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Hypothyroidism, congenital, nongoitrous, 8(CHNG8)

MedGen UID:
1684717
Concept ID:
C5231395
Disease or Syndrome
Synonyms: CHNG8; HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 8
 
Gene (location): TBL1X (Xp22.31-22.2)
 
Monarch Initiative: MONDO:0026731
OMIM®: 301033

Definition

Congenital nongoitrous hypothyroidism-8 (CHNG8) is characterized by relatively mild central hypothyroidism, which may be accompanied by hearing loss in some patients (Heinen et al., 2016). [from OMIM]

Clinical features

From HPO
Secondary amenorrhea
MedGen UID:
115919
Concept ID:
C0232940
Disease or Syndrome
The cessation of menstruation for six months or more in a female that is not pregnant, breastfeeding or menopausal.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diminished ability to concentrate
MedGen UID:
65900
Concept ID:
C0235198
Finding
The inability to focus or concentrate on a specific task, activity, or object. The subject may find themselves unable to grasp or understand written text and re-reads frequently without understanding. Familiar tasks or activities are severely compromised due to the lack of ability to concentrate. Thinking through multi-step problems is typically very difficult or impossible, leading to avoidance of such activities.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Central hypothyroidism
MedGen UID:
488836
Concept ID:
C0271801
Disease or Syndrome
A type of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland. Central hypothyroidism is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects.
Inappropriately normal thyroid-stimulating hormone level
MedGen UID:
1691608
Concept ID:
C5232538
Finding
A normal or elevated serum thyroid-stimulating hormone (TSH) level in the face of an elevation in circulating FT4 and/or FT3.
Decreased circulating free T4 concentration
MedGen UID:
1743550
Concept ID:
C5421592
Finding
A reduced concentration of free thyroxine (fT4) in the blood circulation.

Recent clinical studies

Etiology

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
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
Joergensen JV, Oerbeck B, Jebsen P, Heyerdahl S, Kase BF
Acta Paediatr 2005 Aug;94(8):1049-54. doi: 10.1111/j.1651-2227.2005.tb02044.x. PMID: 16188848
Desai MP
Indian J Pediatr 1997 Jan-Feb;64(1):11-20. doi: 10.1007/BF02795771. PMID: 10771808

Diagnosis

Joergensen JV, Oerbeck B, Jebsen P, Heyerdahl S, Kase BF
Acta Paediatr 2005 Aug;94(8):1049-54. doi: 10.1111/j.1651-2227.2005.tb02044.x. PMID: 16188848
Desai MP
Indian J Pediatr 1997 Jan-Feb;64(1):11-20. doi: 10.1007/BF02795771. PMID: 10771808
Connors MH, Styne DM
Pediatrics 1986 Aug;78(2):287-90. PMID: 2874542

Therapy

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
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
Joergensen JV, Oerbeck B, Jebsen P, Heyerdahl S, Kase BF
Acta Paediatr 2005 Aug;94(8):1049-54. doi: 10.1111/j.1651-2227.2005.tb02044.x. PMID: 16188848
Connors MH, Styne DM
Pediatrics 1986 Aug;78(2):287-90. PMID: 2874542

Prognosis

Joergensen JV, Oerbeck B, Jebsen P, Heyerdahl S, Kase BF
Acta Paediatr 2005 Aug;94(8):1049-54. doi: 10.1111/j.1651-2227.2005.tb02044.x. PMID: 16188848
Desai MP
Indian J Pediatr 1997 Jan-Feb;64(1):11-20. doi: 10.1007/BF02795771. PMID: 10771808
Connors MH, Styne DM
Pediatrics 1986 Aug;78(2):287-90. PMID: 2874542

Clinical prediction guides

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
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
Grasberger H, Vaxillaire M, Pannain S, Beck JC, Mimouni-Bloch A, Vatin V, Vassart G, Froguel P, Refetoff S
Hum Genet 2005 Dec;118(3-4):348-55. Epub 2005 Sep 28 doi: 10.1007/s00439-005-0036-6. PMID: 16189712
Connors MH, Styne DM
Pediatrics 1986 Aug;78(2):287-90. PMID: 2874542

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