Insights from European Reference Network for rare neurological disorders study surveys on diagnosis, treatment, and management of NKX2-1-related disorders

Eur J Paediatr Neurol. 2024 Jul:51:110-117. doi: 10.1016/j.ejpn.2024.06.007. Epub 2024 Jun 19.

Abstract

Background: NKX2-1-related disorder (NKX2-1-RD) is a rare disease characterized by a triad of primary hypothyroidism, neonatal respiratory distress, and neurological features, including chorea.

Objective: This study aimed to identify discrepancies in the management of NKX2-1-RD among European Union (EU) specialists.

Methods: The ERN-RND Chorea & Huntington disease group designed a survey to conduct a cross-sectional multicenter study on the management of NKX2-1-RD. Descriptive analysis was performed, and total responses are presented for each item.

Results: The study involved 23 experts from 13 EU countries with experience in evaluating hyperkinetic patients with NKX2-1-RD: 11 were adult specialists, and 12 were pediatric specialists. NKX2-1-RD diagnosis was made at different ages, with the most common initial symptoms being hypotonia and/or motor developmental delay (reported by 11 experts) and chorea (reported by 8 experts). Chorea involved various body parts and showed improvement as reported by 9 experts, stabilization by 12 experts, and worsening by 2 experts with age. The pharmacological treatment of chorea varied widely among the experts. Misdiagnosis was reported by 14 experts. NKX2-1 pathogenic variants or deletions were confirmed in >75 % of patients (reported by 12 experts). Pulmonary and endocrinology evaluations were requested by 7 and 12 experts, respectively. The management of psychiatric comorbidities also varied among the different experts.

Conclusions: This study highlights the need for a clinical practice guideline for the management of NKX2-1-RD to ensure that patients across the EU receive consistent and appropriate care. Such a guideline would benefit both doctors and healthcare practitioners.

Keywords: Chorea; NKX2-1.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Athetosis / diagnosis
  • Child
  • Chorea* / diagnosis
  • Chorea* / drug therapy
  • Chorea* / genetics
  • Chorea* / therapy
  • Congenital Hypothyroidism / diagnosis
  • Congenital Hypothyroidism / drug therapy
  • Congenital Hypothyroidism / therapy
  • Cross-Sectional Studies
  • Europe
  • European Union
  • Humans
  • Male
  • Rare Diseases* / diagnosis
  • Rare Diseases* / therapy
  • Respiratory Distress Syndrome, Newborn / diagnosis
  • Respiratory Distress Syndrome, Newborn / therapy
  • Surveys and Questionnaires
  • Thyroid Nuclear Factor 1 / genetics

Substances

  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1

Supplementary concepts

  • Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress