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Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis(NEDSPLB)

MedGen UID:
899982
Concept ID:
C4225295
Disease or Syndrome
Synonym: NEDSPLB
 
Gene (location): PI4KA (22q11.21)
 
Monarch Initiative: MONDO:0014679
OMIM®: 616531

Disease characteristics

Excerpted from the GeneReview: PI4KA-Related Disorder
PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria. [from GeneReviews]
Authors:
Emma L Baple  |  Claire Salter  |  Holm Uhlig, et. al.   view full author information

Additional description

From OMIM
Neurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities (NEDSPLB) is a severe autosomal recessive disorder characterized by global developmental delay with impaired intellectual development and poor or absent speech, axial hypotonia, and peripheral spasticity and hyperreflexia. Affected individuals may have feeding difficulties with gastroesophageal reflux and poor overall growth, as well as microcephaly and nonspecific dysmorphic facial features. Additional features may include nystagmus, inability to walk, ataxia, abnormal movements, and seizures. Brain imaging shows hypomyelination with decreased white matter volume, cerebral and cerebellar atrophy, and thin corpus callosum. Polymicrogyria may be observed in rare cases. Some patients have a primary immunodeficiency or gastrointestinal disturbances similar to inflammatory bowel disease (summary by Verdura et al., 2021, Salter et al., 2021).  http://www.omim.org/entry/616531

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Overlapping fingers
MedGen UID:
252954
Concept ID:
C1446712
Finding
A finger resting on the dorsal surface of an adjacent digit when the hand is at rest.
Femoral retroversion
MedGen UID:
375866
Concept ID:
C1846339
Congenital Abnormality
An abnormal backward rotation of the hip relative to the knee such that the hips are externally rotated with the foot pointed outward instead of straight ahead (out-toeing).
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.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Cerebellar dysplasia
MedGen UID:
479952
Concept ID:
C3278322
Finding
Cerebellar dysplasia (abnormal growth or development) is defined by abnormal cerebellar foliation, white matter arborization, and gray-white matter junction. Cerebellar dysplasia is a neuroimaging finding that describes abnormalities of both the cerebellar cortex and white matter and is associated with variable neurodevelopmental outcome. Dysplasia may globally involve the cerebellum or affect only one cerebellar hemisphere. In addition, cerebellar dysplasia may be associated with cortical/subcortical cysts.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Perisylvian polymicrogyria
MedGen UID:
481305
Concept ID:
C3279675
Finding
Polymicrogyria (an excessive number of small gyri or convolutions) that is maximal in perisylvian regions (the regions that surround the Sylvian fissures), which may be symmetric or asymmetric and may extend beyond perisylvian regions. The Sylvian fissures often extend posteriorly and superiorly.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Unilateral wrist flexion contracture
MedGen UID:
892557
Concept ID:
C4022898
Finding
A chronic loss of wrist joint motion on one side only.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Absent uvula
MedGen UID:
75599
Concept ID:
C0266121
Congenital Abnormality
Lack of the uvula.
Fetal pyelectasis
MedGen UID:
384527
Concept ID:
C2317073
Disease or Syndrome
Mild pyelectasis is defined as a hypoechoic spherical or elliptical space within the renal pelvis that measures at least 5mm and not more than 10 mm. The measurement is taken on a transverse section through the fetal renal pelvis using the maximum anterior-to-posterior measurement.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Prognosis

Pagnamenta AT, Howard MF, Wisniewski E, Popitsch N, Knight SJ, Keays DA, Quaghebeur G, Cox H, Cox P, Balla T, Taylor JC, Kini U
Hum Mol Genet 2015 Jul 1;24(13):3732-41. Epub 2015 Apr 8 doi: 10.1093/hmg/ddv117. PMID: 25855803Free PMC Article

Clinical prediction guides

Pagnamenta AT, Howard MF, Wisniewski E, Popitsch N, Knight SJ, Keays DA, Quaghebeur G, Cox H, Cox P, Balla T, Taylor JC, Kini U
Hum Mol Genet 2015 Jul 1;24(13):3732-41. Epub 2015 Apr 8 doi: 10.1093/hmg/ddv117. PMID: 25855803Free PMC Article

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