Hypoparathyroidism-retardation-dysmorphism syndrome—Clinical insights from a large longitudinal cohort in a single medical center

Abstract

BackgroundHypoparathyroidism, retardation, and dysmorphism (HRD) Syndrome is a rare disease composed of hypoparathyroidism, retardation of both growth and development, and distinctive dysmorphic features. Here, we describe the long-term morbidity and mortality in a large cohort of HRD patients and suggest recommendations for follow up and treatment.MethodsMedical records of 63 HRD syndrome patients who were followed at Soroka Medical Center during 1989–2019 were reviewed retrospectively. Information regarding demographics, medical complications, laboratory findings, and imaging studies was collected.ResultsThe mortality rate was 52%. The main causes of death were infectious diseases including pneumonia, septic shock, and meningitis. Multiple comorbidities were found including brain anomalies in 90% of examined patients (basal ganglia calcifications, tightening of corpus callosum, Chiari malformation, hydrocephalous, and brain atrophy), seizures in 62%, nephrocalcinosis and/or nephrolithiasis in 47%, multiple eye anomalies were recorded in 40%, bowel obstructions in 9.5%, and variable expression of both conductive and senso-neural hearing loss was documented in 9.5%.ConclusionHRD is a severe multisystem disease. Active surveillance is indicated to prevent and treat complications associated with this rare syndrome.

Hypoparathyroidism-Retardation-Dysmorphism Syndrome due to a Variant in the Tubulin-Specific Chaperone E Gene as a Cause of Combined Immune Deficiency

“…Other important characteristics of the syndrome are significant delay in achieving developmental milestones, and significantly arrested gross and fine motor skill development. Speech is never achieved by some patients, whereas others have incomprehensible speech [ 4 ]. Eye and brain anomalies are common, as are multiple endocrine deficiencies (including hypothyroidism, adrenal insufficiency, and hypogonadism), epilepsy, and bowel obstruction.…”

“…Susceptibility to pneumococcal infections is a significant aspect of this syndrome, as many patients succumb in infancy due to these infections . In a recent publication reporting a long-term follow-up of a large cohort of HRD patients, 33 out of 63 patients died before reaching the age of 5 years [ 4 ]. All but one patient died from infections, which included septic shock, meningitis, and pneumonia.…”

“…All but one patient died from infections, which included septic shock, meningitis, and pneumonia. The introduction of amoxicillin prophylaxis as an institutional practice in 2000 has reduced the mortality rate under 5 years of age from 77 to 24% [ 4 ]. The first clinical descriptions of HRD patients by Richardson et al in 1990 reported normal immunoglobulin levels and a reduced number of T-lymphocyte subsets [ 1 ].…”