Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

[pendred syndrome]

Design : Patients with Pendred syndrome have genotypic and phenotypic variability , leading to challenges in definitive diagnosis and deaf children with enlarged vestibular aqueducts are often subjected to repeated investigations when tests for mutations in SLC 26 A 4 are abnormal . This study provides genotype and phenotype information from patients with suspected Pendred syndrome referred to a single clinical endocrinology unit . Methods : Retrospective analysis of 50 patients with suspected Pendred syndrome to investigate the correlation between genetic , perchlorate discharge test (PDT ) and endocrine status . Results : Eight patients with monoallelic mutations had normal PDT . Of the 33 patients with biallelic mutations , 10 of 12 patients with >30 % discharge developed hypothyroidism . In our cohort , c .626 G >T and c .3 -2 A >G result in milder clinical presentations with lower median perchlorate discharge of 9 .3 % (interquartile range 4 -15 %) compared to 40 % (interquartile range 21 -60 %) for the remaining mutations . Eight novel mutations were detected . All patients with PDT <30 % remained euthyroid to date , although the majority are still under age 30 . There was a significant correlation between PDT and size of goitre (R =0 .61 , p =0 .0009 ) and the age of onset of hypothyroidism (R =-0 .62 , p =0 .0297 ). In our population , the hazard of becoming hypothyroid increased by 7 % per percentage point increase in PDT (P <0 .001 ). Conclusion : There is correlation between SLC 26 A 4 genotype and thyroid phenotype . If results hold true for larger patient numbers and longer follow-up , then for patients with monoallelic mutations , PDT could be unnecessary . Patients with biallelic mutations and PDT discharge >30 % have high risk of developing goitre and hypothyroidism , and should have lifelong monitoring .

Diseases
Validation

Diseases presenting "goitre" symptom

cowden syndrome

familial mediterranean fever

pendred syndrome

This symptom has already been validated