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Hypothyroidism, congenital, nongoitrous, 7

MedGen UID:
1372458
•Concept ID:
C4511136
•
Disease or Syndrome
Synonym: Resistance to thyrotropin-releasing hormone syndrome
SNOMED CT: Resistance to thyrotropin-releasing hormone syndrome (725462002); TRH (thyrotropin-releasing hormone) resistance syndrome (725462002); Congenital central hypothyroidism due to thyrotropin-releasing hormone receptor deficiency (725462002)
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).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): TRHR (8q23.1)
 
Monarch Initiative: MONDO:0032819
OMIM®: 618573
Orphanet: ORPHA99832

Definition

Nongoitrous congenital hypothyroidism-7 (CHNG7) is characterized by normal-to-low T4 and normal-to-high thyrotropin (TSH; see 188540) levels, with reduced or absent pituitary responsiveness to thyrotropin-releasing hormone (TRH; 613879). Patients may exhibit short stature, growth retardation, and delayed bone age, as well as lethargy or fatigue (Collu et al., 1997; Bonomi et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of congenital nongoitrous hypothyroidism, see 275200. [from OMIM]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
•Concept ID:
C0015672
•
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
See: Feature record | Search on this feature
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).
See: Feature record | Search on this feature
Growth delay
MedGen UID:
99124
•Concept ID:
C0456070
•
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
See: Feature record | Search on this feature
Lethargy
MedGen UID:
7310
•Concept ID:
C0023380
•
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
See: Feature record | Search on this feature
Delayed skeletal maturation
MedGen UID:
108148
•Concept ID:
C0541764
•
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
See: Feature record | Search on this feature
Decreased circulating T4 concentration
MedGen UID:
1611997
•Concept ID:
C4531078
•
Finding
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).
See: Feature record | Search on this feature
Reduced TSH response to thyrotrophin-releasing hormone stimulation test
MedGen UID:
1759429
•Concept ID:
C5421596
•
Finding
A lower than normal TSH response to thyrotrophin-releasing hormone stimulation test.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypothyroidism, congenital, nongoitrous, 7

Recent clinical studies

Etiology

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309
Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas.
Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P
J Clin Endocrinol Metab 1989 Aug;69(2):359-63. doi: 10.1210/jcem-69-2-359. PMID: 2753978

Diagnosis

Impaired Sensitivity to Thyroid Hormones Is Associated With Decreased Vitamin D Levels in the Euthyroid Population.
Li Y, Sun J, Jiao Y, Li N, Zhao W
J Clin Endocrinol Metab 2024 Feb 20;109(3):691-700. doi: 10.1210/clinem/dgad607. PMID: 37831130
Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.
Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
Congenital nongoitrous hypothyroidism.
Hahn HB
Postgrad Med 1975 Jun;57(7):71-4. doi: 10.1080/00325481.1975.11714074. PMID: 48245

Therapy

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.
Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309
Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas.
Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P
J Clin Endocrinol Metab 1989 Aug;69(2):359-63. doi: 10.1210/jcem-69-2-359. PMID: 2753978
Congenital nongoitrous hypothyroidism.
Hahn HB
Postgrad Med 1975 Jun;57(7):71-4. doi: 10.1080/00325481.1975.11714074. PMID: 48245

Prognosis

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.
Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276

Clinical prediction guides

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.
Martín M, Bernal Barquero CE, Geysels RC, Papendieck P, Peyret V, Masini-Repiso AM, Chiesa AE, Nicola JP
Thyroid 2019 Jul;29(7):1023-1026. Epub 2019 Jul 2 doi: 10.1089/thy.2019.0046. PMID: 31115276
The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309

Supplemental Content

Table of contents

    Clinical resources

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

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