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Neurodevelopmental disorder with microcephaly, hypotonia, and absent language(NEDMHAL)

MedGen UID:
1823989
Concept ID:
C5774216
Disease or Syndrome
Synonym: NEDMHAL
 
Gene (location): PSMB1 (6q27)
 
Monarch Initiative: MONDO:0859287
OMIM®: 620038

Definition

Neurodevelopmental disorder with microcephaly, hypotonia, and absent language (NEDMHAL) is a severe autosomal recessive disorder characterized by the constellation of these features. Behavioral problems and hearing loss are also present (Ansar et al., 2020). [from OMIM]

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
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\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\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\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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Professional guidelines

PubMed

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article

Recent clinical studies

Etiology

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Blum NJ, Bird LM, Stein MT
J Dev Behav Pediatr 2009 Feb;30(1):72-4. doi: 10.1097/DBP.0b013e3181976a83. PMID: 19218848
Smith A, Wiles C, Haan E, McGill J, Wallace G, Dixon J, Selby R, Colley A, Marks R, Trent RJ
J Med Genet 1996 Feb;33(2):107-12. doi: 10.1136/jmg.33.2.107. PMID: 8929945Free PMC Article

Diagnosis

Zhao A, Zhou R, Gu Q, Liu M, Zhang B, Huang J, Yang B, Yao R, Wang J, Lv H, Wang J, Shen Y, Wang H, Chen X
Clin Chim Acta 2021 Dec;523:10-18. Epub 2021 Aug 31 doi: 10.1016/j.cca.2021.08.030. PMID: 34478686
Blum NJ, Bird LM, Stein MT
J Dev Behav Pediatr 2009 Feb;30(1):72-4. doi: 10.1097/DBP.0b013e3181976a83. PMID: 19218848
Kivitie-Kallio S, Larsen A, Kajasto K, Norio R
Neuropediatrics 1999 Aug;30(4):181-9. doi: 10.1055/s-2007-973488. PMID: 10569209

Prognosis

Blum NJ, Bird LM, Stein MT
J Dev Behav Pediatr 2009 Feb;30(1):72-4. doi: 10.1097/DBP.0b013e3181976a83. PMID: 19218848
Smith A, Wiles C, Haan E, McGill J, Wallace G, Dixon J, Selby R, Colley A, Marks R, Trent RJ
J Med Genet 1996 Feb;33(2):107-12. doi: 10.1136/jmg.33.2.107. PMID: 8929945Free PMC Article

Clinical prediction guides

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Zhao A, Zhou R, Gu Q, Liu M, Zhang B, Huang J, Yang B, Yao R, Wang J, Lv H, Wang J, Shen Y, Wang H, Chen X
Clin Chim Acta 2021 Dec;523:10-18. Epub 2021 Aug 31 doi: 10.1016/j.cca.2021.08.030. PMID: 34478686
Blum NJ, Bird LM, Stein MT
J Dev Behav Pediatr 2009 Feb;30(1):72-4. doi: 10.1097/DBP.0b013e3181976a83. PMID: 19218848
Kivitie-Kallio S, Larsen A, Kajasto K, Norio R
Neuropediatrics 1999 Aug;30(4):181-9. doi: 10.1055/s-2007-973488. PMID: 10569209

Recent systematic reviews

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article

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