Genetic Landscape of Robin Sequence: A Systematic Review

TL;DR

This paper reviews the genetic causes of Robin sequence, a birth condition, and highlights the importance of modern genetic testing for accurate diagnosis and treatment.

Contribution

The paper systematically compiles and differentiates genetic variants associated with isolated and non-isolated Robin sequence.

Findings

Pathogenic variants in genes like SOX9, SNRPB, and COL11A1 are frequently linked to non-isolated Robin sequence.

Common chromosomal deletions in RS include 22q11.2 and 18q.

Whole genome sequencing requires phenotype-driven tools to maximize diagnostic potential in RS.

Abstract

Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction, often occurring with cleft palate and syndromic conditions. The genetic basis of RS is heterogeneous, including monogenic variants and chromosomal rearrangements. This systematic review synthesizes the current genetic landscape of RS, analyzing data from 107 studies that employed various genetic testing methods, including chromosomal microarray (CMA), targeted sequencing, and whole exome sequencing (WES). A distinction is made between genetic variants identified in isolated versus non‐isolated RS. Pathogenic variants in genes as SOX9, SNRPB, SATB2, TGDS, RBM10, COL11A1, and COL2A1 are frequently identified, many of which are linked to non‐isolated RS. The most common chromosomal aberrations are deletions of 22q11.2 and 18q. Up‐to‐date genetic testing is essential to enable accurate diagnosis and personalized clinical care. With the growing use of whole genome sequencing (WGS) in clinical practice, the need for phenotype‐driven interpretation tools is increasing. Some platforms can prioritize gene relevance based on Human Phenotype Ontology (HPO) terms. Documenting both known and novel RS‐associated genes is therefore crucial to fully realize the diagnostic potential of WGS and support evidence‐based clinical decision‐making.

This systematic review summarizes the genetic landscape of Robin sequence (RS), highlighting key differences between isolated and non‐isolated forms and emphasizing the role of up‐to‐date genetic testing for diagnosis and clinical management.

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