Table 1 Clinical presentation of patients with PPP2R5D variants

Maines et al. (2021)

c.592G > A

p.(Glu198Lys)

Developmental delay, Seizures, Hypotonia

Epicanthus and wide forehead, Nystagmus

Hypoglycemia, Macrocephaly with wide open anterior fontanel, Two hemangiomas on the lower lip and the back, Vomiting

Yan et al. (2021)

c.620G > T

p.(Trp207Leu)

GDD, ID, Hypotonia, speech impairment, and behavioral abnormality

Prominent forehead, Open mouth

Macrocephaly, Hypoplastic corpus callosum, Temporal lobe parenchymal atrophy, Enlargement of the ventricular system, Retardation of myelination of white matter

Madaan et al. (2022)

c.592G > A

p.(Glu198Lys)

GDD, Epileptic encephalopathy, Frequent myoclonic seizures, Central hypotonia

Elongated facies, Temporal hollowing, Open mouth

Macrocephaly, Enlarged Virchow–Robin spaces, Delay in social, adaptive, and language, Poor eye contact, communicative abilities, and motor stereotypes

Walker et al. (2021)

c.748G > A

p.(Glu250Lys)

GDD, Moderate ID, ADHD, Early-onset parkinsonism, Left rest tremor, and bradykinesia

Latter—left rest tremor and bradykinesia that led to the diagnosis of

Parkinson’s disease (PD)

Macrocephaly, Hydrocephalus, Aqueductal stenosis, Auditory disorder

Hetzelt et al. (2021)

c.592G > A

p.(Glu198Lys)

ID, muscular hypotonia and dystonia, seizures, progressive motor decline, and early-onset levodopa-responsive parkinsonism

Long face and a tent-shape upper lip

Macrocephaly

Kim et al. (2020)

(Duplicate case here reported in Loveday et al. (2015))

c.598G > A

p.(Glu200Lys)

Mild developmental motor and language delay, Mild ID, Gait difficulty and bradykinesia, Levodopa-responsive early-onset parkinsonism

White matter hyperintensities, Hypertension, and diabetes mellitus

c.598G > A

p.(Glu200Lys)

ID, Rest tremor and myoclonus, Akinetic rigid parkinsonism. Early-onset non-motor features of Levodopa-responsive parkinsonism

Relative paucity of white matter signal abnormality

c.598G > A

p.(Glu200Lys)

Motor developmental delay and language acquisition, Mild ID, Rest tremor and incoordination, Early-onset Levodopa-responsive parkinsonism, Dyskinesia

Overgrowth

Yeung et al. (2017)

c.592G > A

p.(Glu198Lys)

Moderate GDD,

Mild ID, Autism, Epilepsy, Hypotonia

Hypertelorism, Frontal bossing

Megalencephaly

c.592G > A

p.(Glu198Lys)

Moderate GDD, Mild ID, Suspected autism, Epilepsy

Hypertelorism, Frontal bossing

Megalencephaly

Shang et al. (2016)

c.592G > A

p.(Glu198Lys)

GDD, ID, Autism, Anxiety

Downslanting palpebral fissures, Dolichocephaly

Scoliosis, Myopia, Macrocephaly

c.592G > A

p.(Glu198Lys)

GDD, ID, Autism, Seizures, Hypotonia, Non-verbal

Prominent forehead, Large anterior fontanelle, Mild midface hypoplasia

Failure to thrive, Possible short stature, Macrocephaly, Bilateral small arachnoid cysts, Cavum septum pellucidum

c.598G > A

p.(Glu200Lys)

GDD, ID, Autism, Hypotonia, Water fascination, Licks items, Excitable, Nystagmus

Plagiocephaly, Triangular face, Long philtrum, Short nose, Thin upper lip, Midface hypoplasia, Slightly low set ears, Cleft palate

Torticollis, Pectus carinatum, Clinodactyly and malformation of toes, Rotational delayed visual maturation, Atrial and ventricular septal defects, Bicuspid aortic valve, Short stature, Easy bruising

c.1258G > A

p.(Glu420Lys)

GDD, ID, Autism, Hypotonia, Non-verbal, Aggressive, Stereotypies, Impulse control issues, Ataxia, Wide-based gait, Absent deep tendon reflexes

Alternating esotropia, Macrocephaly, Prominent CSF spaces, Mildly enlarged lateral ventricles, Cavum septum, Cavum verge

c.1258G > A

p.(Glu420Lys)

GDD, Hypotonia

Prominent forehead, Slightly low-set ears, High-arched palate, Small nose

Strabismus, Ventricular septal defect, Patent foramen oval, Sinus tachycardia, Macrocephaly, Moderate dilation of lateral ventricles

c.1258G > A

p.(Glu420Lys)

GDD, ID, Autism, Hypotonia, Tantrums, Perseverative behavior, Wide-based gait

Frontal bossing, Triangular face

Supernumerary nipple, Hypoplastic fifth toenails Astigmatism, Macrocephaly, White matter dysgenesis, Dysmorphic corpus callosum

c.589G > A

p.(Glu197Lys)

GDD, Moderate ID, Hypotonia, Non-verbal

Mild facial asymmetry

Congenital scoliosis, Difficulty chewing, Macrocephaly

Loveday et al. (2015)

c.592G > A

p.(Glu198Lys)

ID

Hypospadias, Increased height, macrocephaly

c.598G > A

p.(Glu200Lys)

ID

Increased height, macrocephaly

c.598G > A

p.(Glu200Lys)

ID, Parkinsonism

Increased height, macrocephaly

Houge et al. (2015)

c.157C > T

p.(Pro53Ser)

Severe ID, Non-verbal

Cataract

c.592G > A

p.(Glu198Lys)

Severe ID, Hypotonia, Ataxia

Pseudo-hydrocephalus, macrocephaly

c.592G > A

p.(Glu198Lys)

Severe ID, Hypotonia, Non-verbal, Ataxia

NA

c.592G > A

p.(Glu198Lys)

Severe ID, Hypotonia

Narrow palate

Increased weight, Fatigue, Hypoglycemia, Abnormal fat oxidation, Bilateral 6^th nerve palsy, Hydrocephalus, macrocephaly

c.592G > A

p.(Glu198Lys)

Severe ID, Epilepsy, Hypotonia, Non-verbal

Mild syndactyly, Mild ventricular dilatation

c.592G > A

p.(Glu198Lys)

Severe ID, Epilepsy, Hypotonia, Non-verbal, Ataxia

Increased weight, Scoliosis, Mild ventricular dilatation, Small corpus callosum, macrocephaly

c.592G > A

p.(Glu198Lys)

Severe ID, Hypotonia, Non-verbal

Increased height macrocephaly

c.598G > A

p.(Glu200Lys)

Mild ID, Hypotonia

Increased weight, Fatigue, Ptosis macrocephaly

c.598G > A

p.(Glu200Lys)

Mild ID, Hypotonia, Ataxia

Fatigue, Strabismus macrocephaly

c.602C > G p.(Pro201Arg)

Moderate ID, Epilepsy, Hypotonia, Ataxia

Hip dysplasia, Gastric reflux

c.619 T > A p.(Trp207Arg)

Moderate ID, Hypotonia

Scoliosis, Hip dysplasia, Fatigue, Mild mitochondrial dysplasia, Macrocephaly