Multiple Endocrine Deficiencies are Common in Hypoparathyroidism–Retardation–Dysmorphism Syndrome

Abstract

Context The rare syndrome of hypoparathyroidism, retardation, and dysmorphism (OMIM #241410) is caused by the mutated tubulin chaperone E (TBCE) gene. This gene encodes a critical protein in the microtubule assembly pathway. Objective To evaluate the endocrine profile of HRD patients. Methods The study used a retrospective analysis of a large cohort of patients in a single university medical center. Sixty-three patients were diagnosed with HRD during 1990–2019; 58 of them had an endocrine evaluation. Main outcome measures: We investigated somatic growth parameters, the prevalence of hypoglycemia, growth hormone deficiency, hypothyroidism, hypogonadism, and cortisol deficiency. Results All patients were born small for gestational age, and severe growth retardation was found in all patients with mean height SDS of -8.8 (range -5.1 to -15.1) and weight SDS -18 (range -5.1 to -61.2). Serum IGF-1 concentrations were very low among the 21 studied patients: -2.32 SDS (range -0.6 to -2.7). Four out of 14 (28%) investigated patients had growth hormone deficiency. 55% of patients were hospitalized due to symptomatic hypoglycemia. adrenal glucocorticoid insufficiency was diagnosed in 22% of those tested. 36% of patients had hypothyroidism. Both hypogonadotrophic and hypergonadotrophic hypogonadism were observed. The main MRI findings were small anterior pituitary gland, small hippocampus, brain atrophy, thin corpus callosum, Chiari type I malformation, and septo-optic dysplasia. Conclusion Multiple endocrine abnormalities are common in patients with HRD syndrome. Periodic Screening of thyroid and adrenal functions is recommended.

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

“…Those include lissencephalies, cerebellar hypoplasia, and agenesis of the corpus callosum and cortical dysplasia as a part of migratory neuronal disorders. Indeed, structural abnormalities of the pituitary gland and corpus callosum have been reported in HRD (8,12,15,25). Similar developmental brain and eye anomalies were present in our cohort, emphasizing the role of TBCE during embryonal development of the central nervous system.…”

“…Other features of HRD include immunodeficiency with hyposplenism and impaired neutrophil function (6), ocular anomalies including microphthalmia, refractory errors, corneal opacities, and nystagmus (7), as well as impaired dentation with extensive carries and cryptorchidism. Recently, multiple other endocrinopathies have been recognized as being associated with HRD including hypothyroidism, cortisol deficiency, hypoglycemia, and hypogonadism (8). To date, the high mortality rate was attributed to infectious causes (6).…”

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

“…Eye and brain anomalies are common, as are multiple endocrine deficiencies (including hypothyroidism, adrenal insufficiency, and hypogonadism), epilepsy, and bowel obstruction. [ 5 ]. Susceptibility to pneumococcal infections is a significant aspect of this syndrome, as many patients succumb in infancy due to these infections .…”

Hypoparathyroidism Retardation and Dysmorphism syndrome due to mutation in Tubulin-specific chaperone E gene as a cause of combined immune deficiency

“…[6]. Autoimmunity was also reported as some patients were described with Hashimoto thyroiditis [4,7]. In this study we aimed to describe the immune phenotype of a relatively large cohort of HRD patients including cellular, humoral and neutrophil functions.…”

“…The common cause for HRD among the Arab Bedouin population is homozygosity for a founder mutation c.155_166delGCCACGAAGGG (p.Ser52_Gly55del) [3]. Other important features of the syndrome include brain anomalies, seizures, eye anomalies, hearing loss, multiple endocrine deficiencies, dimorphisms, and bowel obstruction [4]. Susceptibility to pneumococcal infections is a significant aspect of this syndrome, as many patients succumbed in infancy due to severe infections [6].…”