Is Pierre Robin syndrome (PRS) genetic?

From the Guidelines

Pierre Robin syndrome (PRS) can have a genetic component, but it is not exclusively genetic, and its causes can be complex and multifactorial. The condition is often associated with various genetic syndromes, such as Stickler syndrome, velocardiofacial syndrome, and Treacher Collins syndrome, which involve specific gene mutations 1. However, PRS can also occur sporadically without an identifiable genetic cause. Key characteristics of PRS include a small lower jaw (micrognathia), backward displacement of the tongue (glossoptosis), and often a cleft palate, which develop as a sequence of events during fetal development.

Some of the genetic disorders that can lead to PRS or similar conditions include mucopolysaccharidoses, which are characterized by enzyme deficiencies leading to defective catabolism of lysosomal glycosaminoglycans and accumulation of mucopolysaccharides in the soft tissues of the body 1. These conditions can cause upper airway narrowing due to hypertrophy of the tongue, tonsils, adenoids, and mucous membranes, which can be worsened by a physiological decrease in tone of the supporting muscles of the pharynx and increased airway resistance.

Given the potential genetic underpinnings of PRS, genetic testing may be recommended to determine if there is an underlying genetic syndrome, especially when PRS is suspected 1. This is crucial because associated genetic conditions may have additional health implications beyond the facial features. Furthermore, family genetic counseling is often beneficial for parents of affected children to understand recurrence risks for future pregnancies, which vary depending on whether the condition is part of a genetic syndrome or occurred sporadically.

In clinical practice, it's essential to approach each case of PRS individually, considering the possibility of underlying genetic causes and the need for comprehensive assessment and management. This includes evaluating for associated conditions that may impact morbidity, mortality, and quality of life, such as sleep-disordered breathing, which can be common in children with craniofacial anomalies, including PRS 1.

From the Research

Genetic Basis of Pierre Robin Syndrome

The question of whether Pierre Robin syndrome (PRS) is genetic can be explored through various studies that have investigated the etiology and pathogenesis of the disease.

• PRS is characterized by a triad of clinical signs: micrognathia, glossoptosis, and obstruction of the upper airways, frequently associated with palatal cleft 2.
• The presence of cleft palate in the grandmother and mother of one patient is seen as evidence in favor of the hereditary transmission of the disease 3.
• Genetic determinants are thought to underlie this functional and morphological entity, based on the existence of Mendelian syndromes with PRS, and the rare observations of familial nonsyndromic PRS 4.
• A review of the phenotypes, developmental basis, and genetics of Pierre Robin complex suggests that a causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated gene expression, precise cellular processes, pathogenesis, and PR-associated anomalies are documented 5.

Evidence of Genetic Association

• The association of PRS with deletion 2q32.3-q33.2 due to an unbalanced reciprocal translocation supports the hypothesis for the genetic bases of nonsyndromic PRS 4.
• The deletion was shown to be flanked by D2S369 (telomeric) and D2S315 (centromeric), thus it maps to a recently determined chromosomal region known to be nonrandomly associated with cleft palate 4.
• Select genes associated with PR are documented, and available animal models could be used to better understand the genetic basis and phenotypic variation of PR 5.

Complexity of the Condition

• PRS is a heterogenic pathological entity and can be found as an isolated disease or in association with other syndromes, with more pronounced symptoms and systemic involvement 2.
• The wide U-shape cleft and airway dysfunction create challenges in clinical management, and disputes exist on the treatment protocol and prognosis of cleft palate management among patients with PRS 6.