A Rare De Novo TUBB2A Variant (p.Arg2His) Associated with Microcephaly, Refractory Epilepsy, and Growth Hormone-Responsive Short Stature
Acta Cytologica, ss.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1159/msy/adrag012
- Dergi Adı: Acta Cytologica
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
- Sayfa Sayıları: ss.1
- Anahtar Kelimeler: Epilepsy, Malformation of cortical development, Somatotropin treatment, TUBB2A, Tubulinopathy
- Gazi Üniversitesi Adresli: Evet
Özet
Introduction: Tubulinopathies are a group of rare neurological disorders arising from pathogenic variants in genes encoding α- and β-tubulin isoforms, disrupting neuronal migration and cortical organization. TUBB2A variants are exceptionally rare, with a limited number of cases documented globally. Case Presentation: We present an 11-year-old male with a de novo heterozygous TUBB2A variant (NM_001069.3:c.5G>A; p.Arg2His), identified by clinical exome sequencing. His clinical features comprised congenital microcephaly, global developmental delay, and medically refractory infantile-onset epilepsy, including a severe episode of status epilepticus requiring intensive care unit admission. Neuroimaging demonstrated hypoplasia of the corpus callosum, bilateral frontal pachygyria-dysgyria, and asymmetric mild dilatation of the left lateral ventricle. The patient additionally exhibited significant growth failure (height −2.31 SDS at age 6.11 years). Despite normal peak growth hormone (GH) levels on clonidine stimulation testing (11.6 ng/mL), a therapeutic trial of somatotropin (40 μg/kg/day) was initiated for severe non-GHD growth failure. A robust auxological response was observed over 3.2 years of treatment, improving height SDS from −2.31 to −0.23 at completion of therapy (age 9.31 years; height 132.5 cm). Following cessation, growth velocity declined markedly to approximately 2.1 cm/year over 20 months. At most recent assessment (age 11 years), height was 136 cm (−1.22 SDS), weight 24.7 kg (−2.31 SDS), and BMI 13.35 kg/m2 (−2.43 SDS). Conclusion: This report expands the clinical database of TUBB2A-related tubulinopathy and provides preliminary evidence supporting somatotropin as a potential intervention for associated growth failure in selected patients. However, therapeutic decisions must balance expected auxological benefits against health-economic constraints, post-treatment growth deceleration, and potential long-term safety risks.