Familial Intracranial Hypertension in 2 Brothers With PTEN Mutation: Expansion of the Phenotypic Spectrum

Abstract

PTEN (Phosphatase and Tensin Homolog on chromosome TEN) encodes a vastly expressed tumor suppressor protein that antagonizes the PI3 K signaling pathway and alters the MTOR pathway. Mutations in PTEN have been described in association with a number of syndromes including PTEN hamartoma-tumor syndrome, macrocephaly/autism, and juvenile polyposis of infancy. Although there is a wide variability in the clinical and radiologic presentations of PTEN-related phenotypes, the most consistent features include macrocephaly and increased tumorigenesis. Intracranial hypertension may be idiopathic or secondary to multiple etiologies. We describe 2 siblings harboring a PTEN mutation who presented with macrocephaly and intracranial hypertension. Repeat brain MRIs were normal in both. Acetazolamide treatment normalized intracranial pressure, but several trials of medication tapering led to recurrence of intracranial hypertension symptoms. The clinical presentation of our patients expands the PTEN-related phenotypes. We discuss the possible pathophysiology in view of PTEN function.

Diagnosis of idiopathic intracranial hypertension - the importance of excluding secondary causes: A systematic review

“…We found 42 articles with 105 cases: 48 pediatric and 57 adult (71–112), Table 4. The distribution was as follows: hematological diseases (N = 16) (90–93,95–104,106,107), rheumatologic diseases (N = 7): Behçet’s disease and systemic lupus erythematosus (SLE) (71,72,83,94,105,108,109), different genetic diseases (N = 5) (73,74,…”

“…The most common diseases in this group were anemia (N = 42), leukemia (N = 17) (75–77), Behçet’s disease (N = 7) SLE (N = 7) (94,105,108,109), head trauma (N = 7) (78,79), obstructive sleep apnea syndrome (N = 5) (80,81) and sickle cell disease (N = 5) (104,106). Cases related to sIH induced by genetic diseases were distributed as following: cystic fibrosis (N = 2), Gitelman’s syndrome (N = 1), Phosphatase and Tensin Homolog on chromosome TEN (PTEN)mutation (N = 1) Turner syndrome (N = 1) (73,74,110–112).…”

“…(78,79), obstructive sleep apnea syndrome (N ¼ 5) (80,81) and sickle cell disease (N ¼ 5) (104,106). Cases related to sIH induced by genetic diseases were distributed as following: cystic fibrosis (N ¼ 2), Gitelman's syndrome (N ¼ 1), Phosphatase and Tensin Homolog on chromosome TEN (PTEN) mutation (N ¼ 1) Turner syndrome (N ¼ 1) (73,74,(110)(111)(112).…”

Dual impact of PTEN mutation on CSF dynamics and cortical networks via the dysregulation of neural precursors and their interneuron descendants

“…Notably, the frequency of ChP hyperplasia (see Fig. 4A-C above) and ChP inflammation is increased in ASD patients 23,[82][83][84][85] , including those with PTEN-mutant autism, macrocephaly, and acetazolamide-sensitive intracranial hypertension 86 . Nkx2.1 + -Cre-dependent tdTomato reporter expression was not detected in the ChP of Pten cKO mice (Suppl.…”

“…Other PTEN-mutant patients with ASD or other NDDs have communicating ventriculomegaly and do not require CSF diversion to survive 81 . An increased frequency of ventriculomegaly has been reported in ASD patients 23,[82][83][84][85] , including patients with PTENmutant ASD and macrocephaly 86 . In a cohort of 920 patients with ASD and 1003 age-and sex-matched controls from the Autism Brain Imaging Data Exchange (ABIDE) collection 87,88 , we first corroborated the association of ventriculomegaly with ASD using the convolutional neural network SynthSeg+ to automatically segment subjects' brain MRIs 89 .…”