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Male hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome

MedGen UID:
334557
•Concept ID:
C1843994
•
Disease or Syndrome
Synonym: Hypogonadism, Male, With Mental Retardation And Skeletal Anomalies
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
•Concept ID:
CN307042
•
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
See: This record
Unknown inheritance (Orphanet)
 
Monarch Initiative: MONDO:0010617
OMIM®: 307500
Orphanet: ORPHA2234

Definition

This syndrome is characterized by hypergonadotropic hypogonadism, intellectual deficit, congenital skeletal anomalies involving the cervical spine and superior ribs, and diabetes mellitus. [from ORDO]

Clinical features

From HPO
Intellectual disability
MedGen UID:
811461
•Concept ID:
C3714756
•
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
See: Feature record | Search on this feature
Skeletal dysplasia
MedGen UID:
98053
•Concept ID:
C0410528
•
Disease or Syndrome
A general term describing features characterized by abnormal development of bones and connective tissues.
See: Feature record | Search on this feature
Abnormality of the cervical spine
MedGen UID:
338935
•Concept ID:
C1852464
•
Anatomical Abnormality
Any abnormality of the cervical vertebral column.
See: Feature record | Search on this feature
Superior rib anomalies
MedGen UID:
870675
•Concept ID:
C4025129
•
Anatomical Abnormality
See: Feature record | Search on this feature
Hyperglycemia
MedGen UID:
5689
•Concept ID:
C0020456
•
Disease or Syndrome
An increased concentration of glucose in the blood.
See: Feature record | Search on this feature
Glucose intolerance
MedGen UID:
75760
•Concept ID:
C0271650
•
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
See: Feature record | Search on this feature
Male hypogonadism
MedGen UID:
57480
•Concept ID:
C0151721
•
Disease or Syndrome
Familial male hypogonadism is a highly heterogeneous category from which some disorders such as Reifenstein syndrome (312300), Kallmann syndrome (see 308700), isolated gonadotropin deficiency, and some other entities can be separated. The presence of an autosomal recessive form is suggested by the occurrence of parental consanguinity (Nowakowski and Lenz, 1961).
See: Feature record | Search on this feature
Hypergonadotropic hypogonadism
MedGen UID:
184926
•Concept ID:
C0948896
•
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMale hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome

Professional guidelines

PubMed

The genetic basis of female reproductive disorders: etiology and clinical testing.
Layman LC
Mol Cell Endocrinol 2013 May 6;370(1-2):138-48. Epub 2013 Mar 14 doi: 10.1016/j.mce.2013.02.016. PMID: 23499866Free PMC Article

Recent clinical studies

Etiology

Hypergonadotropic hypogonadism and chromosomal aberrations: clinical heterogeneity and implications on the health of elderly men, case series.
Elhadd T, Majzoub A, Wilson C, McCreight L, Mohamed MS, Green FC, Collier AJ
BMC Endocr Disord 2023 May 17;23(1):110. doi: 10.1186/s12902-023-01359-6. PMID: 37198592Free PMC Article
Pattern of Male Hypogonadism and Outcome of Treatment in South Rajasthan.
Sharma KR, Sharma H, Vishnoi J, Sharma RK, Goel S
J Assoc Physicians India 2022 Apr;70(4):11-12. PMID: 35443335
Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.
Salzano A, D'Assante R, Heaney LM, Monaco F, Rengo G, Valente P, Pasquali D, Bossone E, Gianfrilli D, Lenzi A, Cittadini A, Marra AM, Napoli R
Endocrine 2018 Aug;61(2):194-203. Epub 2018 Mar 23 doi: 10.1007/s12020-018-1584-6. PMID: 29572708
Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders.
Calogero AE, Giagulli VA, Mongioì LM, Triggiani V, Radicioni AF, Jannini EA, Pasquali D; Klinefelter ItaliaN Group (KING)
J Endocrinol Invest 2017 Jul;40(7):705-712. Epub 2017 Mar 3 doi: 10.1007/s40618-017-0619-9. PMID: 28258556
Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism.
Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A; Klinefelter ItaliaN Group (KING)
J Endocrinol Invest 2017 Feb;40(2):123-134. Epub 2016 Sep 19 doi: 10.1007/s40618-016-0541-6. PMID: 27644703Free PMC Article

Diagnosis

Hypergonadotropic hypogonadism and chromosomal aberrations: clinical heterogeneity and implications on the health of elderly men, case series.
Elhadd T, Majzoub A, Wilson C, McCreight L, Mohamed MS, Green FC, Collier AJ
BMC Endocr Disord 2023 May 17;23(1):110. doi: 10.1186/s12902-023-01359-6. PMID: 37198592Free PMC Article
Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.
Serbis A, Rallis D, Giapros V, Galli-Tsinopoulou A, Siomou E
Int J Mol Sci 2023 Feb 12;24(4) doi: 10.3390/ijms24043690. PMID: 36835101Free PMC Article
Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.
Salzano A, D'Assante R, Heaney LM, Monaco F, Rengo G, Valente P, Pasquali D, Bossone E, Gianfrilli D, Lenzi A, Cittadini A, Marra AM, Napoli R
Endocrine 2018 Aug;61(2):194-203. Epub 2018 Mar 23 doi: 10.1007/s12020-018-1584-6. PMID: 29572708
Telltale teeth: Idiopathic Hypergonadotropic Hypogonadism.
Lele GS, Lakade LS
J Indian Soc Pedod Prev Dent 2014 Jul-Sep;32(3):246-50. doi: 10.4103/0970-4388.135839. PMID: 25001446
Diagnosis of late puberty.
Argente J
Horm Res 1999;51 Suppl 3:95-100. doi: 10.1159/000053168. PMID: 10592450

Therapy

Pattern of Male Hypogonadism and Outcome of Treatment in South Rajasthan.
Sharma KR, Sharma H, Vishnoi J, Sharma RK, Goel S
J Assoc Physicians India 2022 Apr;70(4):11-12. PMID: 35443335
Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype.
Flannigan R, Patel P, Paduch DA
Sex Med Rev 2018 Oct;6(4):595-606. Epub 2018 Apr 19 doi: 10.1016/j.sxmr.2018.02.008. PMID: 29680294
Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.
Salzano A, D'Assante R, Heaney LM, Monaco F, Rengo G, Valente P, Pasquali D, Bossone E, Gianfrilli D, Lenzi A, Cittadini A, Marra AM, Napoli R
Endocrine 2018 Aug;61(2):194-203. Epub 2018 Mar 23 doi: 10.1007/s12020-018-1584-6. PMID: 29572708
49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.
Pamuk BO, Torun AN, Kulaksizoglu M, Algan C, Ertugrul DT, Yilmaz Z, Tutuncu NB, Demirag NG
Med Princ Pract 2009;18(6):482-5. Epub 2009 Sep 30 doi: 10.1159/000235899. PMID: 19797926
The child with micropenis.
Menon PS, Khatwa UA
Indian J Pediatr 2000 Jun;67(6):455-60. doi: 10.1007/BF02859468. PMID: 10932967

Prognosis

Clinical Peculiarities in a Cohort of Patients with Wolfram Syndrome 1.
Salzano G, Rigoli L, Valenzise M, Chimenz R, Passanisi S, Lombardo F
Int J Environ Res Public Health 2022 Jan 4;19(1) doi: 10.3390/ijerph19010520. PMID: 35010780Free PMC Article
Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.
Salzano A, D'Assante R, Heaney LM, Monaco F, Rengo G, Valente P, Pasquali D, Bossone E, Gianfrilli D, Lenzi A, Cittadini A, Marra AM, Napoli R
Endocrine 2018 Aug;61(2):194-203. Epub 2018 Mar 23 doi: 10.1007/s12020-018-1584-6. PMID: 29572708
Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients.
Accardo G, Vallone G, Esposito D, Barbato F, Renzullo A, Conzo G, Docimo G, Esposito K, Pasquali D
Asian J Androl 2015 Jan-Feb;17(1):154-8. doi: 10.4103/1008-682X.128514. PMID: 25130577Free PMC Article
The child with micropenis.
Menon PS, Khatwa UA
Indian J Pediatr 2000 Jun;67(6):455-60. doi: 10.1007/BF02859468. PMID: 10932967
Muscle pathology in Marinesco-Sjögren syndrome.
Komiyama A, Nonaka I, Hirayama K
J Neurol Sci 1989 Jan;89(1):103-13. doi: 10.1016/0022-510x(89)90010-5. PMID: 2522540

Clinical prediction guides

Pattern of Male Hypogonadism and Outcome of Treatment in South Rajasthan.
Sharma KR, Sharma H, Vishnoi J, Sharma RK, Goel S
J Assoc Physicians India 2022 Apr;70(4):11-12. PMID: 35443335
Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.
Carsote M, Capatina C, Valea A, Dumitrascu A
Arch Endocrinol Metab 2016 Feb;60(1):79-84. doi: 10.1590/2359-3997000000127. PMID: 26909487Free PMC Article
New case of Primrose syndrome with mild intellectual disability.
Posmyk R, Leśniewicz R, Chorąży M, Wołczyński S
Am J Med Genet A 2011 Nov;155A(11):2838-40. Epub 2011 Sep 9 doi: 10.1002/ajmg.a.34257. PMID: 21910247
49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.
Pamuk BO, Torun AN, Kulaksizoglu M, Algan C, Ertugrul DT, Yilmaz Z, Tutuncu NB, Demirag NG
Med Princ Pract 2009;18(6):482-5. Epub 2009 Sep 30 doi: 10.1159/000235899. PMID: 19797926
Linkage studies on Marinesco-Sjøgren syndrome and hypergonadotropic hypogonadism.
Skre H, Berg K
Clin Genet 1977 Jan;11(1):57-66. doi: 10.1111/j.1399-0004.1977.tb01279.x. PMID: 830450

Recent systematic reviews

Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype.
Flannigan R, Patel P, Paduch DA
Sex Med Rev 2018 Oct;6(4):595-606. Epub 2018 Apr 19 doi: 10.1016/j.sxmr.2018.02.008. PMID: 29680294

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