Cone-rod dystrophy can be a manifestation of Danon disease

Background Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Methods Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Results Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fieldsdemonstrated central scotoma. The causal mutation was p. Gly384Arg in LAMP2; no mutations were found in RPGR. Conclusions This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease

Un diabète particulièrement compliqué

International audienc

Un diabète particulièrement compliqué

International audienceIntroductionLaminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes—characterized by a selective loss of adipose tissue—of which the partial Dunnigan family type is the most frequent.Case reportWe report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation.ConclusionFamilial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed.IntroductionLes laminopathies (maladies liées aux mutations des lamines A/C) sont des maladies génétiques rares, au spectre phénotypique étendu, incluant les syndromes lipodystrophiques (se caractérisant par une perte sélective de tissu adipeux), dont la forme familiale partielle de type Dunnigan est la plus fréquente.ObservationIl s’agit d’une patiente âgée de 55 ans, atteinte d’un diabète, rapportant de longue date des myalgies invalidantes. Son morphotype cushingoïde associé à une lipo-atrophie cutanée et à une hypertrophie musculaire, avec notion d’atteinte familiale, nous a conduit au diagnostic de lipodystrophie familiale partielle complexe avec mutation hétérozygote c.82C>T, p.Arg28Trp dans le gène LMNA.ConclusionLes syndromes lipodystrophiques partiels d’origine familiale peuvent revêtir des phénotypes variés, à dominance cardio-métabolique, pouvant mimer un diabète de type 2 particulièrement sévère. La prise en charge doit comporter la recherche attentive de troubles du rythme et/ou de la conduction paroxystique pourvoyeur de mort subite, ainsi qu’un conseil génétique. La leptine recombinante peut parfois être proposée