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Neurodevelopmental disorder with poor language and loss of hand skills(NDPLHS)

MedGen UID:
1637031
Concept ID:
C4693546
Disease or Syndrome
Synonyms: NDPLHS; NEURODEVELOPMENTAL DISORDER WITH POOR LANGUAGE AND LOSS OF HAND SKILLS
 
Gene (location): GABBR2 (9q22.33)
 
Monarch Initiative: MONDO:0060659
OMIM®: 617903

Definition

NDPLHS is an autosomal dominant disorder characterized by developmental stagnation or regression apparent in the first years of life and manifest as loss of purposeful hand movements, loss of language, and intellectual disability. Additional features may include stereotypic movements, dystonia, gait abnormalities, sleep disturbances, and small hands and feet. The phenotype is reminiscent of Rett syndrome (RTT; 312750) (summary by Yoo et al., 2017). [from OMIM]

Clinical features

From HPO
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Bruxism
MedGen UID:
676
Concept ID:
C0006325
Mental or Behavioral Dysfunction
Bruxism is characterized by the grinding of the teeth including the clenching of the jaw and typically occur during sleep, but also can occcur while the affected individual is awake.
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep disturbance
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
An abnormality of sleep including such phenomena as 1) insomnia/hypersomnia, 2) non-restorative sleep, 3) sleep schedule disorder, 4) excessive daytime somnolence, 5) sleep apnea, and 6) restlessness.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of exceeding restlessness and excessive motor activity associated with mental distress or a feeling of inner tension.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Hyperventilation
MedGen UID:
9377
Concept ID:
C0020578
Finding
Hyperventilation refers to an increased pulmonary ventilation rate that is faster than necessary for the exchange of gases. Hyperventilation can result from increased frequency of breathing, an increased tidal volume, or both, and leads to an excess intake of oxygen and the blowing off of carbon dioxide.

Recent clinical studies

Etiology

Rashid SMU, Mukherjee D, Ahmmed AU
Int J Pediatr Otorhinolaryngol 2018 Nov;114:51-60. Epub 2018 Jul 31 doi: 10.1016/j.ijporl.2018.07.054. PMID: 30262367

Diagnosis

Rashid SMU, Mukherjee D, Ahmmed AU
Int J Pediatr Otorhinolaryngol 2018 Nov;114:51-60. Epub 2018 Jul 31 doi: 10.1016/j.ijporl.2018.07.054. PMID: 30262367

Clinical prediction guides

D'Onofrio G, Riva A, Di Rosa G, Cali' E, Efthymiou S, Gitto E, Madia F, Accogli A, Zara F, Houlden H, Salpietro V, Striano P, Soler D
Brain Dev 2022 Aug;44(7):469-473. Epub 2022 Apr 9 doi: 10.1016/j.braindev.2022.03.010. PMID: 35414446

Supplemental Content

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