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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 occur 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 characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
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.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Inappropriate crying
MedGen UID:
810697
Concept ID:
C0860609
Sign or Symptom
Uncontrolled episodes of crying occur without any apparent motivating stimuli.
Circadian rhythm sleep disorder
MedGen UID:
167920
Concept ID:
C0877792
Pathologic Function
Any abnormality of an individual's circadian rhythm that affects the timing of sleeping and being awake is referred to as a sleep-wake disorder.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Developmental stagnation
MedGen UID:
341348
Concept ID:
C1848980
Finding
A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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
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.
Recurrent hand flapping
MedGen UID:
867996
Concept ID:
C4022387
Mental or Behavioral Dysfunction
A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically.
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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