Pendreds syndrome: genetics and phenotypic variability
M. Alves, M. Bastos, A. Vieira, S. Gouveia, J. Saraiva, C. Moreno & M. Carvalheiro
Background: Pendred syndrome (PS) is an autosomal recessive disorder characterized by defective organification of iodine, goiter and deafness. It is caused by mutations in pendrin gene (SLC26A4), a transporter of chloride/iodide that mediates the efflux of iodine from thyroid follicular cells to the follicular lumen.
Clinical case: Case-index: MJFS, female, refered to consultation at 35 years for enlarged neck. Personal history: congenital deafness, thyroidectomy at age 19, under levothyroxine therapy. Family history: deafness and goiter in several family members. Physical examination: goiter. Evaluation: normal thyroid function; thyroid hypertrophy with bilateral homogeneous hyperfixation in cintigraphy. Clinical evolution: at 55 years presented a nodule in the right lobe with cytology suspicion of papillary carcinoma; underwent right lobectomy with isthmectomy. The histology revealed a microfolicular adenoma, nodular hyperplasia and papillary hyperplasia. At 63 years presented left lobe enlargement, with suspicious nodule. The cytology was benign (colloid). The molecular study of SLC26A4 gene was performed and revealed mutations c.367C>T (p.Pro123Ser) and c.412G>T (p.Val138Phe), in heterozygosity in exon 4, confirming the diagnosis of PS.
The daughter of case-index: MSF, female, consultation at 3 years for enlarged neck. Personal history: congenital deafness. Evaluation: diffuse goiter without thyroid dysfunction, autoimmunity negative. Evolution: at 11 old years presented thyroid enlargement; levothyroxine therapy was initiated. At 18 years had a multinodular goiter. At 22 years had complains of pain and cervical compression; the cytology was colloid. A total thyroidectomy was performed. Histology: diffuse hyperplasia without malignancy. The molecular study of SLC26A4 gene revealed mutation c.367C> T (p.Pro123Ser), in homozygosity in exon 4, confirming the diagnosis of PS.
The husband of index case, without genetic relashionship, but also with goiter and neurosensorial deafness, as well as other family members, waits for genetic study.
Conclusions: The association of familial goiter and congenital deafness should cause suspicion of this entity. Although thyroid function isnt usually affected, the structural change is often significant, putting difficulties in differential diagnosis. The diagnosis is confirmed by molecular studies, which must be performed in all family members.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.