# Expanding the phenotypic and immunological landscape of Alazami syndrome: Evidence from seven new patients with LARP7 gene variants

## TL;DR

This study expands the understanding of Alazami syndrome by reporting seven new patients with LARP7 gene variants and identifying new symptoms and immune-related features.

## Contribution

The study reports novel LARP7 gene variants and highlights previously underrecognized immune deficiencies in Alazami syndrome.

## Key findings

- New oro-dental abnormalities and LARP7 gene variants were identified in seven patients.
- Male patients showed signs of primary immunodeficiency, with impaired antibody response to vaccination.
- The study expands the clinical and molecular spectrum of Alazami syndrome.

## Abstract

Alazami syndrome is a neurodevelopmental disorder characterized by postnatal growth retardation, moderate to severe intellectual disability, and facial dysmorphology. It is caused by biallelic variants in the transcriptional regulator La ribonucleoprotein 7 (LARP7), where frameshift variants accounted for the majority of cases. The current study presents 7 new patients, including 3 males and 4 females from 3 unrelated families. Careful and thorough clinical examination identified novel oro-dental disease abnormalities, including a prominent premaxilla and enamel defects. The detected variants (c.1113_1116del, c.997 + 2T > C and c.518T > C) were not reported in the previous studies. The substitution c.518T > C represented the second missense variant to be identified in patients with Alazami syndrome. Male patients from the three families fulfilled ≥ 2 clinical warning signs of primary immunodeficiency. Lymphocyte subset counts and immunoglobulin levels were estimated in patients from two families. The values were within reference ranges, with only minor non-significant alterations in cytotoxic T-cell counts. A functional assay of B lymphocyte response was performed in one family, demonstrating impaired Streptococcus pneumoniae IgG antibody production following Pneumovax vaccination in the male patient, while his female sibling mounted an adequate response. In conclusion, the disease has a wide range of symptoms, which vary greatly among the affected patients. Our study expanded the clinical and molecular spectrum of the disorder and highlighted immunodeficiency as an underrecognized disease feature, potentially with a male sex predilection.

The online version contains supplementary material available at 10.1007/s00431-026-06801-0.