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Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis(NEDMSC)

MedGen UID:
1794262
Concept ID:
C5562052
Disease or Syndrome
Synonyms: NEDMSC; NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND NEONATAL CHOLESTASIS
 
Gene (location): VPS50 (7q21.2-21.3)
 
Monarch Initiative: MONDO:0859216
OMIM®: 619685

Definition

Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis (NEDMSC) is an autosomal recessive disorder characterized by severely impaired global development apparent from infancy, progressive microcephaly, and neonatal cholestasis manifest as jaundice and elevated liver enzymes. The liver disease resolves, but affected individuals show feeding difficulties, failure to thrive, hypotonia, seizures, hyperkinetic movements, irritability, and poor eye contact or vision, and achieve almost no motor or cognitive developmental milestones. Brain imaging demonstrates agenesis or hypoplasia of the corpus callosum. Death in early childhood may occur (summary by Schneeberger et al., 2021). [from OMIM]

Clinical features

From HPO
Bilateral cryptorchidism
MedGen UID:
96568
Concept ID:
C0431663
Congenital Abnormality
Absence of both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.
Mild proteinuria
MedGen UID:
868438
Concept ID:
C4022832
Finding
Mildly increased levels of protein in the urine (150-500 mg per day in adults).
Intrahepatic cholestasis
MedGen UID:
3042
Concept ID:
C0008372
Disease or Syndrome
Impairment of bile flow due to obstruction in the small bile ducts within the liver.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Nasogastric tube feeding
MedGen UID:
847783
Concept ID:
C3853581
Medical Device
The condition of inability to eat normally treated by placement of a thin tube through the nose into the stomach that is then used to carry food.
Opisthotonus
MedGen UID:
56246
Concept ID:
C0151818
Sign or Symptom
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Generalized tonic seizure
MedGen UID:
322935
Concept ID:
C1836508
Disease or Syndrome
A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Increased serum bile acid concentration
MedGen UID:
868605
Concept ID:
C4023004
Finding
An increase in the concentration of bile acid in the blood.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Esodeviation
MedGen UID:
1641033
Concept ID:
C4551734
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally.

Recent clinical studies

Diagnosis

Schneeberger PE, Nampoothiri S, Holling T, Yesodharan D, Alawi M, Knisely AS, Müller T, Plecko B, Janecke AR, Kutsche K
Brain 2021 Nov 29;144(10):3036-3049. doi: 10.1093/brain/awab206. PMID: 34037727

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