Laron syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: PITUITARY DWARFISM II
GROWTH HORMONE INSENSITIVITY SYNDROME
Laron-type dwarfism
growth hormone receptor deficiency
Primary growth hormone resistance
Primary growth hormone insensitivity
Primary GH resistance
GH receptor deficiency
Primary GH insensitivity
Short stature due to growth hormone resistance
Complete growth hormone insensitivity
Number of Symptoms 45
OrphanetNr: 633
OMIM Id: 262500
ICD-10: E34.3
UMLs: C0271568
MeSH: D046150
MedDRA:
Snomed: 38196001

Prevalence, inheritance and age of onset:

Prevalence: 0.2 of 100 000 [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Growth hormone insensitivity syndrome
 -Rare endocrine disease
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0012569) Delayed menarche 5 / 7739
2
 (HPO:0000054) Micropenis Frequent [Orphanet] 257 / 7739
3
 (HPO:0009804) Reduced number of teeth Very frequent [Orphanet] 137 / 7739
4
 (HPO:0000684) Delayed eruption of teeth Very frequent [Orphanet] 117 / 7739
5
 (HPO:0001999) Abnormal facial shape Very frequent [Orphanet] 169 / 7739
6
 (HPO:0000691) Microdontia Very frequent [Orphanet] 104 / 7739
7
 (HPO:0009924) Aplasia/Hypoplasia involving the nose Very frequent [Orphanet] 18 / 7739
8
 (HPO:0000929) Abnormality of the skull Occasional [Orphanet] 53 / 7739
9
 (HPO:0000277) Abnormality of the mandible Very frequent [Orphanet] 394 / 7739
10
 (HPO:0000348) High forehead Very frequent [Orphanet] 157 / 7739
11
 (HPO:0000457) Depressed nasal ridge Occasional [Orphanet] 85 / 7739
12
 (HPO:0009891) Underdeveloped supraorbital ridges Frequent [Orphanet] 36 / 7739
13
 (HPO:0000274) Small face 18 / 7739
14
 (HPO:0000592) Blue sclerae Occasional [Orphanet] Rare [HPO:probinson] 85 / 7739
15
 (HPO:0011442) Abnormality of central motor function Frequent [Orphanet] 76 / 7739
16
 (HPO:0000818) Abnormality of the endocrine system Very frequent [Orphanet] 26 / 7739
17
 (HPO:0008373) Puberty and gonadal disorders Frequent [Orphanet] 156 / 7739
18
 (HPO:0002750) Delayed skeletal maturation Very frequent [Orphanet] 250 / 7739
19
 (HPO:0009811) Abnormality of the elbow Frequent [Orphanet] 30 / 7739
20
 (HPO:0006494) Aplasia/Hypoplasia involving bones of the feet Frequent [Orphanet] 69 / 7739
21
 (HPO:0004279) Short palm Frequent [Orphanet] 323 / 7739
22
 (HPO:0003026) Short long bone 51 / 7739
23
 (HPO:0001367) Abnormal joint morphology 53 / 7739
24
 (HPO:0002758) Osteoarthritis Occasional [Orphanet] 78 / 7739
25
 (HPO:0003510) Severe short stature 90 / 7739
26
 (HPO:0004322) Short stature Very frequent [Orphanet] 1232 / 7739
27
 (HPO:0001956) Truncal obesity Very frequent [Orphanet] 39 / 7739
28
 (HPO:0007495) Prematurely aged appearance Occasional [Orphanet] 44 / 7739
29
 (HPO:0010720) Abnormal hair pattern Occasional [Orphanet] 14 / 7739
30
 (HPO:0003119) Abnormality of lipid metabolism Occasional [Orphanet] 60 / 7739
31
 (HPO:0001939) Abnormality of metabolism/homeostasis 328 / 7739
32
 (HPO:0004370) Abnormality of temperature regulation Occasional [Orphanet] 58 / 7739
33
 (HPO:0001943) Hypoglycemia Frequent [Orphanet] 131 / 7739
34
 (HPO:0001620) High pitched voice 32 / 7739
35
 (HPO:0001608) Abnormality of the voice Occasional [Orphanet] 126 / 7739
36
 (HPO:0003202) Skeletal muscle atrophy Frequent [Orphanet] 281 / 7739
37
 (OMIM) Failure to generate somatomedin (or insulinlike growth factor, IGF1) in response to growth hormone (139250). Normal or increased levels of GH. Growth hormone receptor (GHR) defect. Low IGF1 despite normal or increased levels of GH. 1 / 7739
38
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
39
 (HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
40
 (OMIM) Target resistance to the action of GH. 1 / 7739
41
 (OMIM) Delayed bone age. Markedly advanced osseous maturation for height and age. 1 / 7739
42
 (OMIM) Acrohypoplasia. Short limbs. 1 / 7739
43
 (OMIM) Occasionally blue sclerae. 1 / 7739
44
 (OMIM) Hip degeneration. Limited elbow extensibility. 1 / 7739
45
 (OMIM) Marked short stature. Clinical hyposomatotropism. Normal body proportions in childhood. Childlike body proportions in adults. Greater deviation of stature than head size. 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The ...
Diagnosis OMIM Laron syndrome is characterized by (1) clinical signs of GH deficiency (short stature, decreased growth velocity and delayed bone age) despite normal or increased plasma GH levels; (2) low IGF1 levels that are unresponsive to exogenous GH; and ...
Clinical Description OMIM Dysfunction of GHR is characterized by clinical hyposomatotropism manifest by short stature, delayed bone age, and occasionally blue sclerae and hip degeneration. Additional features include delayed bone maturation and the absence of bone dysplasias and chronic diseases. Laron ...
Molecular genetics OMIM See growth hormone receptor (600946) for a description of mutations in the GHR gene in Laron syndrome.

Berg et al. (1993) reported that 10 GHR mutations had been reported in Laron syndrome to that time; one ...
Population genetics OMIM The GHR defects known to cause Laron syndrome are as a rule heterogeneous and include gene deletion, recurring CpG dinucleotide substitutions, and other point mutations (Phillips, 1992). Interestingly, in an inbred Ecuadorian population of Spanish extraction, despite homozygosity ...