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Polyhydramnios, megalencephaly, and symptomatic epilepsy(PMSE)

MedGen UID:
370203
Concept ID:
C1970203
Disease or Syndrome
Synonyms: PMSE; PMSE SYNDROME
SNOMED CT: PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome (1167371007); Polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (1167371007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): STRADA (17q23.3)
 
Monarch Initiative: MONDO:0012611
OMIM®: 611087
Orphanet: ORPHA500533

Definition

A rare genetic neurological disorder with characteristics of pregnancy complicated by polyhydramnios, severe intractable epilepsy presenting in infancy, severe hypotonia, decreased muscle mass, global developmental delay, craniofacial dysmorphism (long face, large forehead, peaked eyebrows, broad nasal bridge, hypertelorism, large mouth with thick lips), and macrocephaly due to megalencephaly and hydrocephalus in most patients. Additional features that have been reported include cardiac anomalies like atrial septal defects, diabetes insipidus and nephrocalcinosis among others. [from SNOMEDCT_US]

Clinical features

From HPO
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Slender build
MedGen UID:
376828
Concept ID:
C1850573
Finding
Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.
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.
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.
Megalencephaly
MedGen UID:
65141
Concept ID:
C0221355
Congenital Abnormality
Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia).
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Astrocytosis
MedGen UID:
854483
Concept ID:
C3887640
Pathologic Function
Proliferation of astrocytes in the area of a lesion of the central nervous system.
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.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Facial hypotonia
MedGen UID:
336889
Concept ID:
C1845251
Finding
Reduced muscle tone of a muscle that is innervated by the facial nerve (the seventh cranial nerve).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Hyperplasia of midface
MedGen UID:
451009
Concept ID:
C0240309
Anatomical Abnormality
Abnormally anterior positioning of the infraorbital and perialar regions, or increased convexity of the face, or increased nasolabial angle. The midface includes the maxilla, the cheeks, the zygomas, and the infraorbital and perialar regions of the face
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Large forehead
MedGen UID:
326962
Concept ID:
C1839783
Finding
Thick upper lip vermilion
MedGen UID:
339521
Concept ID:
C1846423
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Diabetes insipidus
MedGen UID:
8349
Concept ID:
C0011848
Disease or Syndrome
A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPolyhydramnios, megalencephaly, and symptomatic epilepsy

Recent clinical studies

Etiology

Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA, Robinson DL, Hendrickson CL, Gottlieb S, Ramsay DA, Siu VM, Heuer GG, Crino PB, Morton DH
Brain 2007 Jul;130(Pt 7):1929-41. Epub 2007 May 23 doi: 10.1093/brain/awm100. PMID: 17522105

Diagnosis

Hutson J, Siu VM, Rupar CA
J Obstet Gynaecol Can 2022 Jul;44(7):798-802. Epub 2022 Feb 4 doi: 10.1016/j.jogc.2022.01.011. PMID: 35131504
Bi W, Glass IA, Muzny DM, Gibbs RA, Eng CM, Yang Y, Sun A
Am J Med Genet A 2016 Aug;170(8):2181-5. Epub 2016 May 12 doi: 10.1002/ajmg.a.37727. PMID: 27170158

Therapy

Ostendorf AP, Wong M
CNS Drugs 2015 Feb;29(2):91-9. doi: 10.1007/s40263-014-0223-x. PMID: 25633849Free PMC Article
Parker WE, Orlova KA, Parker WH, Birnbaum JF, Krymskaya VP, Goncharov DA, Baybis M, Helfferich J, Okochi K, Strauss KA, Crino PB
Sci Transl Med 2013 Apr 24;5(182):182ra53. doi: 10.1126/scitranslmed.3005271. PMID: 23616120Free PMC Article

Prognosis

Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA, Robinson DL, Hendrickson CL, Gottlieb S, Ramsay DA, Siu VM, Heuer GG, Crino PB, Morton DH
Brain 2007 Jul;130(Pt 7):1929-41. Epub 2007 May 23 doi: 10.1093/brain/awm100. PMID: 17522105

Clinical prediction guides

Bi W, Glass IA, Muzny DM, Gibbs RA, Eng CM, Yang Y, Sun A
Am J Med Genet A 2016 Aug;170(8):2181-5. Epub 2016 May 12 doi: 10.1002/ajmg.a.37727. PMID: 27170158
Parker WE, Orlova KA, Parker WH, Birnbaum JF, Krymskaya VP, Goncharov DA, Baybis M, Helfferich J, Okochi K, Strauss KA, Crino PB
Sci Transl Med 2013 Apr 24;5(182):182ra53. doi: 10.1126/scitranslmed.3005271. PMID: 23616120Free PMC Article
Orlova KA, Parker WE, Heuer GG, Tsai V, Yoon J, Baybis M, Fenning RS, Strauss K, Crino PB
J Clin Invest 2010 May;120(5):1591-602. Epub 2010 Apr 26 doi: 10.1172/JCI41592. PMID: 20424326Free PMC Article

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