Open AccessINPP5K-Related congenital muscular dystrophy: when juvenile cataracts give clues to a complex diagnosis
Author(s) -
Roberta Ismael Lacerda Machado,
Bruno de Mattos Lombardi Badia,
Wladimir Bocca Vieira de Rezende Pinto,
Igor Braga Farias,
José Laredo Filho,
Paulo Victor Sgobbi de Souza,
Acary Souza Bullé Oliveira
Publication year - 2021
Language(s) - English
Resource type - Conference proceedings
DOI - 10.5327/1516-3180.511
Subject(s) - hypotonia , medicine , cataracts , weakness , pediatrics , muscular dystrophy , congenital muscular dystrophy , muscle weakness , muscle biopsy , pathology , ophthalmology , anatomy , biopsy
Congenital muscular dystrophies (CMDs) are a group of rare genetic muscle diseases that present at birth or during infancy with hypotonia and weakness. Multiple forms of CMDs are also associated with cerebral and ocular phenotypes. Recently, INPP5K mutations have been described associated with CMD, cataracts and cognitive impairment. The INPP5K gene, encodes SKIP, one of the enzymes that phosphorylate the 5-phosphate position of phosphoinositides and is highly expressed in developing and adult brain, eye and muscle. Methods: We performed a case report of three Brazilian patients with INPP5KCMD with cataracts and intellectual disability under clinical follow-up at our service. Results: Case 1: 39 years old, female, presenting with progressive leg weakness since childhood, mild intellectual disability and bilateral cataracts at 20 years. Her 35-yearold sister (Case 2) had a similar clinical picture with limb-girdle weakness since childhood, cognitive impairment and early- onset bilateral cataracts. Both with myopathic pattern in EMG, elevated creatine phosphokinase (CK) and dystrophic pattern in muscle biopsy. Brain MRI studies disclosed a large megacistern in the elderly and no abnormalities in the younger sister. Genetic testing: c.653_655del(p.(Ser218del) in homozygosity in INPP5K gene. Case 3: 20 years old, female, normal motor development but learning difficulties since childhood. Presented with progressive pelvic girdle weakness in childhood and bilateral cataracts in late adolescence. Exams disclosed elevated CK, brain MRI was normal and genetic testing with the following mutation in INPP5K gene:c.[881_883del];[1088T>C];p.[Ser294del];[Ile363Thr]. Conclusion: We describe patients with CMD, cataracts and intellectual disability, caused by mutation in the INPP5K gene. In literature few cases are reported.