ESPE Abstracts

Background: Branchio-oto-renal (BOR) syndrome is a rare inheritable condition affecting the ears, 2nd branchial arch structures and the urinary system. Recognised features include hearing loss, structural defects of the ear, branchial defects, and a variety of renal malformations. Causative genetic variants have been identified as SIX1 and EYA1, accounting for approximately 49% of all cases of BOR syndrome. Short stature has not commonly been described in BOR syndrome, but is associated with oculo-facial-cervical syndrome and oculoauriculovertebral syndrome, which have demonstrated allelism with BOR due to mutations involving the EYA1 gene.

Methods: We present growth data from two unrelated pedigrees with confirmed clinical diagnosis of branchio-oto-renal syndrome based on published criteria (Chang, 2004). The first pedigree consists of four siblings (one girl, three boys) and the second of three siblings (two girls, one boy), all aged between 7 to 24 years. Four of the cohort have reached a final height ranging from <3rd to 10th centile with a mid-parental height n prediction of the 25th centile in both families. Growth measurements available for the 7 children show normal pre-natal and post-natal growth, marked delay in bone age, and a definite fall off in height velocity from the mid childhood years. None have sufficient renal involvement (normal creatinine levels) to account for their poor growth. Two individuals, from separate families, have met the criteria for growth hormone deficiency and have shown a response to GH replacement. Growth factor measurements (IGF-1, IGFBP3) are non-discriminatory for growth in these pedigrees.

Discussion: Short stature and growth hormone deficiency are not recognised features of branchio-oto-renal syndrome but these two family cohorts show a similar pattern of growth, with low height velocity, falling below their centiles in later childhood and failure to reach the predicted mid-parental height suggestive of suboptimal late childhood and pubertal growth. The aetiology for this finding remains unclear. Genetic analysis is in process but the yield for positive mutations in BOR syndrome is low. As an extension of this review we are pursuing auxology data on other families with this rare syndrome to expand on this unusual phenotype in an effort to identify unelucidated factors contributing to reduced growth. Growth surveillance is advocated in children with this condition. Normal growth and centiles in the early childhood years do not guarantee final height attainment.

References: Chang, E. H. Branchio-oto-renal syndrome: The mutation spectrum in EYA1 and its phenotypic consequences. Human Mutat 2004;23: 582–589.