Hutchinson-Gilford progeria syndrome complicated with stroke: A report of 2 cases and literature review

Abstract

Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is a ultrarare, fatal autosomal dominant disorder. The pathogenesis of the disease is a mutation in LMNA, which leads to the accumulation of progerin in cells, impairing the normal physiological functions. Stroke and transient ischemic attack seriously affect the survival rate and quality of life of HGPS children, although the literature of this aspect is limited. This study summarizes the clinical manifestations and related imaging features of HGPS children with stroke to improve pediatric clinicians' understanding of this disease.

Case presentation: Both children have a de novo heterozygous mutation of LMNA [c.1824C > T ( p.G608G)]. Case 1. At the age of 4 years, the child had a cerebral infarction, which manifested as blurred vision and communication disturbance. Multiple abnormal signals were observed on the head MRI in the bilateral frontoparietal cortex, bilateral semiovale center, lateral ventricle, and deep frontal and parietal lobes. Multiple abnormal white matter signals on head MRA: bilateral internal carotid artery stenosis with basilar artery, and bilateral thickening of the posterior communicating artery. Case 2. At the age of 8.5 years, the child presented with cerebral infarction, which manifested as decreased muscle strength and choking after drinking water. MRI of the head showed that the bilateral frontal lobes were small with multiple abnormal signal shadows in the bilateral center of the semiovale and the lateral ventricle. Brain MRA revealed that the bilateral internal carotid arteries (C5-7) were narrow and uneven in thickness, and the A1 segment of the left anterior cerebral artery was narrower than the contralateral one. After symptomatic and supportive treatment, the two children improved.

Conclusion: Hemiplegia and physical weakness are the most prevalent stroke symptoms in children with HGPS, followed by headache, epilepsy, dysarthria, and psychosis as the primary manifestation in some children. Stroke in children with HGPS is mostly ischemic cerebral infarction caused by an insufficient cerebral blood supply. Pediatric cerebral infarction mainly occurs in the large vascular area, involving all vascular areas, with the internal carotid artery and middle cerebral artery being the most commonly accumulated.

Keywords: HGPS; LMNA; clinical manifestations; imaging features; stroke.

Figure 1

A 4-year-old boy patient. (A) The child has severe growth retardation; he showed distinctive facial features, scalp veins, generalized alopecia with sparse downy hairs, narrow nasal bridge, thin lips, and micrognathia. (B) Dry and stiff skin on the entire body, poor elasticity, and a lot of mottled pigmentation on the trunk. (C) Flexion deformity of the proximal phalangeal joints of both the fingers. (D) The shape of the head is enlarged, the anterior fontanelle and cranial suture are not closed, and the cranial plate of the parietal occipital region is thinned. (E) Multiple deformities of the ribs on both sides, dysplasia of the clavicle and scapula on both sides. (F) Cranial MRI at the time of onset: Multiple abnormal signals around the lateral ventricle. (G) Cranial MRA at the time of onset: The red arrow indicates bilateral internal carotid artery stenosis. (H) After the 3-month review, Cranial MRI: bilateral paraventricular lacunar infarction. (I) After the 3-month review, Cranial MRA: The red arrow indicates bilateral internal carotid artery stenosis similar to that noted earlier.

Figure 2

An 8.5-year-old boy patient. (A) The child showed distinctive facial features, with prominent forehead, baldness, exposed scalp veins, long and narrow nose, thin upper lip, and micrognathia. (B) The child exhibited flexion deformity of the distal knuckle joints of both the fingers, abduction of the bilateral wrist. (C) Anteroposterior pelvis X-ray showed bilateral hip dysplasia, bilateral femoral heads laterally positioned and left femoral head aseptic necrosis. (D) Long bones with thin diaphysis, widened metaphysis, and decreased bone density. (E) Cranial MRI at the time of onset: multiple abnormal signal shadows in the lateral ventricle. (F) Cranial MRA at the time of onset: bilateral internal carotid artery stenosis. The red arrow indicates internal carotid artery stenosis, and the yellow arrow indicates left anterior cerebral artery stenosis. (G) After the 3-month review, cranial MRI: multiple abnormal signal shadows in the lateral ventricle, and the left basal Nodal lesions. (H) After the 3-month review, cranial MRA: his left internal carotid artery, left middle cerebral artery and left cerebral artery had stenosis. The red arrow indicates internal carotid artery stenosis, the blue arrow indicates left middle cerebral artery stenosis, and the yellow arrow indicates left anterior cerebral artery stenosis.