Diffuse Mesangial Sclerosis in a Child With Dyskeratosis Congenita Leading to End-stage Renal Disease.

Dyskeratosis congenita (DC) is a very rare inherited disorder. It is caused by dysfunction of telomere maintenance. It involves RNA telomerase components relevant to various mutations leading to a classic triad of physical findings consisting of nail dystrophy of the hands and feet, mucosal leukoplakia, and reticular pigmentation of the skin, most commonly on the head, neck, and trunk. Bone marrow failure along with pulmonary complications and malignancies are all common causes of premature death in patients with DC as well as other abnormalities. We report a new case of DC with impure nephrotic syndrome relevant to histopathologic signs of a diffuse mesangial sclerosis, leading to an early end-stage renal disease. Challenges remain to understand the diverse spectrum of DC especially in children. To the best of our knowledge this is the first case of DC associated to diffuse mesangial sclerosis.

Novel Mutation in the DKC1 Gene: Neonatal Hoyeraal-Hreidarsson Syndrome As a Rare Differential Diagnosis in Pontocerebellar Hypoplasia, Primary Microcephaly, and Progressive Bone Marrow Failure.

Primary microcephaly and severe developmental delay are complex but unspecific signs pointing to various genetic or acquired diseases. A concomitant finding of hematological failure may lead to the differential diagnosis of rare genetic diseases such as chromosome breakage disorders or diseases associated with telomere dysfunction. X-linked Hoyeraal-Hreidarsson syndrome (HHS) is a rare heterogenic disorder characterized by severe neurological impairment and progressive bone marrow failure. The latter represents the main cause of mortality, usually in early childhood. We report on the clinical course of an infant with HHS due to a novel mutation in the DKC1 gene and the particular finding of pontocerebellar hypoplasia.

Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up.

BACKGROUND: Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita-related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. PATIENT DESCRIPTION: We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. CONCLUSIONS: This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.