A young boy with ventricular arrhythmias and thyroid dysgenesis: two genes are not enough?

Abstract Congenital hypothyroidism (CH) may be caused by biallelic variants in the TSHR gene. CH due to thyroid dysgenesis has also been linked to pathogenic variants of the nucleotide kinase 2, homeobox 5 (NKX2-5) gene, which can also cause sudden cardiac death from ventricular arrhythmia. In particular, the NKX2-5 p.Arg25Cys missense variant has been repeatedly reported in patients with congenital heart defects and, more rarely, with hypogonadism. We report the case of a 7 year old boy with ventricular arrhythmias, thyroid dysgenesis and intellectual disability, born from consanguineous Tunisian parents. Exome sequencing and segregation analysis revealed two potentially relevant variants: the NKX2-5 p.Arg25Cys variant (maternally inherited), as well as a single heterozygous TSHR p.Gln90Pro variant (paternally inherited). Of note, a male sibling of the proband, presenting with intellectual disability only, carried the same two variants. No other TSHR variants, or other potentially relevant variants were identified. In this proband, despite the identification of variants in two genes potentially correlated to the phenotype, a definite genetic diagnosis could not be reached. This case report highlights the complexity of exome data interpretation, especially when dealing with families presenting complex phenotypes and variable expression of clinical traits.

A young boy with ventricular arrhythmias and thyroid dysgenesis: two genes are not enough?

Congenital hypothyroidism (CH) may be caused by biallelic variants in the TSHR gene. CH due to thyroid dysgenesis has also been linked to pathogenic variants of the nucleotide kinase 2, homeobox 5 (NKX2-5) gene, which can also cause sudden cardiac death from ventricular arrhythmia. In particular, the NKX2-5 p.Arg25Cys missense variant has been repeatedly reported in patients with congenital heart defects and, more rarely, with hypogonadism. We report the case of a 7 year old boy with ventricular arrhythmias, thyroid dysgenesis and intellectual disability, born from consanguineous Tunisian parents. Exome sequencing and segregation analysis revealed two potentially relevant variants: the NKX2-5 p.Arg25Cys variant (maternally inherited), as well as a single heterozygous TSHR p.Gln90Pro variant (paternally inherited). Of note, a male sibling of the proband, presenting with intellectual disability only, carried the same two variants. No other TSHR variants, or other potentially relevant variants were identified. In this proband, despite the identification of variants in two genes potentially correlated to the phenotype, a definite genetic diagnosis could not be reached. This case report highlights the complexity of exome data interpretation, especially when dealing with families presenting complex phenotypes and variable expression of clinical traits.

Fascial Manipulation Associated With Standard Care Compared to Only Standard Postsurgical Care for Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Postsurgical physiotherapy programs after total hip arthroplasty (THA) show important differences between types and numbers of treatment sessions. To increase functional recovery in postsurgical patients, manual therapy can be added to traditional physiotherapy programs. Fascial manipulation (FM) has been demonstrated to be effective in decreasing pain and increasing muscular capacity. OBJECTIVE: To compare the effectiveness of FM when added to a standard protocol of care. DESIGN: Randomized controlled trial. SETTING: Rehabilitation center. PATIENTS: A total of 51 patients were recruited after total hip arthroplasty. Inclusion criteria were first THA surgery, posterior-lateral access, and onset of pain within a maximum 2 years. Exclusion criteria were previous hip or knee prosthesis, congenital hip dysplasia, elective THA secondary to trauma, real leg-length discrepancy (≥1.5 cm), cognitive impairment, concomitant rheumatic pathology in acute phase, and serious comorbidities such as cardiac, respiratory, and/or neuromuscular pathologies. METHODS: Patients were randomized into 2 groups; both followed a standard protocol based on 2 daily sessions of active exercises for 45 minutes. In the study group, 2 sessions were replaced by FM. The clinical trial was registered at clinicaltrials.gov (NCT02576028). MAIN OUTCOME MEASURES: Functional outcome measures were collected before and after treatment and at the end of the rehabilitation program. The measures included the Harris Hip Score; Timed Up-and-Go test; articular range of motion in abduction, flexion, extension, and bilateral external rotation with heels together; and verbal numerical scale. RESULTS: Statistically significant differences were observed in degrees of flexion between the study and control group with 25.4 (±11.3) and 18.7 (±9.5), respectively (P = .04); for abduction with 16.8 (±7.0) and 11.1 (±6.1), respectively (P = .005); for extension with 16.2 (±4.9) and 9.3 (±3.8), respectively (P = .001); for bilateral external rotation with heels together with 8.3 (±4.3) and 5.5 (±4.6), respectively (P = .04); for the Harris Hip Score 23.3 (±8.9) and 14.5 (±8.5), respectively (P = .002); and for verbal numerical scale score 1.1 (±2.1) and 0.5 (±1.1), respectively. CONCLUSIONS: This study demonstrates that 2 FM sessions are able to significantly improve several functional outcomes in patients compared to usual treatment after THA. LEVEL OF EVIDENCE: II.