A family with PTEN mutations with malignancy and an unusually high number of offspring with autism spectrum disorder: a case report

Abstract

BackgroundCowden’s syndrome (OMIM:158350), a rare genetic disorder (incidence ~ 1:250,000), is caused by mutations of the tumor suppressor gene PTEN. In this report, we describe clinical manifestations of a 56-year-old patient diagnosed with Cowden’s syndrome and his family with PTEN mutations. The family has an unusually high number of offspring with autism spectrum disorder.Case presentationExcept for his 80-year-old Caucasian father, all of our index case’s living Caucasian kindred (three children, brother, and nephew) had PTEN mutations and macrocephaly. Prior to genetic testing, his mother and sister died of breast cancer at 42 and 38 years old, respectively. After PTEN mutation was identified, our patient underwent complete thyroidectomy (histology showing micropapillary carcinoma) and right nephrectomy for renal cell carcinoma. All of his three children (13-year-old son, 11- and 8-year-old daughters) have been diagnosed with autism spectrum disorder. His son and brother underwent total thyroidectomy. His nephew had thyroid nodules. Management of Cowden’s syndrome requires clinical examinations and investigations every 6 to 12 months from 18 years old or 5 years before the family’s earliest age of cancer diagnosis and should focus on all clinical manifestations associated with PTEN mutations to identify early abnormal changes in skin, breasts, thyroid, endometrium, gut, and kidneys. Input from specialists across different disciplines is necessary.ConclusionsWe describe a man and his family with PTEN mutations who have increased risk of cancers and an unusually high number of offspring with autism spectrum disorder. Early recognition and close surveillance are vital in order to provide treatment and early screening for asymptomatic at-risk relatives.

Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome

“…Demographic information, including age (mean of 41.8 y) and sex distribution (male/female ratio 0.8), from our cohort, was similar to that in the literature (49.3 y, male/female ratio 1.1) 5–7,9,15–18 . In addition, the mean tumor size in our cohort (4.4 cm) was consistent with that previously reported (4.5 cm) 5–7,9,15–18 . The majority of PTHS-associated RCCs in our cohort demonstrated a favorable clinical behavior, again as reported by others.…”

“…RCC became recognized as part of the neoplastic spectrum of PHTS in 2000, relatively later than other known component malignancies such as breast, nonmedullary thyroid, and endometrial cancers 14 . Since 2012, several case reports and few case series have described PHTS-associated renal neoplasia 5–7,9,15–18 . Compared with the general population, RCC is 20- to 30-fold more common in PHTS, with a lifetime penetrance of ∼15% to 35% 5,19 Table 3.…”

“…14 Since 2012, several case reports and few case series have described PHTS-associated renal neoplasia. [5][6][7]9,[15][16][17][18] Compared with the general population, RCC is 20-to 30-fold more common in PHTS, with a lifetime penetrance of ∼15% to 35%. 5,19 Demographic information, including age (mean of 41.8 y) and sex distribution (male/female ratio 0.8), from our cohort, was similar to that in the literature (49.3 y, male/female ratio 1.1).…”

¿Es posible salir del autismo? Los chicos son mejores que las flores (2009) y La parsimonia autista de Yoon Ji Hoo

“…Si bien la etiología es variable y los factores de riesgo son variados, su heredabilidad se explica por su carácter genético, afectando a gemelos (monocigóticos principalmente) con una herencia de 40 % a 90 % 16 . Así, diversas enfermedades genéticas como el síndrome de X frágil, síndrome de Rett, y la esclerosis tuberculosa se encuentra implicadas con el TEA (principalmente con las mutaciones de los genes tumores supresores como PTEN) 17 . Por ello es necesario identificar las diferencias entre TEA y el trastorno por déficit de atención 18 como suceden con Yoo Ji Hoo en el caso del objeto del estudio.…”

How we approach complex vascular anomalies and overgrowth syndromes

“…Other expected morbidities of VMs with or without OG include pain, 15 infection, 22 and thrombotic events. 23 Neurocognitive dysfunction and mental health issues may be features of VA-OGS, 15,[24][25][26][27] including autism spectrum, 28 especially in patients with macrocephaly. Patients are at life-long risk of complications, although how severity changes over time varies and is not well documented for all VA-OGS.…”