Leprechaunism

General Information (adopted from Orphanet):

Synonyms, Signs: Leprechaunism insulin receptor, defect in, included
Donohue syndrome
Number of Symptoms 148
OrphanetNr: 508
OMIM Id: 246200
ICD-10: E34.8
UMLs:
MeSH:
MedDRA:
Snomed: 111307005

Prevalence, inheritance and age of onset:

Prevalence: <= 0.03 of 100 000 - PMID: 9128805 [IBIS]
Inheritance: Autosomal recessive
- PMID: 12023989 [IBIS]
Age of onset: Antenatal
Neonatal
- PMID: 12023989 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Genetic progeroid syndrome
 -Rare genetic disease
Hypertrichosis
 -Rare genetic disease
 -Rare skin disease
Insulin-resistance syndrome
 -Rare endocrine disease
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare developmental defect during embryogenesis
Progeroid syndrome
 -Rare developmental defect during embryogenesis

Comment:

Leprechaunism is a monogenic form of diabetes caused by mutations in INSR (PMID:21127150).

Symptom Information: Sort by abundance 

1
 (HPO:0001522) Death in infancy Very frequent [IBIS] 12023989; 13212592; 293690; 9128805; 26871809 IBIS 275 / 7739
2
 (HPO:0001510) Growth delay Very frequent [IBIS] Very frequent [Orphanet] 12023989 IBIS 295 / 7739
3
 (HPO:0005978) Type II diabetes mellitus Very frequent [IBIS] Very frequent [Orphanet] 9128805; 6999010 IBIS 68 / 7739
4
 (HPO:0000956) Acanthosis nigricans Frequent [IBIS] 12023989; 9128805; 277948 IBIS 54 / 7739
5
 (HPO:0001999) Abnormal facial shape Very frequent [IBIS] Very frequent [Orphanet] 12023989; 13212592; 14065999; 9128805; 26871809; 6999010; 3309859 IBIS 169 / 7739
6
 (HPO:0000811) Abnormal external genitalia Frequent [IBIS] 12023989 IBIS 6 / 7739
7
 (HPO:0000818) Abnormality of the endocrine system Very frequent [IBIS] 9128805 IBIS 26 / 7739
8
 (HPO:0004510) Pancreatic islet-cell hyperplasia Frequent [IBIS] 14065999; 293690; 9128805; 3309859 IBIS 9 / 7739
9
 (HPO:0000998) Hypertrichosis Frequent [IBIS] Frequent [Orphanet] 13212592; 14065999; 26871809; 277948; 3309859 IBIS 52 / 7739
10
 (HPO:0001007) Hirsutism Frequent [IBIS] Frequent [Orphanet] typical [HPO] 12023989; 293690 IBIS 91 / 7739
11
 (HPO:0001511) Intrauterine growth retardation Very frequent [IBIS] Very frequent [Orphanet] 12023989; 9128805; 26871809 IBIS 358 / 7739
12
 (HPO:0003202) Skeletal muscle atrophy Frequent [IBIS] Very frequent [Orphanet] 13212592; 3309859 IBIS 281 / 7739
13
 (HPO:0000855) Insulin resistance Frequent [IBIS] 293690; 9128805; 3309859 IBIS 32 / 7739
14
 (HPO:0000842) Hyperinsulinemia Very frequent [IBIS] Very frequent [Orphanet] 12023989; 293690; 26871809; 6999010; 3309859 IBIS 39 / 7739
15
 (HPO:0011014) Abnormal glucose homeostasis Frequent [IBIS] 12023989; 9128805 IBIS 5 / 7739
16
 (HPO:0001518) Small for gestational age Frequent [IBIS] 12023989; 13212592; 293690; 26871809; 6999010; 277948 IBIS 107 / 7739
17
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 12023989; 293690; 26871809; 6999010 IBIS 492 / 7739
18
 (HPO:0001508) Failure to thrive Frequent [IBIS] Very frequent [Orphanet] 12023989; 13212592; 14065999; 293690 IBIS 454 / 7739
19
 (HPO:0007485) Absence of subcutaneous fat Frequent [IBIS] 12023989; 13212592; 14065999; 293690; 277948; 3309859 IBIS 6 / 7739
20
 (HPO:0100578) Lipoatrophy Frequent [IBIS] Frequent [Orphanet] 9128805; 26871809 IBIS 30 / 7739
21
 (HPO:0003270) Abdominal distention 12023989; 13212592; 26871809; 277948 IBIS 46 / 7739
22
 (HPO:0001538) Protuberant abdomen 12023989 IBIS 36 / 7739
23
 (HPO:0008872) Feeding difficulties in infancy Frequent [Orphanet] 14065999 IBIS 153 / 7739
24
 (HPO:0003282) Low alkaline phosphatase 14065999 IBIS 7 / 7739
25
 (HPO:0000316) Hypertelorism Very frequent [Orphanet] 9128805 IBIS 644 / 7739
26
 (HPO:0001090) Large eyes 9128805 IBIS 20 / 7739
27
 (HPO:0002097) Emphysema 13212592 IBIS 40 / 7739
28
 (HPO:0006515) Interstitial pneumonitis 13212592 IBIS 13 / 7739
29
 (HPO:0011950) Bronchiolitis 13212592 IBIS 8 / 7739
30
 (HPO:0002090) Pneumonia 293690 IBIS 59 / 7739
31
 (HPO:0006532) Recurrent pneumonia 14065999 IBIS 48 / 7739
32
 (HPO:0009064) Generalized lipodystrophy 9128805 IBIS 17 / 7739
33
 (HPO:0004322) Short stature Very frequent [Orphanet] 6999010 IBIS 1232 / 7739
34
 (HPO:0003510) Severe short stature Very frequent [Orphanet] 26871809 IBIS 90 / 7739
35
 (HPO:0003074) Hyperglycemia 12023989; 26871809 IBIS 37 / 7739
36
 (HPO:0011998) Postprandial hyperglycemia 12023989 IBIS 5 / 7739
37
 (HPO:0001943) Hypoglycemia Very frequent [Orphanet] 12023989 IBIS 131 / 7739
38
 (HPO:0001998) Neonatal hypoglycemia 26871809 IBIS 22 / 7739
39
 (HPO:0003355) Aminoaciduria 14065999; 293690 IBIS 65 / 7739
40
 (HPO:0003231) Hypertyrosinemia 293690 IBIS 8 / 7739
41
 (HPO:0001640) Cardiomegaly 293690 IBIS 81 / 7739
42
 (HPO:0001631) Atria septal defect 12023989 IBIS 274 / 7739
43
 (HPO:0001712) Left ventricular hypertrophy 12023989 IBIS 76 / 7739
44
 (HPO:0001639) Hypertrophic cardiomyopathy 12023989; 3309859 IBIS 137 / 7739
45
 (HPO:0001723) Restrictive cardiomyopathy 12023989 IBIS 22 / 7739
46
 (HPO:0001643) Patent ductus arteriosus 293690 IBIS 228 / 7739
47
 (HPO:0001662) Bradycardia 12023989; 26871809 IBIS 41 / 7739
48
 (HPO:0001649) Tachycardia 293690; 26871809 IBIS 53 / 7739
49
 (HPO:0001695) Cardiac arrest 26871809 IBIS 87 / 7739
50
 (HPO:0001635) Congestive heart failure 12023989 IBIS 232 / 7739
51
 (HPO:0001699) Sudden death 293690 IBIS 34 / 7739
52
 (HPO:0003162) Fasting hypoglycemia 12023989 IBIS 8 / 7739
53
 (HPO:0001903) Anemia 26871809 IBIS 289 / 7739
54
 (HPO:0100838) Recurrent cutaneous abscess formation 13212592 IBIS 15 / 7739
55
 (HPO:0100806) Sepsis 26871809 IBIS 48 / 7739
56
 (HPO:0002900) Hypokalemia 26871809 IBIS 45 / 7739
57
 (MedDRA:10072081) Bandaemia 12023989 IBIS 1 / 7739
58
 (HPO:0001974) Leukocytosis 12023989 IBIS 33 / 7739
59
 (HPO:0001882) Leukopenia 26871809 IBIS 51 / 7739
60
 (HPO:0003146) Hypocholesterolemia 14065999; 26871809 IBIS 9 / 7739
61
 (HPO:0012153) Hypotriglyceridemia 26871809 IBIS 4 / 7739
62
 (HPO:0003199) Decreased muscle mass 293690 IBIS 27 / 7739
63
 (HPO:0003560) Muscular dystrophy Very frequent [Orphanet] 14065999 IBIS 88 / 7739
64
 (HPO:0001336) Myoclonus 14065999 IBIS 115 / 7739
65
 (HPO:0001257) Spasticity 14065999 IBIS 251 / 7739
66
 (HPO:0001959) Polydipsia 277948 IBIS 43 / 7739
67
 (HPO:0008846) Severe intrauterine growth retardation 26871809; 3309859 IBIS 5 / 7739
68
 (HPO:0001562) Oligohydramnios 12023989 IBIS 75 / 7739
69
 (HPO:0001833) Long foot 14065999 IBIS 33 / 7739
70
 (HPO:0001176) Large hands 14065999 IBIS 43 / 7739
71
 (HPO:0010537) Wide cranial sutures 13212592 IBIS 21 / 7739
72
 (HPO:0011328) Abnormality of fontanelles 14065999 IBIS 1 / 7739
73
 (HPO:0000252) Microcephaly Occasional [Orphanet] 14065999 IBIS 832 / 7739
74
 (HPO:0002750) Delayed skeletal maturation Frequent [Orphanet] 14065999 IBIS 250 / 7739
75
 (HPO:0003799) Marked delay in bone age 8105179 IBIS 5 / 7739
76
 (HPO:0011359) Dry hair 13212592 IBIS 16 / 7739
77
 (HPO:0002230) Generalized hirsutism Frequent [Orphanet] typical [HPO] 12023989; 277948 IBIS 32 / 7739
78
 (HPO:0009937) Facial hirsutism 14065999; 9128805 IBIS 4 / 7739
79
 (HPO:0011335) Frontal hirsutism 14065999 IBIS 4 / 7739
80
 (HPO:0002164) Nail dysplasia 277948 IBIS 82 / 7739
81
 (HPO:0000975) Hyperhidrosis 6999010 IBIS 64 / 7739
82
 (HPO:0001945) Fever 26871809 IBIS 218 / 7739
83
 (HPO:0002570) Steatorrhea 14065999 IBIS 31 / 7739
84
 (HPO:0001396) Cholestasis Frequent [Orphanet] 12023989 IBIS 136 / 7739
85
 (HPO:0000952) Jaundice Frequent [Orphanet] 26871809 IBIS 105 / 7739
86
 (HPO:0002240) Hepatomegaly 14065999 IBIS 467 / 7739
87
 (HPO:0012094) Abnormal pancreas size 14065999 IBIS 5 / 7739
88
 (HPO:0006476) Abnormality of the pancreatic islet cells 13212592 IBIS 1 / 7739
89
 (HPO:0006270) Hypoplastic spleen 14065999 IBIS 4 / 7739
90
 (HPO:0001537) Umbilical hernia Frequent [Orphanet] 277948 IBIS 206 / 7739
91
 (HPO:0000023) Inguinal hernia Frequent [Orphanet] 12023989; 277948 IBIS 181 / 7739
92
 (HPO:0000478) Abnormality of the eye 13212592 IBIS 126 / 7739
93
 (HPO:0008665) Clitoral hypertrophy 13212592; 277948; 277948; 3309859 IBIS 10 / 7739
94
 (HPO:0000057) Clitoromegaly 12023989 IBIS 30 / 7739
95
 (HPO:0000065) Labial hypertrophy 13212592 IBIS 4 / 7739
96
 (HPO:0003247) Overgrowth of external genitalia 26871809 IBIS 3 / 7739
97
 (HPO:0100879) Enlarged ovaries 13212592 IBIS 1 / 7739
98
 (HPO:0008675) Enlarged polycystic ovaries 12023989 IBIS 14 / 7739
99
 (HPO:0000138) Ovarian cyst 13212592; 3309859 IBIS 25 / 7739
100
 (HPO:0000147) Polycystic ovaries 12023989 IBIS 18 / 7739
101
 (HPO:0100878) Enlarged uterus 13212592 IBIS 1 / 7739
102
 (HPO:0000034) Hydrocele testis 26871809 IBIS 18 / 7739
103
 (HPO:0000280) Coarse facial features 277948 IBIS 189 / 7739
104
 (HPO:0004428) Elfin facies 13212592; 14065999; 26871809 IBIS 5 / 7739
105
 (HPO:0000274) Small face 12023989 IBIS 18 / 7739
106
 (HPO:0012471) Thick vermilion border 12023989; 13212592; 9128805; 277948 IBIS 115 / 7739
107
 (HPO:0000212) Gingival overgrowth 12023989; 277948 IBIS 43 / 7739
108
 (HPO:0002705) High, narrow palate Very frequent [Orphanet] 3309859 IBIS 308 / 7739
109
 (HPO:0005326) Hypoplastic philtrum 3309859 IBIS 4 / 7739
110
 (HPO:0000219) Thin upper lip vermilion 3309859 IBIS 112 / 7739
111
 (HPO:0000454) Flared nostrils 12023989; 13212592 IBIS 11 / 7739
112
 (HPO:0000463) Anteverted nares 3309859 IBIS 305 / 7739
113
 (HPO:0000455) Broad nasal tip 13212592 IBIS 67 / 7739
114
 (HPO:0005280) Depressed nasal bridge Frequent [Orphanet] 12023989; 3309859 IBIS 381 / 7739
115
 (HPO:0000606) Abnormality of the periorbital region 3309859 IBIS 96 / 7739
116
 (HPO:0000845) Growth hormone excess 8105179 IBIS 18 / 7739
117
 (HPO:0000778) Hypoplasia of the thymus 14065999 IBIS 13 / 7739
118
 (HPO:0004405) Prominent nipples 13212592; 277948; 3309859 IBIS 2 / 7739
119
 (HPO:0008559) Hypoplastic superior helix 3309859 IBIS 6 / 7739
120
 (HPO:0000400) Macrotia Very frequent [Orphanet] 12023989; 13212592; 14065999; 9128805; 26871809 IBIS 108 / 7739
121
 (HPO:0000369) Low-set ears Very frequent [Orphanet] hallmark [HPO] 13212592; 14065999; 293690; 9128805; 26871809 IBIS 372 / 7739
122
 (HPO:0000368) Low-set, posteriorly rotated ears Very frequent [Orphanet] 3309859 IBIS 38 / 7739
123
 (HPO:0000358) Posteriorly rotated ears Very frequent [Orphanet] hallmark [HPO] 3309859 IBIS 163 / 7739
124
 (HPO:0002104) Apnea 12023989 IBIS 106 / 7739
125
 (HPO:0000951) Abnormality of the skin 26871809 IBIS 147 / 7739
126
 (HPO:0001034) Hypermelanotic macule 277948 IBIS 22 / 7739
127
 (HPO:0000973) Cutis laxa 13212592 IBIS 43 / 7739
128
 (HPO:0000958) Dry skin 13212592 IBIS 152 / 7739
129
 (HPO:0000980) Pallor 26871809 IBIS 52 / 7739
130
 (HPO:0000961) Cyanosis 13212592; 14065999 IBIS 60 / 7739
131
 (HPO:0005328) Progeroid facial appearance 9128805 IBIS 13 / 7739
132
 (HPO:0100678) Premature skin wrinkling 12023989 IBIS 25 / 7739
133
 (HPO:0001072) Thickened skin 277948 IBIS 87 / 7739
134
 (HPO:0005990) Thyroid hypoplasia 14065999 IBIS 21 / 7739
135
 (HPO:0000126) Hydronephrosis 26871809 IBIS 119 / 7739
136
 (HPO:0000105) Enlarged kidneys 13212592; 14065999 IBIS 30 / 7739
137
 (HPO:0000103) Polyuria 277948 IBIS 60 / 7739
138
 (HPO:0000093) Proteinuria 293690 IBIS 169 / 7739
139
 (HPO:0001905) Congenital thrombocytopenia 26871809 IBIS 4 / 7739
140
 (HPO:0010313) Breast hypertrophy Frequent [Orphanet] 12023989; 13212592 IBIS 6 / 7739
141
 (HPO:0008897) Postnatal growth retardation Frequent [IBIS] 9128805; 26871809 IBIS 113 / 7739
142
 (HPO:0002904) Hyperbilirubinemia 12023989; 293690 IBIS 32 / 7739
143
 (HPO:0030148) Heart murmur 12023989; 13212592; 3309859 IBIS 29 / 7739
144
 (HPO:0012882) Hyperplastic labia majora 12023989; 277948; 277948 IBIS 2 / 7739
145
 (HPO:0001339) Lissencephaly 14065999 IBIS 30 / 7739
146
 (MedDRA:10022478) Insulin C-peptide increased 26871809 IBIS 2 / 7739
147
 (MedDRA:10073260) Ovarian granulosa cell tumour 12023989 IBIS 1 / 7739
148
 (MedDRA:10048709) Urosepsis 26871809 IBIS 3 / 7739

Associated genes:

INSR;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Among the children of second cousins once removed, Donohue and Uchida (1954) observed 2 sisters with the following features: apparent cessation of growth at about the seventh month of gestation, peculiar facies creating a gnomelike appearance and leading ...
Molecular genetics OMIM Psiachou et al. (1993) reported a female infant with leprechaunism who was homozygous by descent for a null allele of the insulin receptor gene. The mutation involved replacement of a 13-bp sequence in exon 13 by an unrelated ...