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Pontocerebellar hypoplasia, type 16(PCH16)

MedGen UID:
1794197
Concept ID:
C5561987
Disease or Syndrome
Synonym: Pontocerebellar hypoplasia, type 16
 
Gene (location): MINPP1 (10q23.2)
 
Monarch Initiative: MONDO:0030438
OMIM®: 619527

Definition

Pontocerebellar hypoplasia type 16 (PCH16) is an autosomal recessive severe neurodevelopmental disorder characterized by hypotonia and severe global developmental delay apparent from early infancy. Although the severity of the disorder is variable, most affected individuals achieve only a few, if any, developmental milestones. Most are unable to walk or speak, have eye abnormalities with poor visual contact, and develop early-onset epilepsy. Other features may include stereotypic movements, spasticity, and progressive microcephaly. Brain imaging shows pontocerebellar hypoplasia, often with thin corpus callosum, atrophy of the thalamus and basal ganglia, enlarged ventricles, and white matter abnormalities (summary by Ucuncu et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596). [from OMIM]

Clinical features

From HPO
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
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.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Hypoplasia of the pons
MedGen UID:
341246
Concept ID:
C1848529
Finding
Underdevelopment of the pons.
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.
Delayed fine motor development
MedGen UID:
869257
Concept ID:
C4023681
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
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.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Recent clinical studies

Etiology

Burglen L, Chantot-Bastaraud S, Garel C, Milh M, Touraine R, Zanni G, Petit F, Afenjar A, Goizet C, Barresi S, Coussement A, Ioos C, Lazaro L, Joriot S, Desguerre I, Lacombe D, des Portes V, Bertini E, Siffroi JP, de Villemeur TB, Rodriguez D
Orphanet J Rare Dis 2012 Mar 27;7:18. doi: 10.1186/1750-1172-7-18. PMID: 22452838Free PMC Article
Graham JM Jr, Spencer AH, Grinberg I, Niesen CE, Platt LD, Maya M, Namavar Y, Baas F, Dobyns WB
Am J Med Genet A 2010 Sep;152A(9):2268-76. doi: 10.1002/ajmg.a.33579. PMID: 20803644Free PMC Article

Diagnosis

Nicolle R, Altin N, Siquier-Pernet K, Salignac S, Blanc P, Munnich A, Bole-Feysot C, Malan V, Caron B, Nitschké P, Desguerre I, Boddaert N, Rio M, Rausell A, Cantagrel V
BMC Med Genomics 2023 Jun 21;16(1):143. doi: 10.1186/s12920-023-01582-z. PMID: 37344844Free PMC Article
Rodríguez-García ME, Cotrina-Vinagre FJ, Bellusci M, Merino-López A, Chumilla-Calzada S, García-Silva MT, Martínez-Azorín F
Neuromuscul Disord 2021 Aug;31(8):773-782. Epub 2021 May 28 doi: 10.1016/j.nmd.2021.05.008. PMID: 34210538
Ammann-Schnell L, Groeschel S, Kehrer C, Frölich S, Krägeloh-Mann I
Orphanet J Rare Dis 2021 May 10;16(1):211. doi: 10.1186/s13023-021-01828-y. PMID: 33971942Free PMC Article
Graham JM Jr, Spencer AH, Grinberg I, Niesen CE, Platt LD, Maya M, Namavar Y, Baas F, Dobyns WB
Am J Med Genet A 2010 Sep;152A(9):2268-76. doi: 10.1002/ajmg.a.33579. PMID: 20803644Free PMC Article
Barth PG, Blennow G, Lenard HG, Begeer JH, van der Kley JM, Hanefeld F, Peters AC, Valk J
Neurology 1995 Feb;45(2):311-7. doi: 10.1212/wnl.45.2.311. PMID: 7854532

Prognosis

Nicolle R, Altin N, Siquier-Pernet K, Salignac S, Blanc P, Munnich A, Bole-Feysot C, Malan V, Caron B, Nitschké P, Desguerre I, Boddaert N, Rio M, Rausell A, Cantagrel V
BMC Med Genomics 2023 Jun 21;16(1):143. doi: 10.1186/s12920-023-01582-z. PMID: 37344844Free PMC Article
Ammann-Schnell L, Groeschel S, Kehrer C, Frölich S, Krägeloh-Mann I
Orphanet J Rare Dis 2021 May 10;16(1):211. doi: 10.1186/s13023-021-01828-y. PMID: 33971942Free PMC Article

Clinical prediction guides

Nicolle R, Altin N, Siquier-Pernet K, Salignac S, Blanc P, Munnich A, Bole-Feysot C, Malan V, Caron B, Nitschké P, Desguerre I, Boddaert N, Rio M, Rausell A, Cantagrel V
BMC Med Genomics 2023 Jun 21;16(1):143. doi: 10.1186/s12920-023-01582-z. PMID: 37344844Free PMC Article
Ammann-Schnell L, Groeschel S, Kehrer C, Frölich S, Krägeloh-Mann I
Orphanet J Rare Dis 2021 May 10;16(1):211. doi: 10.1186/s13023-021-01828-y. PMID: 33971942Free PMC Article
Burglen L, Chantot-Bastaraud S, Garel C, Milh M, Touraine R, Zanni G, Petit F, Afenjar A, Goizet C, Barresi S, Coussement A, Ioos C, Lazaro L, Joriot S, Desguerre I, Lacombe D, des Portes V, Bertini E, Siffroi JP, de Villemeur TB, Rodriguez D
Orphanet J Rare Dis 2012 Mar 27;7:18. doi: 10.1186/1750-1172-7-18. PMID: 22452838Free PMC Article

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