Hypothyroidism due to TSH receptor mutations

General Information (adopted from Orphanet):

Synonyms, Signs: TSH RESISTANCE
THYROID-STIMULATING HORMONE, RESISTANCE TO
THYROTROPIN RESISTANCE
HYPOTHYROIDISM DUE TO UNRESPONSIVENESS TO THYROTROPIN
HYPOTHYROIDISM, CONGENITAL, DUE TO TSH RESISTANCE
HYPOTHYROIDISM, NONAUTOIMMUNE
RTSH
CHNG1
Number of Symptoms 25
OrphanetNr: 90673
OMIM Id: 275200
ICD-10: E03.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Primary congenital hypothyroidism without thyroid developmental anomaly
 -Rare endocrine disease
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0000239) Large fontanelles Very frequent [Orphanet] 135 / 7739
2
(HPO:0000158) Macroglossia Very frequent [Orphanet] 119 / 7739
3
(HPO:0000271) Abnormality of the face Very frequent [Orphanet] 108 / 7739
4
(HPO:0002360) Sleep disturbance Very frequent [Orphanet] 113 / 7739
5
(HPO:0000821) Hypothyroidism Very frequent [Orphanet] 141 / 7739
6
(HPO:0005990) Thyroid hypoplasia 21 / 7739
7
(HPO:0002925) Thyroid-stimulating hormone excess 12 / 7739
8
(HPO:0000851) Congenital hypothyroidism 16 / 7739
9
(HPO:0001396) Cholestasis Very frequent [Orphanet] 136 / 7739
10
(HPO:0010318) Aplasia/Hypoplasia of the abdominal wall musculature Very frequent [Orphanet] 55 / 7739
11
(HPO:0002019) Constipation Very frequent [Orphanet] 194 / 7739
12
(HPO:0001537) Umbilical hernia Very frequent [Orphanet] 206 / 7739
13
(HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
14
(HPO:0000951) Abnormality of the skin Very frequent [Orphanet] 147 / 7739
15
(HPO:0001608) Abnormality of the voice Very frequent [Orphanet] 126 / 7739
16
(HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
17
(OMIM) Patients with hypothyroidism have hypoplastic thyroid gland 1 / 7739
18
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
19
(OMIM) Normal or mildly decreased serum levels of free thyroid hormones 1 / 7739
20
(OMIM) No goiter 1 / 7739
21
(HPO:0003593) Infantile onset 249 / 7739
22
(OMIM) Euthyroidism 1 / 7739
23
(OMIM) Hypothyroidism in subset of patients 1 / 7739
24
(OMIM) Absence of anti-thyroid antibodies 2 / 7739
25
(OMIM) Normal sized thyroid gland 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Resistance to thyroid-stimulating hormone (TSH; see 188540), a hallmark of congenital nongoitrous hypothyroidism, causes increased levels of plasma TSH and low levels of thyroid hormone. Only a subset of patients develop frank hypothyroidism; the remainder are euthyroid and ...
Diagnosis OMIM Takeshita et al. (1994) made the diagnosis of TSH unresponsiveness in 3 patients based on the following criteria: (1) congenital primary hypothyroidism with autosomal recessive inheritance; (2) a nongoitrous thyroid gland in a normal position with low thyroidal ...
Clinical Description OMIM Stanbury et al. (1968) described an 8-year-old boy with congenital hypothyroidism who was the offspring of parents related as first cousins once removed. He showed high serum levels of biologically active thyrotropin but no response to thyrotropin in ...
Molecular genetics OMIM In 3 sibs with normal serum thyroid hormone concentrations but high serum thyrotropin concentrations ('compensated hypothyroidism'), Sunthornthepvarakul et al. (1995) identified compound heterozygosity for 2 mutations in the TSHR gene (603372.0005; 603372.0006). Sunthornthepvarakul et al. (1995) concluded that ...