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Isolated growth hormone deficiency, type 4(IGHD4; IGHD1B, FORMERLY)

MedGen UID:
1648300
•Concept ID:
C4722273
•
Disease or Syndrome
Synonyms: DWARFISM OF SINDH; ISOLATED GROWTH HORMONE DEFICIENCY, TYPE IV
 
Gene (location): GHRHR (7p14.3)
 
Monarch Initiative: MONDO:0032567
OMIM®: 618157

Definition

Isolated growth hormone deficiency type IV (IGHD4) is an autosomal recessive disorder characterized by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I (IGF1; 147440) and IGF-binding protein-3 (IGFBP3; 146732) concentrations, and a good response to growth hormone treatment (summary by Alatzoglou et al., 2014). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400. [from OMIM]

Clinical features

From HPO
Severe short stature
MedGen UID:
3931
•Concept ID:
C0013336
•
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
See: Feature record | Search on this feature
Anterior pituitary hypoplasia
MedGen UID:
347950
•Concept ID:
C1859775
•
Congenital Abnormality
Underdevelopment of the anterior pituitary gland.
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 serum insulin-like growth factor 1
MedGen UID:
892792
•Concept ID:
C4072897
•
Finding
A reduced level of insulin-like growth factor 1 (IGF1) in the blood circulation.
See: Feature record | Search on this feature
Impaired growth-hormone response to insulin stimulation test
MedGen UID:
1374054
•Concept ID:
C4476958
•
Finding
Failure of growth hormone levels to respond adequately (by increasing) to the insulin tolerance test (ITT).
See: Feature record | Search on this feature
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
•Concept ID:
C5539399
•
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.
Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, Hoffman AR
Endocr Pract 2019 Nov;25(11):1191-1232. doi: 10.4158/GL-2019-0405. PMID: 31760824
Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome.
Kamel A, Norgren S, Lindgren AC, Luthman H, Arner P, Marcus C
Eur J Endocrinol 1998 May;138(5):510-6. doi: 10.1530/eje.0.1380510. PMID: 9625361
Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone.
Zachmann M, Fernandez F, Tassinari D, Thakker R, Prader A
Eur J Pediatr 1980 May;133(3):277-82. doi: 10.1007/BF00496089. PMID: 7389741

Recent clinical studies

Etiology

Prevalence of brain MRI findings in children with nonacquired growth hormone deficiency: a systematic review and meta-analysis.
Hwang J, Jo SW, Kwon EB, Lee SA, Chang SK
Neuroradiology 2021 Jul;63(7):1121-1133. Epub 2021 Feb 20 doi: 10.1007/s00234-021-02665-3. PMID: 33611620
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.
Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, Hoffman AR
Endocr Pract 2019 Nov;25(11):1191-1232. doi: 10.4158/GL-2019-0405. PMID: 31760824
SHORT STATURE: WHA T IS THE CAUSE IN OUR POPULATION.
Ullah F, Ghaffar T, Afridi AK, Ali A, Aamir Au
J Ayub Med Coll Abbottabad 2016 Jan-Mar;28(1):135-40. PMID: 27323579
Growth hormone (GH-1) gene deletions in children with isolated growth hormone deficiency (IGHD).
Desai MP, Mithbawkar SM, Upadhye PS, Shalia KK
Indian J Pediatr 2012 Jul;79(7):875-83. Epub 2011 Oct 21 doi: 10.1007/s12098-011-0588-5. PMID: 22016154
Isolated growth hormone deficiency.
Hernández LM, Lee PD, Camacho-Hübner C
Pituitary 2007;10(4):351-7. doi: 10.1007/s11102-007-0073-3. PMID: 17965963

Diagnosis

Diagnosis of Growth Hormone Deficiency in Children: The Efficacy of Glucagon versus Clonidine Stimulation Test.
Yackobovitch-Gavan M, Lazar L, Diamant R, Phillip M, Oron T
Horm Res Paediatr 2020;93(7-8):470-476. Epub 2021 Feb 10 doi: 10.1159/000513393. PMID: 33567442
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.
Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, Hoffman AR
Endocr Pract 2019 Nov;25(11):1191-1232. doi: 10.4158/GL-2019-0405. PMID: 31760824
MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature.
Wit JM, Oostdijk W, Losekoot M, van Duyvenvoorde HA, Ruivenkamp CA, Kant SG
Eur J Endocrinol 2016 Apr;174(4):R145-73. Epub 2015 Nov 17 doi: 10.1530/EJE-15-0937. PMID: 26578640
Molecular aspects of thyroid hormone actions.
Cheng SY, Leonard JL, Davis PJ
Endocr Rev 2010 Apr;31(2):139-70. Epub 2010 Jan 5 doi: 10.1210/er.2009-0007. PMID: 20051527Free PMC Article
Isolated growth hormone deficiency.
Hernández LM, Lee PD, Camacho-Hübner C
Pituitary 2007;10(4):351-7. doi: 10.1007/s11102-007-0073-3. PMID: 17965963

Therapy

The response to growth hormone treatment in a child with short stature, growth hormone deficiency and autosomal dominant cutis laxa type 3 - case report.
Iancu ME, Albu AI, Albu DN
J Pediatr Endocrinol Metab 2022 Sep 27;35(9):1211-1214. Epub 2022 Jul 1 doi: 10.1515/jpem-2022-0054. PMID: 35770839
Isolated Growth Hormone Deficiency Type 2 due to a novel GH1 Mutation: A Case Report.
Kautsar A, Wit JM, Pulungan A
J Clin Res Pediatr Endocrinol 2019 Nov 22;11(4):426-431. Epub 2019 Jan 25 doi: 10.4274/jcrpe.galenos.2019.2018.0305. PMID: 30678423Free PMC Article
Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential.
Yada T, Dezaki K, Sone H, Koizumi M, Damdindorj B, Nakata M, Kakei M
Curr Diabetes Rev 2008 Feb;4(1):18-23. doi: 10.2174/157339908783502352. PMID: 18220691
Catch-up growth in autosomal dominant isolated growth hormone deficiency (IGHD type II).
Binder G, Iliev DI, Mullis PE, Ranke MB
Growth Horm IGF Res 2007 Jun;17(3):242-8. Epub 2007 Mar 13 doi: 10.1016/j.ghir.2007.01.014. PMID: 17360215
Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone.
Zachmann M, Fernandez F, Tassinari D, Thakker R, Prader A
Eur J Pediatr 1980 May;133(3):277-82. doi: 10.1007/BF00496089. PMID: 7389741

Prognosis

Different Growth Responses to Recombinant Human Growth Hormone in Three Siblings with Isolated Growth Hormone Deficiency Type 1A due to a 6.7Kb Deletion in the GH1 Gene.
Ghosh S, Chakraborty PP, Bankura B, Maiti A, Biswas R, Das M
J Clin Res Pediatr Endocrinol 2021 Nov 25;13(4):456-460. Epub 2020 Sep 17 doi: 10.4274/jcrpe.galenos.2020.2020.0005. PMID: 32936763Free PMC Article
Identification of a novel immune prognostic model in gastric cancer.
Li Y, He X, Fan L, Zhang X, Xu Y, Xu X
Clin Transl Oncol 2021 Apr;23(4):846-855. Epub 2020 Aug 28 doi: 10.1007/s12094-020-02478-5. PMID: 32857339
Diagnosis of Growth Hormone Deficiency in Children: The Efficacy of Glucagon versus Clonidine Stimulation Test.
Yackobovitch-Gavan M, Lazar L, Diamant R, Phillip M, Oron T
Horm Res Paediatr 2020;93(7-8):470-476. Epub 2021 Feb 10 doi: 10.1159/000513393. PMID: 33567442
Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study.
Mullis PE, Robinson IC, Salemi S, Eblé A, Besson A, Vuissoz JM, Deladoey J, Simon D, Czernichow P, Binder G
J Clin Endocrinol Metab 2005 Apr;90(4):2089-96. Epub 2005 Jan 25 doi: 10.1210/jc.2004-1280. PMID: 15671105
Transitory growth hormone deficiency successfully treated with human growth hormone.
Trygstad O
Acta Endocrinol (Copenh) 1977 Jan;84(1):11-22. doi: 10.1530/acta.0.0840011. PMID: 576178

Clinical prediction guides

Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report.
Yang X, Yuan M, Li Z, Ying Y, Hou L, Luo X
BMC Med Genomics 2021 Sep 2;14(1):210. doi: 10.1186/s12920-021-01057-z. PMID: 34470639Free PMC Article
Diagnosis of Growth Hormone Deficiency in Children: The Efficacy of Glucagon versus Clonidine Stimulation Test.
Yackobovitch-Gavan M, Lazar L, Diamant R, Phillip M, Oron T
Horm Res Paediatr 2020;93(7-8):470-476. Epub 2021 Feb 10 doi: 10.1159/000513393. PMID: 33567442
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.
Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, Hoffman AR
Endocr Pract 2019 Nov;25(11):1191-1232. doi: 10.4158/GL-2019-0405. PMID: 31760824
MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation.
Aguiar-Oliveira MH, Souza AHO, Oliveira CRP, Campos VC, Oliveira-Neto LA, Salvatori R
Eur J Endocrinol 2017 Aug;177(2):R85-R97. Epub 2017 Apr 20 doi: 10.1530/EJE-16-1047. PMID: 28428227
The in vivo roles of müllerian-inhibiting substance.
Behringer RR
Curr Top Dev Biol 1994;29:171-87. doi: 10.1016/s0070-2153(08)60550-5. PMID: 7828438

Recent systematic reviews

Can GH Therapy Worsen a Clinically Silent Chiari Malformation? A Case Report and Systematic Literature Review.
Candela E, La Corte E, Zucchini S, Lefosse M, Toni F, Zucchelli M
Horm Res Paediatr 2023;96(4):349-355. Epub 2022 Aug 24 doi: 10.1159/000526617. PMID: 36001954
Prevalence of brain MRI findings in children with nonacquired growth hormone deficiency: a systematic review and meta-analysis.
Hwang J, Jo SW, Kwon EB, Lee SA, Chang SK
Neuroradiology 2021 Jul;63(7):1121-1133. Epub 2021 Feb 20 doi: 10.1007/s00234-021-02665-3. PMID: 33611620

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