Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder resulting in severe insulin resistance due to defects in signaling through the insulin receptor. Symptoms of RMS include diabetes mellitus due to severe insulin resistance, acanthosis nigricans, impaired adipose tissue, and growth restriction. Herein, we report a case with RMS presenting with acanthosis nigricans due to a novel mutation in the INRS gene.
According to the past medical history, the patient was born with a birth weight of 3500 g. She was the first child of consanguineous parents. On physical examination, her weight was 18.7 kg (-0.08 SDS) and height was 98.7 cm (-2.6 SDS). Initial clinical findings showed severe acanthosis nigricans of the neck, axillae, the external genitalia and antecubital regions, generalized lanugo, abnormalities of the teeth, and dysmorphic face.
Initial laboratory tests showed normal fasting glucose (78 mg/dL), normal postprandial glucose (102 mg/dL), and extremely elevated fasting insulin (129 µIU/mL). After an overnight fast, an oral glucose tolerance test was performed and impaired glucose tolerance was detected. Sequence analysis of the INSR gene in the patient revealed a homozygous missense mutation in exon 11 at the nucleotide position c.861 (c861 C>A) resulting in a premature stop codon instead of tyrosine at codon 287 (p.Y287). Screening of relevant mutation was performed in the remaining family members. The father, mother, and a sibling were heterozygous.
We thought that our patent may have RMS due to her mild clinic signs and a novel mutation in INSR gene detected in molecular analyses.