The Long Way to a SHORT Syndrome: A Case Report from the Endocrine-Genetics Clinic

Introduction:
The field of Endocrinology has witnessed a rapid expansion in the taxonomy of monogenic disorders. The following presentation of a rare diagnosis illustrates the complexity of the endocrine genetics field.

Case description:
A 37-year-old patient underwent thyroidectomy and radioiodine treatment due to Papillary thyroid carcinoma. A debilitating myalgia necessitating chronic opioid treatment emerged, with no known etiology despite an extensive evaluation.

Medical History:
Thyroiditis, Dyslipidemia, speech delay, delayed dentition, myopia, diabetes-adult onset, hypogonadism, hearing impairment.

Physical Exam:
Central obesity, short stature (153cm), temporal wasting, gynecomastia

Genetic evaluation:
Muscular disorders gene panel– Negative.

Whole Exome Sequencing (WES) in trio during his daughter`s pregnancy (due to IUGR and shortening of long bones) - Negative.

Revision Analysis of WES Raw Data:
The patient and his daughter were detected with a Heterozygous PIK3R1 c.1712T>C, p.Ile571Thr likely pathogenic variant

Discussion:
Pathogenic variants in the gene PIK3R1 are associated with SHORT syndrome. This syndrome manifests as IUGR, short stature, partial lipodystrophy, insulin resistance, hearing loss and dental issues. An association between pathogenic variants in PIK3R1 and thyroid carcinoma, has been suggested. We present a familial case of the patient and his daughter, that are clinically consistent with SHORT syndrome diagnosis.

Though myalgia is reported as a rare chronic complication of radioiodine treatment, it might be triggered by lipodystrophy.

A molecular diagnosis of SHORT syndrome provides the etiological explanation for this enigmatic manifestation, it explains a multitude of manifestations in the patient and its progeny, influences their follow-up and treatment, and has implications for future pregnancies.