Table 2.

Disorders to Consider in the Differential Diagnosis of PPP2R5D-Related Neurodevelopmental Disorder

Differential Diagnosis DisorderGene(s)MOIClinical Features of Differential Diagnosis Disorder
Overlapping w/PPP2R5D-related NDDistinguishing from PPP2R5D-related ND
PTEN hamartoma tumor syndrome PTEN AD
  • Macrocephaly
  • Autism
  • DD
  • Hamartomatous overgrowths of multiple tissues
  • ↑ cancer predisposition
MTOR-related disorders
(e.g., Smith-Kingsmore syndrome; OMIM 616638)		 MTOR AD
  • Megalencephaly
  • ID
  • ASD
  • Hypotonia
  • Cortical brain malformations (polymicrogyria, focal cortical dysplasia)
  • Pigmentary abnormalities of the skin
Sotos syndrome NSD1 AD
  • Megalencephaly
  • ID
  • Somatic overgrowth
  • Characteristic facial features
  • Additional congenital anomalies (e.g., cardiac, skeletal)
Megalencephaly-capillary malformation syndrome
(see PIK3CA-Related Segmental Overgrowth)		 PIK3CA AD
  • ID
  • Autistic features
  • Seizures
  • Hypotonia
  • Megalencephaly
  • Vascular malformations
  • Somatic overgrowth (that can be focal)
  • Lymphatic abnormalities
  • Digital abnormalities (syndactyly, polydactyly)
  • Cortical brain malformations (incl polymicrogyria)
  • Hydrocephalus
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome PIK3R2
AKT3
CCND2 		AD
  • ID
  • Autistic features
  • Seizures
  • Hypotonia
  • Megalencephaly
  • Cortical brain malformations (incl polymicrogyria)
  • Hydrocephalus
  • Polydactyly
16p11.2 deletion syndrome See
footnote 1.		AD
  • ID
  • Autistic features
  • Seizures
  • Hypotonia
Obesity in adolescence & later in life
Kleefstra syndrome EHMT1 AD
  • ID
  • Hypotonia
  • Seizures
  • Autistic-like features

AD = autosomal dominant; ASD = autism spectrum disorder; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; ND = neurodevelopmental disorder

1.

The 16p11.2 recurrent deletion involves the loss of one chromosome segment harboring 25 annotated genes or transcripts [Kumar et al 2008, Marshall et al 2008, Weiss et al 2008]. The recurrent deletion is flanked by segmental duplications that contain four additional genes.

From: PPP2R5D-Related Neurodevelopmental Disorder

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