3,4) Since it is a spectrum disorder, there have been many causative genetic variants for centrosomal proteins linked to microcephaly and dwarfism. 5) Variants in the CEP152 gene, located on chromosome 15q21.1, have been identified as the cause of Seckel syndrome 5 (SCKL 5).…”

“…9) The reported brain structural abnormalities related to SCKL include gyral hypoplasia, macrogyria, corpus callosum agenesis, cysts, hypoplastic cerebrum or cerebellum, pachygyria, brain herniations and central vasculopathy. 3,6) The pathogenesis of these abnormalities in SCKL is not fully understood. However, the centrosome plays a crucial role in cell division, and its activity appears to be critical to cerebral and neuronal development.…”

“…4) It is an autosomal recessive neurodevelopmental spectrum disorder characterized by intrauterine growth retardation that results in low birth weight and a small head circumference, proportionate osteodysplastic primordial dwarfism, growth retardation, variable intellectual disability, and unique facial features including beak-like nose, sloping forehead, narrow face, large eyes and micrognathia. 3,4) To date, there has been only one report on the effect of rhGH treatment on final height in children with SCKL. In that study, final height of two patients who…”

Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family

“…Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder with high clinical heterogeneity and is mainly characterized by a typical “bird-head” facial appearance, severe microcephaly, intellectual disability, and a proportionate short stature ( Seckel, 1960 ; Takikawa et al, 2008 ; Khojah et al, 2021 ). Other clinical symptoms, including low birth weight ( Majewski and Goecke, 1982 ), cardiovascular anomalies ( Khojah et al, 2021 ; Donmez et al, 2022 ), postnatal growth restriction ( O’driscoll et al, 2004 ), and myelodysplasia ( Verloes et al, 2013 ), were also occasionally reported.…”