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Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities(NEDPBA)

MedGen UID:
1857802
Concept ID:
C5935590
Disease or Syndrome
Synonyms: NEDPBA; NEURODEVELOPMENTAL DISORDER WITH EARLY-ONSET PARKINSONISM AND BEHAVIORAL ABNORMALITIES
 
Gene (location): PTRHD1 (2p23.3)
 
Monarch Initiative: MONDO:0958323
OMIM®: 620747

Definition

Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities (NEDPBA) is an autosomal recessive disorder characterized by delayed developmental milestones apparent in late infancy or early childhood, impaired intellectual development with learning difficulties, and behavioral abnormalities. Motor abnormalities, including parkinsonism and spasticity, usually develop in the third or fourth decades, although earlier onset has been reported. Some patients have seizures. There is inter- and intrafamilial variability (Kuipers et al., 2018; Al-Kasbi et al., 2021). [from OMIM]

Clinical features

From HPO
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
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.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Shuffling gait
MedGen UID:
68545
Concept ID:
C0231688
Finding
A type of gait (walking) characterized by by dragging one's feet along or without lifting the feet fully from the ground.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Resting tremor
MedGen UID:
66697
Concept ID:
C0234379
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Short attention span
MedGen UID:
82652
Concept ID:
C0262630
Finding
Reduced attention span characterized by distractibility and impulsivity.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Freezing of gait
MedGen UID:
678586
Concept ID:
C0860515
Finding
Freezing of gait is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk.
Hypersomnia
MedGen UID:
214588
Concept ID:
C0917799
Disease or Syndrome
Excessive sleepiness or feeling of sleepiness, or difficulty staying awake despite having had adequate sleep, which persists over several days.
Froment sign
MedGen UID:
713325
Concept ID:
C1290999
Sign or Symptom
An abnormal result of a physical examination of the the hand that tests for palsy of the ulnar nerve. This nerve innervates the adductor pollicis and interossei muscles and thereby enables adduction of the thumb and extension of the interphalangeal joint. An abnormal result consists in reduced functionality and muscular weakness in the pinch grip between the thumb and index finger of the affected hand as the patient attempts to pinch a piece of paper that the examiner tries to pull away. The flexor pollicis longus muscle tries to compensate for the weakness by flexing the tip of the thumb at the interphalangeal joint.
Sensory axonal neuropathy
MedGen UID:
334116
Concept ID:
C1842587
Finding
An axonal neuropathy of peripheral sensory nerves.
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
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.
Restlessness
MedGen UID:
854457
Concept ID:
C3887611
Sign or Symptom
A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior.
Amplification of sexual behavior
MedGen UID:
1853285
Concept ID:
C5873000
Finding
An abnormal increase of libido (sexual desire), typically accompanied by a higher frequency of sexual activity compared to from a person's previous norm.
Cogwheel rigidity
MedGen UID:
57469
Concept ID:
C0151564
Sign or Symptom
A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched).
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Mask-like facies
MedGen UID:
140860
Concept ID:
C0424448
Finding
A lack of facial expression often with staring eyes and a slightly open mouth.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.

Recent clinical studies

Etiology

Sumitomo A, Horike K, Hirai K, Butcher N, Boot E, Sakurai T, Nucifora FC Jr, Bassett AS, Sawa A, Tomoda T
Sci Adv 2018 Aug;4(8):eaar6637. Epub 2018 Aug 15 doi: 10.1126/sciadv.aar6637. PMID: 30116778Free PMC Article
Loesch D, Hagerman R
Adv Exp Med Biol 2012;769:78-114. doi: 10.1007/978-1-4614-5434-2_6. PMID: 23560306Free PMC Article

Diagnosis

Vargas AP, Carod-Artal FJ, Bomfim D, Vázquez-Cabrera C, Dantas-Barbosa C
J Child Neurol 2003 Jun;18(6):429-32. doi: 10.1177/08830738030180061301. PMID: 12886981

Therapy

Loesch D, Hagerman R
Adv Exp Med Biol 2012;769:78-114. doi: 10.1007/978-1-4614-5434-2_6. PMID: 23560306Free PMC Article

Prognosis

Vargas AP, Carod-Artal FJ, Bomfim D, Vázquez-Cabrera C, Dantas-Barbosa C
J Child Neurol 2003 Jun;18(6):429-32. doi: 10.1177/08830738030180061301. PMID: 12886981

Clinical prediction guides

Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article

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