Khdir H. Hamad, Sadraldin A. Braim, Dyari Q. Hamad, Araz Q. Abdalla, Maria A. Rasool, Galawezh R. Hamad, Karukh K. Mohammed, Barham H. Bapir and 2 more
Introduction Pilarowski–Bjornsson syndrome (PILBOS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous variants in chromodomain helicase DNA-binding protein 1 (CHD1), a gene encoding an adenosine triphosphate (ATP)-dependent chromatin remodeler. Since its initial description in 2018, only…
Pilarowski–Bjornsson Syndrome with Congenital Heart Defect: A Case Report and Literature Review
Khdir H. Hamad, Sadraldin A. Braim, Dyari Q. Hamad, Araz Q. Abdalla, Maria A. Rasool, Galawezh R. Hamad, Karukh K. Mohammed, Barham H. Bapir and 2 more
IntroductionPilarowski–Bjornsson syndrome (PILBOS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous variants in chromodomain helicase DNA-binding protein 1 (CHD1), a gene encoding an adenosine triphosphate (ATP)-dependent chromatin remodeler. Since its initial description in 2018, only a limited number of cases have been reported in the literature.
Case PresentationA 4-month-old male infant presented with persistent hypotonia and recurrent focal seizures beginning in the neonatal period, accompanied by severe global developmental delay. Brain magnetic resonance imaging (MRI) was structurally normal. Whole exome sequencing identified a heterozygous de novo CHD1 variant (NM_001270.4: c.797C>T; p.Pro266Leu), classified as a variant of uncertain significance. Echocardiography revealed a medium-sized secundum atrial septal defect with right-sided chamber dilatation. The clinical course was complicated by recurrent lower respiratory tract infections and progressive respiratory distress.
Literature ReviewReview of eight previously reported cases confirms global developmental delay and hypotonia as universal features of PILBOS (8/8, 100%). Dysmorphic craniofacial findings were present in 7/8 (87.5%) cases, and seizures occurred in 3/8 (37.5%). Intellectual disability was confirmed in 3/8 (37.5%) and not assessable in a further 3/8 (37.5%). Respiratory complications were documented in 1/8 (12.5%) cases. De novo inheritance was confirmed in 4/8 (50%) cases. No structural cardiac defects have been documented in any previously reported case, and all 8/8 (100%) patients were alive at last follow-up.
ConclusionFindings from this case suggest that structural congenital heart defects may represent an underrecognized component of the PILBOS phenotypic spectrum. Further case reports and functional investigations are required to establish whether cardiac involvement constitutes a consistent feature of CHD1-related disease.
Rebaz M. Ali, Karukh K. Mohammed, Sasan M. Ahmed, Kayhan A. Najar, Mohammed Q. Mustafa, Zanyar K. Hama, Shadan A. Hamad, Maria A. Rasool and 4 more
Introduction Tarlatamab is a Delta-like ligand 3 (DLL3) -directed bispecific T-cell engager recently approved for use in patients with advanced small cell lung cancer (SCLC) after progression on platinum-based therapy. This meta-analysis evaluated the efficacy and safety of tarlatamab as monotherapy and in combination…
Small Cell Lung Cancer and Tarlatamab: A Meta-Analysis of Clinical Trials
Rebaz M. Ali, Karukh K. Mohammed, Sasan M. Ahmed, Kayhan A. Najar, Mohammed Q. Mustafa, Zanyar K. Hama, Shadan A. Hamad, Maria A. Rasool and 4 more
IntroductionTarlatamab is a Delta-like ligand 3 (DLL3) -directed bispecific T-cell engager recently approved for use in patients with advanced small cell lung cancer (SCLC) after progression on platinum-based therapy. This meta-analysis evaluated the efficacy and safety of tarlatamab as monotherapy and in combination regimens in the treatment of SCLC.
MethodsA systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE and EMBASE were searched from inception through September 2025 to identify clinical trials evaluating tarlatamab in SCLC. Eligible studies reported quantifiable efficacy and/or safety outcomes. Random-effects models were used to pool objective response rate (ORR) and disease control rate (DCR), and Kaplan–Meier methods were applied to assess survival outcomes.
ResultsSeven clinical trials involving 1,247 patients with advanced SCLC were included. The pooled ORR was 0.42 (95% CI 0.31–0.54), with response rates ranging from 21–47% in monotherapy studies and up to 48% in combination regimens. Across six studies, pooled DCR was 0.48 (95% CI 0.31–0.66), with DCR reaching up to 87% in combination settings. Median progression-free survival ranged from 3.5 to 5.6 months, while median overall survival ranged from 13.2 to 25.3 months. Pooled time-to-event analyses demonstrated significant reductions in the risk of disease progression and death. Grade 3 and grade 4 adverse events occurred in 5.4% and 1.4% of patients, respectively, although safety reporting was incomplete in several studies.
ConclusionTarlatamab demonstrates clinically meaningful antitumor activity with an acceptable safety profile in heavily pretreated SCLC. These findings support DLL3-targeted therapy as a promising treatment strategy and warrant further prospective studies to define its optimal role in the evolving SCLC treatment landscape.
