Spectral Domain Optical Coherence Tomography Findings in Myotonic Dystrophy
Myotonic dystrophy type 1 (DM1) is the most frequent adult-onset muscular dystrophy with an incidence of approximately 1:8000 among Caucasians. The disease, inherited as an autosomal dominant trait, is caused by an abnormal expansion of a CTG trinucleotide repeat located in the 3 ′ untranslated region of the DM1 protein kinase gene, on chromosome 19p35 [1,2]. DM1 is a multisystem disorder, which affects, beside the skeletal muscle, other organs and tissues, including the eye, with premature cataracts, low intraocular pressure (IOP) and retinal abnormalities [3,4].
Myotonic dystrophy type 1 (DM1) is an inherited multisystem disorder comprising progressive muscular dystrophy, myotonia, cardiac and endocrine abnormalities, and cataract. This disease follows an autosomal dominant trait and is caused by an expansion of a trinucleotide CTG-repeat in the 3 ’-untranslated region of the DMPK gene on chromosome 19 . Estimated prevalence of DM1 is 3-15/100,000 in the western world with an exceptional peak of 1:500 in Quebec (Canada) . Respiratory compromise may be caused by both respiratory muscle weakness  and blunting of the chemoreceptors wh ich regulate respiratory drive [3, 4].
AbstractMyotonic dystrophy is an autosomal dominant muscular dystrophy not only associated with muscle weakness, atrophy, and myotonia but also prominent multisystem involvement. There are 2 similar, but distinct, forms of myotonic dystrophy; type 1 is caused by a CTG repeat expansion in theDMPK gene, and type 2 is caused by a CCTG repeat expansion in theCNBP gene. Type 1 is associated with distal limb, neck flexor, and bulbar weakness and results in different phenotypic subtypes with variable onset from congenital to very late-onset as well as variable signs and symptoms. The classically described adult-onset form is the ...
Publication date: Available online 26 September 2018Source: Journal of American Association for Pediatric Ophthalmology and StrabismusAuthor(s): Tuy Nga Brignol, Patrice E. Fort, Dora Fix Ventura, Ramin Tadayoni, Alvaro Rendon
We report a 4-year-old male with congenital onset and progressive muscle weakness, feeding difficulties, joint contractures, respiratory insufficiency, ophthalmoparesis, cataracts and seizures.
ConclusionsIn patients undergoing GC therapy for DMD, the rate of cataract formation was slow and well tolerated, with a higher risk among deflazacort patients. The percentage of patients requiring cataract extraction or with elevated IOP was very small. These findings suggest that a schedule of annual eye examinations is appropriate.
AbstractDeflazacort (Emflaza ™) is a derivative of prednisolone with immunomodulatory and anti-inflammatory properties. Overall, in the treatment of boys with Duchenne muscular dystrophy (DMD), deflazacort is as effective as prednisone, but may be better tolerated. In a randomized, double-blind, phase 3 trial in boys with DMD , deflazacort and prednisone both preserved muscle strength more effectively than placebo after 12 weeks of treatment, with improvements being maintained until study end at week 52. Both active treatments were also associated with improved motor function. In the real-word setting, treatment...
Abstract Congenital cataract (CC) is clinically and genetically highly heterogeneous. Here, we enrolled a consanguineous kindred (LUCC15) from Pakistan, with three affected individuals suffering with CC. Exome sequencing revealed a transition mutation [c.149T>C; p.(Ile50Thr)] in INPP5K. Inositol polyphosphate-5-phosphatase K, encoded by INPP5K, is involved in dephosphorylation of phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4,5-trisphosphate. Recently, pathogenic variants in INPP5K have been reported in families with congenital muscular dystrophies, intellectual disability, and cataract. In our ...
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. Defects in INPP5A has been recently described as a cause of congenital muscular dystrophy, early-onset cataracts. Here we presented the clinical and pathological features of a patient with homozygous mutation in INPP5A gene.
Mutations in guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated alfa-dystroglycan. The firsts patients described with defects in this gene showed a broad phenotypic spectrum ranging from congenital muscle weakness, eye and brain structural abnormalities and intellectual delay to adult-onset limb-girdle muscular dystrophies without mental retardation. More recently, a relationship between defects in this gene has been associated to congenital myasthenic syndromes (CMS).
Glucocorticoid treatment, which has been shown to slow the decline of muscle strength and function in patients with Duchenne muscular dystrophy (DMD), can be associated with significant ocular side effects including cataract formation. However, the existing literature on this subjection is limited. To examine the prevalence and rate of development of cataracts in DMD patients on long term glucocorticoid treatment. This is a retrospective analysis of DMD patients who were evaluated in the Comprehensive Neuromuscular Center at Cincinnati Children's Hospital Medical Center (CCHMC) between 1/1/2010 through 12/31/2015.