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Rabson-Mendenhall syndrome

MedGen UID:
78783
Concept ID:
C0271695
Disease or Syndrome
Synonyms: Mendenhall Syndrome; Pineal hyperplasia AND diabetes mellitus syndrome; Pineal Hyperplasia, Insulin-Resistant Diabetes Mellitus, and Somatic Abnormalities
SNOMED CT: Pineal hyperplasia, insulin-resistant diabetes mellitus and somatic abnormalities (33559001); Pineal hyperplasia AND diabetes mellitus syndrome (33559001); Mendenhall syndrome (33559001); Rabson-Mendenhall syndrome (33559001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): INSR (19p13.2)
 
Monarch Initiative: MONDO:0009874
OMIM®: 262190
Orphanet: ORPHA769

Disease characteristics

INSR-related severe insulin resistance syndrome (INSR-SIRS) comprises a phenotypic spectrum that is a continuum from the severe phenotype of Donohue syndrome to the milder phenotype of Rabson-Mendenhall syndrome (RMS). Donohue syndrome is characterized by severe insulin resistance (hyperinsulinemia with associated fasting hypoglycemia and postprandial hyperglycemia), severe prenatal growth restriction, postnatal growth failure, hypotonia, developmental delay, characteristic facies (proptosis, infraorbital folds, large, low-set, posteriorly rotated ears, thick vermilion of the upper and lower lips, and gingival hypertrophy), and organomegaly involving the heart, kidneys, liver, spleen, and ovaries. Death usually occurs before age one year. RMS, at the milder end of the spectrum, is characterized by severe insulin resistance that, although not as severe as that of Donohue syndrome, is nonetheless accompanied by fluctuations in blood glucose levels, diabetic ketoacidosis, and – in the second decade – microvascular complications. Findings can range from severe growth delay and intellectual disability to normal growth and development. Facial features can be milder than those of Donohue syndrome. Complications of longstanding hyperglycemia are the most common cause of death. While death usually occurs in the second decade, some affected individuals live longer. [from GeneReviews]
Authors:
Aviv Mesika  |  Aharon Klar  |  Tzipora C Falik Zaccai   view full author information

Additional description

From MedlinePlus Genetics
Rabson-Mendenhall syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with Rabson-Mendenhall syndrome, insulin resistance impairs blood glucose regulation and ultimately leads to a condition called diabetes mellitus, in which blood glucose levels can become dangerously high.

Severe insulin resistance in people with Rabson-Mendenhall syndrome affects the development of many parts of the body. Affected individuals are unusually small starting before birth, and infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features of the condition that become apparent early in life include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; dental abnormalities; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Rabson-Mendenhall syndrome include prominent, widely spaced eyes; a broad nose; and large, low-set ears.

Rabson-Mendenhall syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Rabson-Mendenhall syndrome is intermediate in severity between Donohue syndrome (which is usually fatal before age 2) and type A insulin resistance syndrome (which is often not diagnosed until adolescence). People with Rabson-Mendenhall syndrome develop signs and symptoms early in life and live into their teens or twenties. Death usually results from complications related to diabetes mellitus, such as a toxic buildup of acids called ketones in the body (diabetic ketoacidosis).  https://medlineplus.gov/genetics/condition/rabson-mendenhall-syndrome

Clinical features

From HPO
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Long penis
MedGen UID:
82837
Concept ID:
C0269011
Finding
Penile length more than 2 SD above the mean for age.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Diabetic ketoacidosis
MedGen UID:
8351
Concept ID:
C0011880
Disease or Syndrome
A type of diabetic metabolic abnormality with an accumulation of ketone bodies.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Fasting hypoglycemia
MedGen UID:
75765
Concept ID:
C0271708
Disease or Syndrome
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
Insulin-resistant diabetes mellitus
MedGen UID:
163439
Concept ID:
C0854110
Disease or Syndrome
A type of diabetes mellitus related not to lack of insulin but rather to lack of response to insulin on the part of the target tissues of insulin such as muscle, fat, and liver cells. This type of diabetes is typically associated with increases both in blood glucose concentrations as well as in fasting and postprandial serum insulin levels.
Postprandial hyperglycemia
MedGen UID:
383702
Concept ID:
C1855520
Finding
An increased concentration of glucose in the blood following a meal.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Advanced eruption of teeth
MedGen UID:
78588
Concept ID:
C0266054
Finding
Premature tooth eruption, which can be defined as tooth eruption more than 2 SD earlier than the mean eruption age.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Hypertrichosis
MedGen UID:
43787
Concept ID:
C0020555
Disease or Syndrome
Hypertrichosis is increased hair growth that is abnormal in quantity or location.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Onychauxis
MedGen UID:
78098
Concept ID:
C0263536
Disease or Syndrome
Thickened nails without deformity.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
An increased concentration of insulin in the blood.
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRabson-Mendenhall syndrome
Follow this link to review classifications for Rabson-Mendenhall syndrome in Orphanet.

Professional guidelines

PubMed

Al-Kandari H, Al-Abdulrazzaq D, Al-Jaser F, Al-Mulla F, Davidsson L
Prim Care Diabetes 2021 Feb;15(1):175-177. Epub 2020 Aug 23 doi: 10.1016/j.pcd.2020.07.012. PMID: 32843252
Paz-Filho G, Mastronardi CA, Licinio J
Metabolism 2015 Jan;64(1):146-56. Epub 2014 Aug 3 doi: 10.1016/j.metabol.2014.07.014. PMID: 25156686
McDonald A, Williams RM, Regan FM, Semple RK, Dunger DB
Eur J Endocrinol 2007 Aug;157 Suppl 1:S51-6. doi: 10.1530/EJE-07-0271. PMID: 17785698

Recent clinical studies

Etiology

Okawa MC, Cochran E, Lightbourne M, Brown RJ
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782. PMID: 34718628Free PMC Article
Al-Kandari H, Al-Abdulrazzaq D, Al-Jaser F, Al-Mulla F, Davidsson L
Prim Care Diabetes 2021 Feb;15(1):175-177. Epub 2020 Aug 23 doi: 10.1016/j.pcd.2020.07.012. PMID: 32843252
Brown RJ, Cochran E, Gorden P
J Clin Endocrinol Metab 2013 Nov;98(11):E1749-56. Epub 2013 Aug 22 doi: 10.1210/jc.2013-2317. PMID: 23969187Free PMC Article
Parveen BA, Sindhuja R
Int J Dermatol 2008 Aug;47(8):839-41. doi: 10.1111/j.1365-4632.2008.03591.x. PMID: 18717867
Musso C, Cochran E, Moran SA, Skarulis MC, Oral EA, Taylor S, Gorden P
Medicine (Baltimore) 2004 Jul;83(4):209-222. doi: 10.1097/01.md.0000133625.73570.54. PMID: 15232309

Diagnosis

Rojek A, Wikiera B, Noczynska A, Niedziela M
J Clin Res Pediatr Endocrinol 2023 Aug 23;15(3):312-317. Epub 2021 Dec 30 doi: 10.4274/jcrpe.galenos.2021.2021.0256. PMID: 34965699Free PMC Article
Laimon W, El-Ziny M, El-Hawary A, Elsharkawy A, Salem NA, Aboelenin HM, Awad MH, Flanagan SE, De Franco E
Acta Diabetol 2021 Dec;58(12):1689-1700. Epub 2021 Aug 23 doi: 10.1007/s00592-021-01788-6. PMID: 34426871
Al-Kandari H, Al-Abdulrazzaq D, Al-Jaser F, Al-Mulla F, Davidsson L
Prim Care Diabetes 2021 Feb;15(1):175-177. Epub 2020 Aug 23 doi: 10.1016/j.pcd.2020.07.012. PMID: 32843252
Gupta J, Daniel JM, Vasudevan V
J Indian Soc Pedod Prev Dent 2012 Jul-Sep;30(3):279-82. doi: 10.4103/0970-4388.105026. PMID: 23263437
Parveen BA, Sindhuja R
Int J Dermatol 2008 Aug;47(8):839-41. doi: 10.1111/j.1365-4632.2008.03591.x. PMID: 18717867

Therapy

Galderisi A, Tamborlane W, Taylor SI, Attia N, Moretti C, Barbetti F
Pediatrics 2022 Jul 1;150(1) doi: 10.1542/peds.2021-055671. PMID: 35652305
Okawa MC, Cochran E, Lightbourne M, Brown RJ
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782. PMID: 34718628Free PMC Article
Paz-Filho G, Mastronardi CA, Licinio J
Metabolism 2015 Jan;64(1):146-56. Epub 2014 Aug 3 doi: 10.1016/j.metabol.2014.07.014. PMID: 25156686
McDonald A, Williams RM, Regan FM, Semple RK, Dunger DB
Eur J Endocrinol 2007 Aug;157 Suppl 1:S51-6. doi: 10.1530/EJE-07-0271. PMID: 17785698
Cochran E, Young JR, Sebring N, DePaoli A, Oral EA, Gorden P
J Clin Endocrinol Metab 2004 Apr;89(4):1548-54. doi: 10.1210/jc.2003-031952. PMID: 15070911

Prognosis

Okawa MC, Cochran E, Lightbourne M, Brown RJ
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782. PMID: 34718628Free PMC Article
Laimon W, El-Ziny M, El-Hawary A, Elsharkawy A, Salem NA, Aboelenin HM, Awad MH, Flanagan SE, De Franco E
Acta Diabetol 2021 Dec;58(12):1689-1700. Epub 2021 Aug 23 doi: 10.1007/s00592-021-01788-6. PMID: 34426871
Zhou Q, Yu J, Yuan X, Wang C, Zhu Z, Zhang A, Gu W
Front Endocrinol (Lausanne) 2021;12:606964. Epub 2021 Apr 29 doi: 10.3389/fendo.2021.606964. PMID: 33995269Free PMC Article
Al-Kandari H, Al-Abdulrazzaq D, Al-Jaser F, Al-Mulla F, Davidsson L
Prim Care Diabetes 2021 Feb;15(1):175-177. Epub 2020 Aug 23 doi: 10.1016/j.pcd.2020.07.012. PMID: 32843252
Parveen BA, Sindhuja R
Int J Dermatol 2008 Aug;47(8):839-41. doi: 10.1111/j.1365-4632.2008.03591.x. PMID: 18717867

Clinical prediction guides

Rojek A, Wikiera B, Noczynska A, Niedziela M
J Clin Res Pediatr Endocrinol 2023 Aug 23;15(3):312-317. Epub 2021 Dec 30 doi: 10.4274/jcrpe.galenos.2021.2021.0256. PMID: 34965699Free PMC Article
Okawa MC, Cochran E, Lightbourne M, Brown RJ
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782. PMID: 34718628Free PMC Article
Paz-Filho G, Mastronardi CA, Licinio J
Metabolism 2015 Jan;64(1):146-56. Epub 2014 Aug 3 doi: 10.1016/j.metabol.2014.07.014. PMID: 25156686
Brown RJ, Cochran E, Gorden P
J Clin Endocrinol Metab 2013 Nov;98(11):E1749-56. Epub 2013 Aug 22 doi: 10.1210/jc.2013-2317. PMID: 23969187Free PMC Article
McDonald A, Williams RM, Regan FM, Semple RK, Dunger DB
Eur J Endocrinol 2007 Aug;157 Suppl 1:S51-6. doi: 10.1530/EJE-07-0271. PMID: 17785698

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