ABSTRACT
Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case shows the importance of fetal exome where the parents were carriers for 2 ciliopathy genes (TMEM138 & SDCCAG8). Diagnosis in this case was confirmed by fetal exome sequencing (Joubert syndrome). Multiexon deletion in TMEM67 and KIF14 present in trans was identified in the third case (Meckel syndrome), likely resulting in digenic inheritance. Conclusion: We report 2 cases of Meckel syndrome with a novel variant and multiexon deletion, and 1 case of Joubert syndrome which depicts the limitations of preconceptional carrier screening in ciliopathies due to overlapping phenotypes.
Subject(s)
Abnormalities, Multiple , Ciliary Motility Disorders , Ciliopathies , Eye Abnormalities , Polycystic Kidney Diseases , Humans , Encephalocele/diagnosis , Encephalocele/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Eye Abnormalities/diagnosis , Eye Abnormalities/genetics , Cerebellum/pathology , Retina/pathology , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/pathology , Polycystic Kidney Diseases/diagnosis , Polycystic Kidney Diseases/genetics , Polycystic Kidney Diseases/pathology , Ciliopathies/diagnosis , Ciliopathies/genetics , Ciliopathies/pathology , Mutation , Antigens, Neoplasm , Cytoskeletal Proteins/genetics , Cell Cycle Proteins/geneticsABSTRACT
OBJECTIVES: To study clinical response to treatment with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) in a cohort of Gaucher disease. METHODS: Retrospective data of 8 patients of Gaucher disease was compiled. The treatment included all three currently available enzyme replacement therapies as well as substrate reduction therapy with Eliglustat. The relevant blood investigations were done in follow-up visits. The assessment of the effects of long-term treatment over varying periods up to 13 y was done with various issues related to the course of therapy documented. RESULTS: Improvement in hematological parameters was seen in all patients. Reduction of spleen size occurred in 7 of 8 patients (87.5%). One patient had 2 successful pregnancies while on therapy. A distinct patient with type 3 Gaucher disease developed complication in the form of Gaucheroma within the spleen. CONCLUSIONS: Awareness about the disease and the efficacy of the therapies amongst pediatricians will help in early diagnosis and better outcomes. The available therapies have changed the outcome of the patients and improved the quality of life in patients with Gaucher disease. The data of Indian patients is important at this juncture when under Rare Disease Policy, government funding has become available for ERT for Gaucher disease patients in India.