Table 2.

Disorders to Consider in the Differential Diagnosis of NFIA-Related Disorder

Differential
Disorder		Gene(s)MOIClinical Features of the Differential Disorder
Overlapping w/NFIA-related disorderDistinguishing from NFIA-related disorder
Sotos syndrome 1 NSD1 AD
  • Macrocephaly
  • Ventriculomegaly
  • DD
  • Brain malformations incl partial-to-complete agenesis of corpus callosum
  • No urinary tract defects
  • Sotos syndrome typically includes distinctive facial appearance & overgrowth.
Acquired macrocephaly w/impaired intellectual development (OMIM 618286) NFIB AD
  • Macrocephaly
  • DD
  • Minor dysmorphic features
  • Brain malformations incl dysgenesis of corpus callosum
  • Neurodevelopmental phenotypes
No urinary tract defects (in affected individuals reported to date)
Malan syndrome 2 (OMIM 614753) NFIX AD
  • Macrocephaly
  • Ventriculomegaly
  • DD
  • Brain malformations incl hypoplasia of corpus callosum
Individuals w/Malan syndrome generally have an overgrowth phenotype.
Joubert syndrome 9 CC2D2A AR
  • Ventriculomegaly w/seizures in some affected individuals
  • Agenesis of corpus callosum
  • Hydrocephalus
  • Renal disease
  • Typically more severe than NFIA-related disorder
  • Characteristic MRI findings ("molar tooth sign")
  • Eye abnormalities
Strømme syndrome CENPF AR
  • Hydrocephalus
  • Agenesis of corpus callosum
  • Renal abnormalities incl hydronephrosis
  • Typically more severe than NFIA-related disorder
  • Intestinal atresia
  • Ocular abnormalities
  • Microcephaly
  • Cardiac involvement

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance

1.

Because Sotos syndrome and Malan syndrome have overlapping features, Sotos syndrome is sometimes referred to as Sotos syndrome 1.

2.

Malan syndrome is also referred to as Sotos syndrome 2.

From: NFIA-Related Disorder

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