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Pontocerebellar hypoplasia, type 15(PCH15)

MedGen UID:
1781311
Concept ID:
C5543326
Disease or Syndrome
Synonyms: PCH15; PONTOCEREBELLAR HYPOPLASIA, TYPE 15
 
Gene (location): CDC40 (6q21)
 
Monarch Initiative: MONDO:0030259
OMIM®: 619302

Definition

Pontocerebellar hypoplasia type 15 (PCH15) is a severe autosomal recessive neurodevelopmental disorder characterized by congenital onset of progressive microcephaly and poor or absent psychomotor development with severely impaired intellectual development apparent from birth. Other features may include spastic quadriplegia, early-onset seizures, and chronic anemia and thrombocytopenia. Brain imaging shows pontocerebellar hypoplasia and partial agenesis of the corpus callosum (summary by et al., 2021). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596). [from OMIM]

Clinical features

From HPO
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.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
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.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
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.
Partial agenesis of the corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
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 brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Delayed early-childhood social milestone development
MedGen UID:
868509
Concept ID:
C4022906
Finding
A failure to meet one or more age-related milestones of social behavior.
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.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
Chronic neutropenia
MedGen UID:
1671095
Concept ID:
C0746882
Disease or Syndrome
Neutropenia with an absolute neutrophil count (ANC) less than 1,500,000,000/L lasting for more than 3 months.

Professional guidelines

PubMed

Kahn-Kirby AH, Amagata A, Maeder CI, Mei JJ, Sideris S, Kosaka Y, Hinman A, Malone SA, Bruegger JJ, Wang L, Kim V, Shrader WD, Hoff KG, Latham JC, Ashley EA, Wheeler MT, Bertini E, Carrozzo R, Martinelli D, Dionisi-Vici C, Chapman KA, Enns GM, Gahl W, Wolfe L, Saneto RP, Johnson SC, Trimmer JK, Klein MB, Holst CR
PLoS One 2019;14(3):e0214250. Epub 2019 Mar 28 doi: 10.1371/journal.pone.0214250. PMID: 30921410Free PMC Article

Recent clinical studies

Etiology

Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
Arslan EA, Öncel İ, Ceylan AC, Topçu M, Topaloğlu H
Brain Dev 2020 Jan;42(1):6-18. Epub 2019 Sep 4 doi: 10.1016/j.braindev.2019.08.004. PMID: 31493945
Boddaert N, Desguerre I, Bahi-Buisson N, Romano S, Valayannopoulos V, Saillour Y, Seidenwurm D, Grevent D, Berteloot L, Lebre AS, Zilbovicius M, Puget S, Salomon R, Attie-Bitach T, Munnich A, Brunelle F, de Lonlay P
J Neuroradiol 2010 Oct;37(4):220-30. Epub 2010 Apr 7 doi: 10.1016/j.neurad.2009.12.009. PMID: 20378176
Steinlin M, Klein A, Haas-Lude K, Zafeiriou D, Strozzi S, Müller T, Gubser-Mercati D, Schmitt Mechelke T, Krägeloh-Mann I, Boltshauser E
Eur J Paediatr Neurol 2007 May;11(3):146-52. Epub 2007 Feb 22 doi: 10.1016/j.ejpn.2006.11.012. PMID: 17320436
Barth PG
Brain Dev 1993 Nov-Dec;15(6):411-22. doi: 10.1016/0387-7604(93)90080-r. PMID: 8147499

Diagnosis

Arslan EA, Öncel İ, Ceylan AC, Topçu M, Topaloğlu H
Brain Dev 2020 Jan;42(1):6-18. Epub 2019 Sep 4 doi: 10.1016/j.braindev.2019.08.004. PMID: 31493945
Sanefuji M, Kira R, Matsumoto K, Gondo K, Torisu H, Kawakami H, Iwaki T, Hara T
J Child Neurol 2010 Nov;25(11):1429-34. Epub 2010 Jun 17 doi: 10.1177/0883073810372991. PMID: 20558670
Boddaert N, Desguerre I, Bahi-Buisson N, Romano S, Valayannopoulos V, Saillour Y, Seidenwurm D, Grevent D, Berteloot L, Lebre AS, Zilbovicius M, Puget S, Salomon R, Attie-Bitach T, Munnich A, Brunelle F, de Lonlay P
J Neuroradiol 2010 Oct;37(4):220-30. Epub 2010 Apr 7 doi: 10.1016/j.neurad.2009.12.009. PMID: 20378176
Guillot N, Cuisset JM, Cuvellier JC, Hurtevent JF, Joriot S, Vallee L
Brain Dev 2008 Mar;30(3):169-78. Epub 2007 Sep 4 doi: 10.1016/j.braindev.2007.07.008. PMID: 17804187
Grellner W, Rohde K, Wilske J
Forensic Sci Int 2000 Sep 11;113(1-3):165-72. doi: 10.1016/s0379-0738(00)00270-x. PMID: 10978619

Prognosis

Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
Arslan EA, Öncel İ, Ceylan AC, Topçu M, Topaloğlu H
Brain Dev 2020 Jan;42(1):6-18. Epub 2019 Sep 4 doi: 10.1016/j.braindev.2019.08.004. PMID: 31493945
Sanefuji M, Kira R, Matsumoto K, Gondo K, Torisu H, Kawakami H, Iwaki T, Hara T
J Child Neurol 2010 Nov;25(11):1429-34. Epub 2010 Jun 17 doi: 10.1177/0883073810372991. PMID: 20558670
Grellner W, Rohde K, Wilske J
Forensic Sci Int 2000 Sep 11;113(1-3):165-72. doi: 10.1016/s0379-0738(00)00270-x. PMID: 10978619

Clinical prediction guides

Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
Arslan EA, Öncel İ, Ceylan AC, Topçu M, Topaloğlu H
Brain Dev 2020 Jan;42(1):6-18. Epub 2019 Sep 4 doi: 10.1016/j.braindev.2019.08.004. PMID: 31493945
Grellner W, Rohde K, Wilske J
Forensic Sci Int 2000 Sep 11;113(1-3):165-72. doi: 10.1016/s0379-0738(00)00270-x. PMID: 10978619

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