Clinical Guidance
To date, fewer than 50 individuals have been identified with a pathogenic variant in PPP2R1A [, , , , ]. The following description of the phenotypic features associated with this condition is based on comprehensive clinical observations of individuals with confirmed pathogenic variants. Table 2. Select Features of PPP2R1A-Related Neurodevelopmental Disorder
Feature | # of Persons w/Feature / # Assessed | Comment |
|---|
Developmental delay | 37/37 (100%) | Ranging from mild to profound |
Language delay | 37/37 (100%) | Some persons remain nonverbal. |
Intellectual disability | 36/37 (97%) | Ranging from mild to profound, usually moderate to severe |
Delayed walking | 28/30 (93%) | Some persons remain nonambulatory. |
Hypotonia | 32/35 (91%) | Persistent into childhood adulthood in 2 known persons |
Corpus callosum hypo-/aplasia | 22/33 (67%) | — |
Head growth abnormalities | 22/36 (61%) | — |
Macrocephaly | 12/36 (33%) | See . |
Microcephaly | 10/36 (28%) Feeding difficulties | 15/30 (50%) |
Epilepsy | 17/35 (49%) | See . |
Ventriculomegaly | 14/33 (42%) | Incl hydrocephalus |
Joint hypermobility | 14/37 (38%) | — |
External ear abnormalities | 11/37 (30%) | Incl microtia |
Scoliosis | 9/37 (24%) | — |
Delayed myelination | 6/33 (18%) | — |
Hypoplasia of cerebellum/ brain stem | 5/33 (15%) | — |
Periventricular leukomalacia | 4/33 (12%) | — |
Hearing loss | 4/37 (11%) | Incl sensorineural hearing loss assoc w/microtia |
Short stature | 3/37 (8%) | — |
Persistent ductus arteriosus | 3/37 (8%) | Developmental delay (DD) and intellectual disability (ID). The degree of DD is variable, but often in the moderate-to-severe range. DD in most affected individuals is global, affecting both cognitive and motor skills, but speech and language development and walking appear to be especially delayed. |
Source: GeneReviews — "PPP2R1A-Related Neurodevelopmental Disorder"
