Severe fascioscapulohumeral muscular dystrophy presenting with Coats’ disease and mental retardation
Introduction
Facioscapulohumeral muscular dystrophy (FSHMD) is an autosomal dominant muscle disease that affects approximately 5/100,000 individuals. The condition usually presents a typical pattern of periscapular and facial weakness, but shows wide variability with respect of age to onset and severity both between and within families [1]. FSHMD is associated with deletion of tandemly repeated DNA (D4Z4 repeats) from the subtelomeric region of chromosome 4q35 [2]. Identification of the chromosome 4 deletion permits DNA diagnosis in approximately 95% of cases and studies show that the size of the residual repeat fragment correlates approximately with disease severity and age of onset [3].
Retinal vascular changes and sensorineural hearing loss have been described in FSHMD [4]. The retinal changes include telangiectasia, microaneurysms and, in severe cases, an exudative retinopathy that mimics Coats’ disease [5], [6]. Hearing impairment appears particularly to be a feature of early onset disease [7] and its prevalence in adults is disputed [8]. In severe cases of FSHMD, with the smallest residual repeat fragments, symptoms may develop very early in childhood and these individuals are also the only ones reported to manifest mental retardation and epilepsy [9].
Section snippets
Case III-1
The index case was born in 1994. At the age of 10 months she was taken to her local doctor because her mother was concerned about her lack of movement. At 12 months, she was referred to an ophthalmologist having suddenly developed a squint. Examination showed that she could see well enough to pick up small objects when using her right eye, but would not allow occlusion of the right eye. Ophthalmoscopy of the right eye showed tortuous retinal vessels, extensive yellowish exudates at the
Methods
The enucleated eye was fixed in 10% buffered formalin and cut into parallel blocks according to standard laboratory procedure. Six micrometer-thick, paraffin-embedded sections were stained with hematoxylin–eosin, Perl’s Prussian blue and periodic acid-Schiff. For immunohistochemical study, paraffin-embedded sections were stained with primary antibodies against CD3 (dilution 1:400 DAKO), CD20 (dilution 1:200 DAKO), CD68 (KP1) (dilution 1:100, DAKO), and Mac-387 (dilution 1:50 DAKO).
DNA analysis
Microscopic examination
The retina was detached with large areas of infarction and was infiltrated by neutrophils and macrophages (Fig. 3A). Some of the inner retinal vessels contained fibrin thrombi at varying stages of organisation while others showed mural thickening. In areas, there was exudation of eosinophilic material into the retina. There were subretinal collections of exudate composed of fibrin with cholesterol clefts and foamy macrophages (Fig. 3B). Only a few strands of surviving retinal pigment epithelium
Discussion
This family demonstrates the variable clinical expression seen in FSHMD. Both girls were affected very early and with predominantly non-muscular features. Concern about poor physical activity in the index case was quickly overshadowed by progressive ocular and auditory disease and muscle involvement only became a major feature some four years later. The older child showed psychomotor retardation from birth and muscle disease was not recognised until she was 7–8 years old. The father of these
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Cited by (23)
Adult-onset Coats disease
2023, Survey of OphthalmologyHypotonia and Weakness: Level of the Muscle
2018, Volpe's Neurology of the NewbornEarly onset facioscapulohumeral dystrophy – a systematic review using individual patient data
2017, Neuromuscular DisordersCitation Excerpt :Inclusion criteria in some of the included studies, such as selection of patients with short repeat lengths or those with hearing difficulties, increases such bias. Moreover, utilizing the criteria for early onset/infantile FSHD by Brooke and Brouwer, which address motor symptoms, leads to the possible exclusion of patients with atypical (i.e. non-motor) onset of FSHD; we are aware of cases with a retinal vasculopathy presentation [47,71]. Due to the cross-sectional nature of the current review and the studies included herein, we remain unaware on the longitudinal course of early onset FSHD.
Facioscapulohumeral Dystrophy
2015, Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's ApproachRetinal telangiectasis detected during a vision screening examination in a child with hearing loss led to the diagnosis of facioscapulohumeral muscular dystrophy
2014, Journal of AAPOSCitation Excerpt :It is rare for children to present with ophthalmic findings leading to a diagnosis of FSHD. To our knowledge, only 3 cases in children under 2 years of age presenting with retinal telangiectasias and subsequently diagnosed with FSHD have appeared in the literature.4-6 Each of those patients had additional features related to infant-onset FSHD, most notably hearing loss.