Rabson-Mendenhall syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: Mendenhall syndrome
Pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities
Number of Symptoms 99
OrphanetNr: 769
OMIM Id: 262190
ICD-10: E13
UMLs: C0271695
MeSH: D056731
MedDRA:
Snomed: 33559001

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
2573522 [IBIS]
Age of onset: Neonatal
Infancy
13302174 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Hypertrichosis
 -Rare genetic disease
 -Rare skin disease
Insulin-resistance syndrome
 -Rare endocrine disease
 -Rare genetic disease

Comment:

Rabson-Mendenhall syndrome is a monogenic form of diabetes caused by mutations in INSR (PMID:21127150). First described by Rabson and Mendenhall in 1956 in three siblings presenting with dental and skin abnormalities, abdominal distension, coarse facies, early dentition, hirsutism, phallic enlargement and pineal hyperplasia, Rabson-Mendenhall syndrome (RMS) is a rare insulin resistance syndrome of unknown prevalence. It is inherited as autosomal recessive trait with variable expressivity. There is paradoxical fasting hypoglycemia and post-prandial hyperglycemia initially in life, followed by constant hyperglycemia (by 4 years of age) and constant ketoacidosis by 6 years of age. Although insulin levels are extremely elevated initially and then decrease with age, they remain higher than normal (PMID:25484423).

Symptom Information: Sort by abundance 

1
 (HPO:0001538) Protuberant abdomen 13302174; 1190820; 3415309; 20155514 IBIS 36 / 7739
2
 (HPO:0001090) Large eyes 3415309 IBIS 20 / 7739
3
 (HPO:0001941) Acidosis 13302174 IBIS 9 / 7739
4
 (HPO:0001993) Ketoacidosis 13302174; 25484423; 12023989 IBIS 17 / 7739
5
 (HPO:0001953) Diabetic ketoacidosis 1190820 IBIS 6 / 7739
6
 (HPO:0007485) Absence of subcutaneous fat Frequent [IBIS] 1190820; 25484423 IBIS 6 / 7739
7
 (HPO:0004322) Short stature Frequent [IBIS] Frequent [Orphanet] 13302174; 1190820; 12023989 IBIS 1232 / 7739
8
 (HPO:0001518) Small for gestational age Frequent [IBIS] 1190820; 3415309; 12023989 IBIS 107 / 7739
9
 (HPO:0011014) Abnormal glucose homeostasis Frequent [IBIS] 25484423 IBIS 5 / 7739
10
 (HPO:0003074) Hyperglycemia 13302174 IBIS 37 / 7739
11
 (HPO:0011998) Postprandial hyperglycemia 25484423 IBIS 5 / 7739
12
 (HPO:0001943) Hypoglycemia 3415309 IBIS 131 / 7739
13
 (HPO:0003076) Glycosuria 13302174; 1190820; 3415309; 25484423 IBIS 32 / 7739
14
 (HPO:0000842) Hyperinsulinemia Frequent [IBIS] 1190820; 3415309; 25484423; 20155514 IBIS 39 / 7739
15
 (HPO:0000855) Insulin resistance 13302174; 2573522; 20155514 IBIS 32 / 7739
16
 (HPO:0000831) Insulin-resistant diabetes mellitus 13302174; 2573522; 1190820; 20155514 IBIS 22 / 7739
17
 (HPO:0003355) Aminoaciduria 1190820 IBIS 65 / 7739
18
 (HPO:0003162) Fasting hypoglycemia 25484423 IBIS 8 / 7739
19
 (HPO:0000403) Recurrent otitis media 12023989 IBIS 61 / 7739
20
 (MedDRA:10034531) Perinephric abscess 13302174 IBIS 1 / 7739
21
 (HPO:0012330) Pyelonephritis 13302174 IBIS 7 / 7739
22
 (HPO:0100577) Urinary bladder inflammation 13302174 IBIS 4 / 7739
23
 (HPO:0100806) Sepsis 13302174; 1190820 IBIS 48 / 7739
24
 (HPO:0002900) Hypokalemia 1190820 IBIS 45 / 7739
25
 (HPO:0011342) Mild global developmental delay 12023989 IBIS 10 / 7739
26
 (HPO:0001959) Polydipsia 13302174; 1190820; 25484423 IBIS 43 / 7739
27
 (HPO:0002315) Headache 13302174 IBIS 175 / 7739
28
 (HPO:0001511) Intrauterine growth retardation Very frequent [Orphanet] 25484423 IBIS 358 / 7739
29
 (HPO:0001562) Oligohydramnios 12023989 IBIS 75 / 7739
30
 (HPO:0009381) Short finger Frequent [Orphanet] 3415309; 12023989 IBIS 45 / 7739
31
 (HPO:0000303) Mandibular prognathia Very frequent [Orphanet] 13302174; 3415309; 25484423 IBIS 179 / 7739
32
 (HPO:0010758) Abnormality of the premaxilla 20155514 IBIS 1 / 7739
33
 (HPO:0011220) Prominent forehead 13302174 IBIS 137 / 7739
34
 (HPO:0100769) Synovitis 12023989 IBIS 86 / 7739
35
 (HPO:0100874) Thick hair Frequent [Orphanet] 13302174 IBIS 7 / 7739
36
 (HPO:0000574) Thick eyebrow 20155514 IBIS 96 / 7739
37
 (HPO:0002230) Generalized hirsutism Very frequent [Orphanet] 13302174; 20155514 IBIS 32 / 7739
38
 (HPO:0004554) Generalized hypertrichosis Very frequent [Orphanet] 25484423 IBIS 30 / 7739
39
 (HPO:0001007) Hirsutism Frequent [IBIS] Very frequent [Orphanet] 1190820; 25484423; 12023989 IBIS 91 / 7739
40
 (HPO:0000998) Hypertrichosis Very frequent [Orphanet] 13302174; 25484423 IBIS 52 / 7739
41
 (HPO:0002216) Premature graying of hair 25484423 IBIS 43 / 7739
42
 (HPO:0001805) Thick nail Very frequent [Orphanet] 13302174; 1190820 IBIS 96 / 7739
43
 (HPO:0012094) Abnormal pancreas size 13302174 IBIS 5 / 7739
44
 (HPO:0100732) Pancreatic fibrosis 13302174 IBIS 12 / 7739
45
 (HPO:0008221) Adrenal hyperplasia 13302174; 20155514 IBIS 24 / 7739
46
 (HPO:0000859) Hyperaldosteronism 20155514 IBIS 17 / 7739
47
 (HPO:0000055) Abnormality of female external genitalia 13302174 IBIS 5 / 7739
48
 (HPO:0008665) Clitoral hypertrophy 13302174 IBIS 10 / 7739
49
 (HPO:0000057) Clitoromegaly 1190820; 25484423; 20155514; 12023989 IBIS 30 / 7739
50
 (HPO:0000065) Labial hypertrophy 13302174 IBIS 4 / 7739
51
 (HPO:0000059) Hypoplastic labia majora 20155514 IBIS 22 / 7739
52
 (HPO:0000040) Long penis Very frequent [Orphanet] 13302174; 1190820; 3415309; 12023989 IBIS 17 / 7739
53
 (HPO:0003247) Overgrowth of external genitalia Frequent [IBIS] 13302174; 1190820; 25484423 IBIS 3 / 7739
54
 (HPO:0000138) Ovarian cyst Occasional [Orphanet] occasional [HPO] 1190820 IBIS 25 / 7739
55
 (HPO:0100615) Ovarian neoplasm 13302174 IBIS 25 / 7739
56
 (HPO:0000147) Polycystic ovaries Occasional [Orphanet] 25484423; 20155514 IBIS 18 / 7739
57
 (HPO:0001999) Abnormal facial shape Frequent [IBIS] 1190820; 3415309 IBIS 169 / 7739
58
 (HPO:0000280) Coarse facial features Very frequent [Orphanet] 13302174; 3415309; 25484423; 20155514; 12023989 IBIS 189 / 7739
59
 (HPO:0000689) Dental malocclusion 20155514 IBIS 114 / 7739
60
 (HPO:0012471) Thick vermilion border 12023989 IBIS 115 / 7739
61
 (HPO:0000212) Gingival overgrowth 25484423 IBIS 43 / 7739
62
 (HPO:0000230) Gingivitis 20155514 IBIS 31 / 7739
63
 (HPO:0002705) High, narrow palate 12023989 IBIS 308 / 7739
64
 (HPO:0000164) Abnormality of the teeth Frequent [IBIS] Very frequent [Orphanet] 13302174; 1190820; 25484423; 12023989 IBIS 291 / 7739
65
 (HPO:0006297) Hypoplasia of dental enamel 20155514 IBIS 64 / 7739
66
 (HPO:0006288) Advanced eruption of teeth Very frequent [Orphanet] 13302174; 1190820; 3415309; 20155514 IBIS 5 / 7739
67
 (HPO:0006337) Premature eruption of permanent teeth 13302174; 1190820; 3415309; 12023989 IBIS 2 / 7739
68
 (HPO:0000670) Carious teeth 13302174; 1190820; 20155514 IBIS 145 / 7739
69
 (HPO:0000678) Dental crowding 25484423; 12023989 IBIS 65 / 7739
70
 (HPO:0000221) Furrowed tongue 1190820; 25484423 IBIS 24 / 7739
71
 (HPO:0000154) Wide mouth 12023989 IBIS 137 / 7739
72
 (HPO:0000463) Anteverted nares 12023989 IBIS 305 / 7739
73
 (HPO:0000455) Broad nasal tip 12023989 IBIS 67 / 7739
74
 (HPO:0000445) Wide nose 25484423 IBIS 190 / 7739
75
 (HPO:0000400) Macrotia 3415309 IBIS 108 / 7739
76
 (HPO:0000391) Thickened helices 12023989 IBIS 8 / 7739
77
 (HPO:0000956) Acanthosis nigricans Frequent [IBIS] Very frequent [Orphanet] 2573522; 1190820; 3415309; 25484423; 12023989 IBIS 54 / 7739
78
 (HPO:0000953) Hyperpigmentation of the skin 13302174; 20155514 IBIS 75 / 7739
79
 (HPO:0000958) Dry skin Frequent [Orphanet] 1190820 IBIS 152 / 7739
80
 (HPO:0007495) Prematurely aged appearance Frequent [Orphanet] 13302174 IBIS 44 / 7739
81
 (HPO:0005328) Progeroid facial appearance 20155514 IBIS 13 / 7739
82
 (HPO:0100678) Premature skin wrinkling 13302174 IBIS 25 / 7739
83
 (HPO:0001072) Thickened skin Frequent [Orphanet] 13302174; 12023989 IBIS 87 / 7739
84
 (HPO:0000126) Hydronephrosis Occasional [Orphanet] 13302174 IBIS 119 / 7739
85
 (HPO:0000105) Enlarged kidneys 13302174; 20155514 IBIS 30 / 7739
86
 (HPO:0000103) Polyuria 13302174; 1190820; 25484423 IBIS 60 / 7739
87
 (HPO:0000072) Hydroureter Occasional [Orphanet] 13302174 IBIS 146 / 7739
88
 (HPO:0002919) Ketonuria 1190820; 3415309 IBIS 18 / 7739
89
 (HPO:0010313) Breast hypertrophy 20155514; 12023989 IBIS 6 / 7739
90
 (HPO:0000819) Diabetes mellitus Very frequent [Orphanet] 12023989 IBIS 131 / 7739
91
 (HPO:0005978) Type II diabetes mellitus 13302174 IBIS 68 / 7739
92
 (HPO:0001510) Growth delay Frequent [IBIS] 25484423; 20155514; 12023989 IBIS 295 / 7739
93
 (HPO:0008897) Postnatal growth retardation 25484423 IBIS 113 / 7739
94
 (HPO:0012689) Abnormal pineal melatonin secretion 3415309 IBIS 1 / 7739
95
 (HPO:3000033) Abnormality of nasopharyngeal adenoids 13302174 IBIS 4 / 7739
96
 (HPO:0012785) Flexion contracture of finger 12023989 IBIS 3 / 7739
97
 (HPO:0030348) Increased circulating androgen level 2573522 IBIS 8 / 7739
98
 (HPO:0012686) Increased pineal volume Frequent [IBIS] 13302174; 1190820; 25484423; 20155514 IBIS 1 / 7739
99
 (HPO:0040261) Increased size of nasopharyngeal adenoids 3415309 IBIS 4 / 7739

Associated genes:

INSR;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Rabson and Mendenhall (1956) described 3 sibs (2 girls, 1 boy) who initially presented with dental and skin abnormalities, abdominal distention, and phallic enlargement. The children demonstrated early dentition, a coarse, senile-appearing facies, and striking hirsutism. An 'adult ...
Molecular genetics OMIM In a patient with Rabson-Mendenhall syndrome described by Moncada et al. (1986), Kadowaki et al. (1990) identified compound heterozygosity for mutations in the INSR gene (147670.0012-147670.0003).