Rabson–Mendenhall syndrome with recurrent cerebral infarcts caused by a novel <i>INSR</i> mutation

Mohanan, Saritha; Chandrashekar, Laxmisha; Semple, Robert K.; Thappa, Devinder Mohan; Parameswaran, Narayanan; Negi, Vir Singh; Ramassamy, Sivaranjini

doi:10.1111/j.1365-4632.2012.05665.x

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…An exhaustive literature survey revealed that this will be the first genetically confirmed published case of RMS with the genetic mutation p. Ile348Phe. A similar amino acid conversion was observed in another reported case of RMS, but situated 27 amino acids away from the mutation reported in our patient, hence the mutation in our patient is unique and novel [12]. …”

Section: Discussionsupporting

confidence: 86%

“…For confirmation of the diagnosis of RMS, he underwent genetic analysis which revealed a novel homozygous variant in the INSR gene, NM_000208.2:c.1042A > T (p. Ile348Phe). Various INSR mutations have been reported previously in patients with RMS (Table 2) [12]. An exhaustive literature survey revealed that this will be the first genetically confirmed published case of RMS with the genetic mutation p. Ile348Phe.…”

Section: Discussionmentioning

confidence: 68%

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Rabson Mendenhall Syndrome caused by a novel missense mutation

Sinnarajah¹,

Dayasiri²,

Dissanayake³

et al. 2016

Int J Pediatr Endocrinol

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BackgroundRabson Mendenhall syndrome is a rare endocrine condition characterized by severe insulin resistance and hyperglycemia. It occurs due to mutations in the insulin receptor gene. Few mutations which are associated with Rabson Mendenhall syndrome have been identified and reported in the past. The management of this condition is extremely challenging and will need multi-disciplinary approach.Case presentationAn 11 year old boy presented with polyuria and polydipsia. He was noted to have coarse facies, severe acanthosis nigricans, hypertrichosis, retarded growth and developmental delay. Investigations revealed severe hyperglycemia which was poorly responsive to high doses of insulin. A diagnosis of Rabson Mendenhall syndrome was suspected based on his physical characteristics in the presence of insulin resistance. Genetic studies revealed a homozygous missense mutation in the Insulin receptor gene confirming the diagnosis of Rabson Mendenhall syndrome. This is a novel mutation which has not been reported previously.ConclusionRabson Mendenhall syndrome should be suspected in a patient with characteristic physical features, severe hyperglycemia and insulin resistance. The genetic studies will not only confirm the diagnosis but also will help in counselling. Wider collaboration is needed to identify definitive treatment options for managing this rare condition.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 68%

Rabson Mendenhall Syndrome caused by a novel missense mutation

Sinnarajah¹,

Dayasiri²,

Dissanayake³

et al. 2016

Int J Pediatr Endocrinol

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“…The combination of two insulin sensitizers (metformin and glitazone) is a well-known and validated therapy in patients with type 2 diabetes [17,21,22]. Patients with RMS have been treated with high doses of insulin and insulin sensitizing drugs [4,5,10,23]. The introduction of multi drug therapy especially in the early phase might improve glycemic control, allows the use of lower doses of insulin and delay microvascular complications [23].…”

Section: Discussionmentioning

confidence: 99%

Rabson Mendenhall Syndrome; a Case Report and Review of Literature

Zamanfa¹,

Mohamadi²,

Maskopaii³

2020

IJEC

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Genetic disease is caused by a gene change. Genetic disease is one of the types of diseases affecting the personal, family and social life. One of the types of genetic disease is Rabson Mendenhall Syndrome. The Rabson Mendenhall Syndrome (RMS) was first described by Rabson and Menden-hall in 1956. Rabson Mendenhall syndrome is an extremely rare genetic disorder with autosomal recessive inheritance of unknown prevalence that is estimated to affect less than 1 per million people worldwide characterized by severe insulin resistance. The present study is a case report of a patient with Rabson Mendenhall Syndrome in Iran. A 6 year old girl presented with severe hyperglycemia and loss of consciousness and acidosis. In spite of taking large doses of insulin, her sugars were uncontrolled. She had severe acanthosis nigricans. There was associated growth retardation, dental dysplasia, distent abdomen, emaciated extremities and clitoromegaly. In last admission with diabetic ketoacidosis she was treated with intravenous fluids, insulin drip, metformin and also pioglitazone, antibiotics and other supportive treatments as needed, but unfortunately after few days this treatments could not save her and patient expired. There is no complete cure for the condition and the current treatments are difficult and not very promising.

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“…Donohue syndrome and Rabson–Mendenhall syndrome are historical terms that predate the advent of genetic testing and represent opposite ends of clinical spectrum of disease caused by biallelic deleterious INSR mutations. In the more severe, autosomal recessive receptoropathies, hyperinsulinaemia and dysglycaemia are accompanied by linear growth retardation, overgrowth of many soft tissues, and significant reduction in life expectancy due to complications including infections, intractable ketosis, heart failure, cerebral infarcts and ovarian tumours .…”

Section: Discussionmentioning

confidence: 99%

Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation

et al. 2016

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Background Congenital insulin resistance syndromes are caused by biallelic mutations within the insulin receptor gene (INSR). Recombinant human insulin-like growth factor (rhIGF1) has been used with mixed success, however rigorous assessment of its efficacy is lacking. Here, we describe a child with a homozygous mutation in INSR successfully treated with rhIGF1 for more than 5 years. Case report The patient presented with osmotic diabetes symptoms and was noted to have dysplastic dentition, hypertrichosis, coarse and dysmorphic facial features. Acanthosis nigricans, skin tags and rugated hyperkeratosis were also evident on the posterior neck, axilla and groin. A homozygous INSR essential splice site mutation (c.1268+2T>C, p.G374fs*12) was identified, for which both parents were found to be heterozygous. The patient was treated with twice daily injections of rhIGF1 and metformin for more than 5 years with improvement in her acanthosis nigricans, hyperkeratosis and hypertrichosis. A dramatic fall in fasting insulin, HOMA-IR and HbA1c has been maintained over the entire course of treatment without adverse effects. Her linear growth velocity has remained on target for her predicted adult height. Discussion Our case demonstrates the effectiveness of rhIGF1 as an early treatment in a patient with a biallelic mutation within INSR without evidence of fluid retention, retinopathy, muscle pain, heart failure, cerebral infarcts or benign intracranial hypertension. Her case suggests rhIGF1 can and should be considered as an initial treatment option instead of as a final option in those with INSR mutations.

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Rabson–Mendenhall syndrome with recurrent cerebral infarcts caused by a novel INSR mutation

Cited by 8 publications

References 19 publications

Rabson Mendenhall Syndrome caused by a novel missense mutation

Rabson Mendenhall Syndrome caused by a novel missense mutation

Rabson Mendenhall Syndrome; a Case Report and Review of Literature

Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation

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