Country (Year) [Ref] | Age | Sex | Chief complaintsa | Major criteriab | Minor criteriac | History and other clinical manifestationsd | Diagnostic measurese | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
USA (2012) [38] | 42 | M | Rectal bleeding | Mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | Colon cancer Lipomas | Family history: Negative | Colonoscopy, genetic test, histology | ||||
Surgical history: Colectomy | |||||||||||
Medical observations: Colonic ganglioneuromatous polyps, mucocutaneous features | |||||||||||
Laboratory results & detailed informationf: Colonoscopy & microscopic examination: ganglioneuromatous polyposis, specimen contained an adenomatous polyp in addition to multiple, finger-like polyps and mesenteric lipomas; Genetic test: pathologic non-sense mutation at the PTEN locus | |||||||||||
Spain (2016) [2] | 57 | F | Dysphagia & recurrent endometrial carcinoma | Breast carcinoma, mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | Thyroid lesions | Family history: NA | Brain and chest CT, MRI of spine, genetic test | ||||
Surgical history: Thyroidectomy, hysterectomy | |||||||||||
Medical observations: Uterine leiomyomas, rectal bleeding secondary, anal polyp, sphenoid wing meningioma, meningiomas, thin-walled lung cyst, thoracolumbar scoliosis | |||||||||||
Laboratory results & detailed information CT: left sphenoid wing meningioma with extra-conal extension and resultant left optic nerve impingement and proptosis; right breast lesions MRI: thoracolumbar scoliosis with spondylosis and multilevel disc disease; Genetic test: pathogenic variants in the PTEN gene: (c.697C > T) (pArg233*) | |||||||||||
Tunisia (2012) [6] | 30 | F | Altered bowel habits | Macrocephaly, thyroid carcinoma, mucocutaneous lesions, acral keratosis | FDB, thyroid lesion, gastrointestinal hamartomas | Family history: Negative | Endoscopy, colonoscopy, breast US | ||||
Surgical observations: Surgical excision of breast nodules & thyroidectomy | |||||||||||
Medical observations: Congenital mental retardation. breast nodules, multiple gastrointestinal polyps, high-arched palate, adenoid facies, kyphoscoliosis and pectus excavatum, iron deficiency anemia | |||||||||||
Laboratory result & detailed information Breast US: bilateral nodules compatible with fibrocystic disease; Endoscopy: esophageal, duodenal, and gastric sessile polyps; Colonoscopy: multiple lesions in the sigmoid and rectum | |||||||||||
USA (2013) [14] | 14 | F | Menorrhagia refractory to intravenous estrogen | Endometrial carcinoma, Macrocephaly, mucocutaneous lesions, oral papules, trichilemmoma | Lipomas, fibroma | Family history: Hashimoto’s thyroiditis in two sisters, thyroid cancer in her father, goiter & fibrocystic breast disease in her mother | Endometrial curettage & pathological examination, PET/MRI of ovaries, colonoscopy, genetic test | ||||
Surgical history: Hysterectomy and laparoscopic excision of ovary at age 19 years | |||||||||||
Medical observations: Macrocephaly, endometriosis adenocarcinoma, colon polyps, gum fibroids, benign squamous cyst of right ovary | |||||||||||
Laboratory result & detailed information Endometrial curettage & Pathological examination: focal grade 1 endometriosis adenocarcinoma; PET/MRI: concerning for significant myometrium invasion, showed no involvement of the ovaries at age 14; Colonoscopy: multiple polyposis lesions in transverse and sigmoid colon; Genetic test: Arg335X (1003C > T) mutation in the PTEN gene | |||||||||||
Brazil (2015) [13] | 36 | F | Gingival growth | Macrocephaly, thyroid carcinoma, mucocutaneous lesions, oral papules | NA | Family history: NA | Histopathologic evaluation | ||||
Surgical history: Thyroidectomy, removing papules from hand & stomach | |||||||||||
Medical observations: Thyroid carcinoma, macrocephaly, Hashimoto thyroiditis & gastritis, arthrosis & fibromyalgia, depression, breast nodules, Heck’s disease, ductal ectasia | |||||||||||
Laboratory result & detailed information histopathologic evaluation: epithelial hyperplasia as a histological finding of biopsy from the gingival nodule | |||||||||||
Croatia (2019) [18] | 39 | F | White spot on gingiva, face, & hand | Thyroid carcinoma (follicular), mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | FDB, Lipoma, Fibroma, Vascular anomalies | Family history: Endometrial polyp in mother & thyroid cancer in sister | Gynecological US, cardiological examination | ||||
Surgical history: Surgery of thyroid, cavernous ovary lymphangioma and leiomyomas of uterus | |||||||||||
Medical observations: Fibrocystic changes breast papillomatosis, liver hemangioma, lipoma, multiple fibromas, genitourinary tumours, endometrium polyp, myomas, thyroid abnormalities, pericardial effusion | |||||||||||
Laboratory result & detailed information Gynecological US: polyp in the endometrium and multiple myomas of the myometrium; Cardiological examination: pericardial effusion | |||||||||||
USA (2017) [39] | 63 | M | Lesions on calf,abdomen, clavicle & elbow | Thyroid carcinoma, mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | Thyroid lesion | Family history: Unremarkable | CT-scan of neck, IHC | ||||
Surgical history: Thyroidectomy, cholecystectomy | |||||||||||
Medical observations: Thyroid cancer, hypertension, obstructive sleep apnea, nodular lesions in right parotid gland, SLA, CCA | |||||||||||
Laboratory result & detailed information CT: Nodular lesions in the right parotid gland; IHC: Sebaceous lymph adenoma, Clear Cell Acanthoma, | |||||||||||
Czech (2011) [40] | 55 | F | Epileptic paroxysms | Macrocephaly, thyroid carcinoma, mucocutaneous lesions | Intellectual disability, Thyroid lesion, GI hamartomas | Family history: colon cancer in mother | Endoscopy, brain CT, IHC, genetic test | ||||
Surgical history: thyroidectomy, hysterectomy, adnexectomy and abdominoperineal surgery | |||||||||||
Medical observations: Gastric cancer, Myomatosis, Adenopapilocarcinoma of ovary, epileptic paroxysm, decline in cognitive functions & memory, polyps in stomach, duodenum & colon | |||||||||||
Laboratory result & detailed information Endoscopy: hundreds of polyps in the stomach, duodenum and colon; CT: frontal lesion; IHC: invasive follicular carcinoma benign meningioma; Genetic test: heterozygous deletion mutation at (c.438delT), exon 5 | |||||||||||
Japan (2020) [41] | 47 | F | Tumour in her right breast | Breast carcinoma, thyroid carcinoma, LDD | Thyroid lesions | Family history: Breast cancer in her mother and sister | Breast US, pathological examination, chest CT, chest & brain MRI | ||||
Surgical history: Mastectomy, thyroidectomy | |||||||||||
Medical observations: Thyroid carcinoma, breast carcinoma, LDD | |||||||||||
Laboratory result & detailed information Breast US: irregular marginated hypoechoic mass measuring 15.1 × 15 × 9.4 mm in the 12 o’clock region of the right breast; Pathological examination: ductal carcinoma in situ (DCIS) in the right mammary gland and invasive ductal carcinoma in the left mammary gland; Chest MRI: Primary tumour of the right mammary gland to be a mass 15 mm and early phase linear enhancement for the left side = > stage 0 (cTisN0M0) right breast cancer and stage IIA (cT2N0M0) for the left side; Brain MRI: alternative isointense and hyper intense bands in the left cerebellar hemisphere; Chest CT: no lymph node metastases or distant metastases | |||||||||||
Portugal (2020) [42] | 28 | F | NA | Macrocephaly, thyroid carcinoma, breast carcinoma, Mucocutaneous lesions: acral keratosis | Intellectual disability | Family history: thyroid carcinoma in her mother and aunt | Breast CT & IHC, thyroid & breast US, genetic test | ||||
Surgical history: mastectomy, thyroidectomy | |||||||||||
Medical observations: Hydrocephaly, severe microcytic & hypochromic anemia, macrocephaly, thyroid & breast cancer | |||||||||||
Laboratory result & detailed information Breast CT and IHC: breast lump, high metastatic breast sarcoma; Thyroid US: 5.6-cm hypoechogenic nodule and anecogenic areas fine-needle biopsy and was diagnosed with follicular lesion of undetermined significance (FLUS) (Bethesda category III); Genetic test: a change in heterozygote, pathogenic variant c.405dupA (p. (Cys136Metfs * 44) in the PTEN gene | |||||||||||
India (2015) [43] | 41 | F | Lesion on neck, axillae, forehead | Macrocephaly, mucocutaneous lesions, oral papules, acral keratosis | Thyroid lesions | Family history: NA | Ultrasound abdomen & pelvis, chest X-ray & ECG, brain MRI, GI endoscopy, colonoscopy, mammography | ||||
Surgical history: Thyroidectomy | |||||||||||
Medical observations: Syndactyly and polydactyly, cobblestone tongue with coalesced papules | |||||||||||
Laboratory result & detailed information Imaging studies (ultrasound abdomen and pelvis, chest x-ray, ECG, MRI brain and echocardiography) and upper GI endoscopy, colonoscopy and mammography were normal | |||||||||||
USA (2017) [44] | 64 | F | Painful gum & red painful palate | Breast carcinoma, mucocutaneous lesions, oral papules, acral keratosis | NA | Family history: NA | Extra & intra oral examination, IHC | ||||
Surgical history: NA | |||||||||||
Medical observations: Malignancy of GI tract, anemia, asthma, breast cancer | |||||||||||
Laboratory result & detailed information Intraoral examination: papules, pebbles on the case of the tongue and maxillary; IHC: Superficial keratinized squamous epithelium overlying a mass of dense fibrous connective tissue composed of interlacing bundles of collagen fibers interspersed by fibroblasts and blood vessels | |||||||||||
Japan (2014) [45] | 37 | M | Eyeball movement and gait disturbance | Mucocutaneous lesions, oral papules, acral keratosis | Intellectual disability, Vascular anomalies | Family history: CS in his mother with breast, thyroid & uterus cancers | Brain CT & MRI, DSA, IHC, genetic test | ||||
Surgical history: Intracranial surgery | |||||||||||
Medical observations: Hemiparesis, left facial & right abducens nerve palsy, right Horner syndrome | |||||||||||
Laboratory result & detailed information Brain CT & MRI: hematoma diameter 27 mm & circular area of heterogeneous intensity in the pons; DSA: no abnormal vessels & no tumour staining; IHC: dura mater contained abnormal vessels & ectatic cortical veins presented in the arachnoid space; Genetic test: PTEN mutation | |||||||||||
Italy (2018) [46] | 43 | M | Lesion localized on the gingiva | Breast carcinoma, thyroid carcinoma, mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | NA | Family history: Mother & sister suffered from CS and died from breast cancer | IHC, panoramic radiography | ||||
Surgical history: Mastectomy, thyroidectomy | |||||||||||
Medical observations: Breast & Thyroid carcinoma, periodontal disease | |||||||||||
Laboratory result & detailed information IHC: hyper plastic epidermoid covering and parakeratosis on the surface; Since the diagnosis of the disease had already been made, there was no information about the diagnostic methods | |||||||||||
Japan (2020) [47] | 31 | F | Abnormal genital bleeding | Breast carcinoma, Macrocephaly, Endometriosis carcinoma | NA | Family history: CS in mother | Pelvic US, abdominopelvic CT, IHC, genetic test | ||||
Surgical history: D&C, hysterectomy, salpingo-oophorectomy | |||||||||||
Medical observations: Obesity, mass in the left ovary, APAM of endometrium and ovarian metastasis | |||||||||||
Laboratory result & Detailed information: Pelvic US: thickening of the endometrium and a cystic mass in the left ovary; Abdominopelvic CT: endometrial thickening and a 5-cm cystic mass in the left adnexal region; IHC: grade 1 endometriosis carcinoma component presenting cribriform glands; Genetic test: Pathogenic variants of PTEN (c.C1003T, p.R335X) in both the patient and her mother | |||||||||||
Spain (2019) [48] | 52 | F | Multiple warts of hands & feet | Endometrial carcinoma, Mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | Thyroid lesions, Fibroma | Family history: Negative | GI endoscopy, genetic test | ||||
Surgical history: hysterectomy, thyroidectomy | |||||||||||
Medical observations: Bilateral cholesteatoma, trigeminal schwannoma, uterine fibroids, finger fibroma, tracheal fibrotic nodules, trichilemmoma, oral fibroma | |||||||||||
Laboratory result & Detailed information: GI endoscopy: glycogenic acanthosis and ten colorectal inflammatory and hyperplastic polyps; Genetic test:a heterozygous mutation = a four-nucleotide deletion (c.510_513del) resulting in a premature stop codon (p.Ser170Argfs*12) | |||||||||||
Lebanon (2017) [49] | 55 | F | Left axillary sentinel node | Breast carcinoma, Macrocephaly, Endometrial, carcinoma | Lipomas, Fibroma | Family history: Breast cancer in one of siblings | Axilla &Brain MRI, IHC, genetic test | ||||
Surgical history: Partial mastectomy | |||||||||||
Medical observations: Papillary sclerosing lesion, DCIS, gangliocytoma, neurofibroma meningioma, extracranial meningothelial proliferation | |||||||||||
Laboratory result & Detailed information: Axilla MRI: not demonstrate any suspicious lymph nodes; IHC: high grade ductal carcinoma in situ; Brian MRI: no lesions suggestive of meningioma; Genetic test: PTEN c.209 + 5G > A alteration confirming the clinical impression of CS | |||||||||||
Japan (2019) [15] | 39 | F | Lower abdominal pain & melena | Macrocephaly, Endometriosis carcinoma | Thyroid lesions, Lipoma, Fibroma, GI hamartomas | Family history: Breast cancer in mother and cutaneous papilloma in father | Colonoscopy, IHC, GI endoscopy, MRI of pelvic, CT, FDG-PET | ||||
Surgical history: Pelvic & para-aortic lymphadenectomy, hysterectomy, salpingo-oophorectomy, omentectomy | |||||||||||
Medical observations: Macrocephaly, breast fibroma, ovarian tumour, endometriosis cancer, colorectal polyposis lesions | |||||||||||
Laboratory result & Detailed information: Colonoscopy: colorectal polyposis lesions; IHC: hamartoma polyps and ectopic endometrial implants; GI endoscopy: multiple esophageal papillomas and glycogenic acanthosis; MRI: gluteal subcutaneous lipoma CT: heterogeneously enhanced mass, 9 cm; FDG-PET: abnormal uptake by the ovarian tumour (SUVmax: 8.33) | |||||||||||
Japan (2015) [50] | 75 | M | Hoarseness & dysphagia | Mucocutaneous lesions, oral papules | Thyroid lesions, Vascular anomalies | Family history: NA | MRI, histology & IHC, GI endoscopic, genetic test | ||||
Surgical history: NA | |||||||||||
Medical observations: Lung adenocarcinoma, cerebellar tumour, GI polyposis, pneumonia | |||||||||||
Laboratory result & Detailed information: MRI: cerebellar dysplastic gangliocytoma; IHC: lung adenocarcinoma (T4N2M1b, Stage IV); GI endoscopic: Gastrointestinal polyposis; Genetic test: PTEN gene mutation, a point mutation (TGT to CGT) at exon 5 in codon 136 was detected in his serum | |||||||||||
USA (2016) [51] | 51 | M | Jaundice & abdominal pain | Macrocephaly, thyroid carcinoma, mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | Lipomas, Thyroid lesions | Family history: Macrocephaly | Chest, abdomen & pelvis CT& PET-CT, pathological evaluation, IHC, Endoscopic sonography, genetic test | ||||
Surgical history: Thyroidectomy | |||||||||||
Medical observations: Macrocephaly, thyroid carcinoma, mucocutaneous, multiple intestinal polyps | |||||||||||
Laboratory result & Detailed information: CT: large (9 × 8 × 4 cm) ill-defined mass of the head and neck of the pancreas, invading the celiac axis; encasing the celiac artery, superior mesenteric, and splenic arteries and veins; and compressing the portal vein confluence; PET-CT: large central lesion in the abdomen; IHC& pathological evaluation: cytoplasmic staining of tumour cells, grade 1 NET with a Ki-67 < 2% and involved margins; Endoscopic sonography: stage uT4N1Mx determined Genetic test: nonsense mutation c.697C3T (p.R233*) causing a premature stop codon in exon 7 | |||||||||||
Japan (2018) [16] | 46 | M | Fresh blood in his stool & shortness of breath | Mucocutaneous lesions, oral papules, acral keratoses | GI hamartomas, Thyroid lesions, Fibroma, Vascular anomalies | Family history: Breast cancer in his mother | Neck US, GI endoscopy, pathophysiological examination, CT angiography | ||||
Surgical history: Gastrectomy | |||||||||||
Medical observations: Duodenal ulcer, anemia, adenomatous goiter, vascular anomalies | |||||||||||
Laboratory result & Detailed information: US: adenomatous goiter in the thyroid gland; GI endoscopy: numerous polyposis lesions; CT angiography: vascular malformation in the wall of the sigmoid colon; Pathological examination: vascular malformations expanded from the submucosal layer to the mesocolon | |||||||||||
USA (2019) [52] | 50 | M | Vomiting, vertigo and balance difficulties | LDD, Macrocephaly | Thyroid lesions | Family history: CS | Brain MRI, IHC | ||||
Surgical history: Thyroidectomy, right cerebellar LDD resection, Parathyroidectomy | |||||||||||
Medical observations: multinodular goiter; gangliocytoma, abducens cranial nerve palsy; altered mental status, Parathyroid adenoma | |||||||||||
Laboratory result & Detailed information: MRI: cerebellar tumour and progression of the left cerebellar gangliocytoma IHC: expansion of the cerebellar folia, with near complete replacement of the small neurons of the internal granular layers by larger, ganglionic neurons | |||||||||||
USA (2016) [53] | 26 | F | Painful perianal lesion | Macrocephaly, Mucocutaneous lesions, trichilemmoma | Thyroid lesion, Lipoma, Colon cancer | Family history: NA | Histopathologic examination, IHC, breast US | ||||
Surgical history: hemicolectomy, Subtotal colectomy, Breast lumpectomy | |||||||||||
Medical observations: Ganglioneuromas, focal intramucosal adenocarcinoma of the colon, proliferative glandular lesion, breast lesions | |||||||||||
Laboratory result & Detailed information: Histopathological examination: a circumscribed, lobulated, proliferative glandular lesion with areas of expanded fibromyxoid stroma and epithelial hyperplasia with apocrine and columnar cell changes, arranged in a papillary, micropapillary and cribriform architecture; IHC: loss of PTEN expression in the epithelial component of the lesion. | |||||||||||
USA (2020) [54] | 35 | F | Forgetfulness and fatigue | LDD | NA | Family history: NA | Cerebral MRI, IHC | ||||
Surgical history: Craniotomy for resection of meningioma, stereotactic radiosurgery | |||||||||||
Medical observations: Meningiomas, dysplastic gangliocytoma | |||||||||||
Laboratory result & Detailed information: MRI: lesion in the cerebellum suggesting dysplastic gangliocytoma; IHC: EMA and vimentin, consistent with World Health Organization (WHO) grade I meningioma margin. The patient had already been diagnosed with the CS | |||||||||||
Italy (2012) [55] | 14 | M | Epileptic seizures | Macrocephaly, Mucocutaneous lesions, oral papules, acral keratosis | Autism, Intellectual disability | Family history: Macrocephaly, dysthyroidism, GI cancers, autism, and behavioral and psychiatric disorders | Cerebral MRI, ECG, IHC, genetic test, laboratory test | ||||
Surgical history: Nephrectomy | |||||||||||
Medical observations: Autism, macrocephaly | |||||||||||
Laboratory result & Detailed information MRI: right periventricular hyperintensity probably due to a remote hypoxic-ischemic insult; ECG: focal spike-wave complexes over the left temporal regions. IHC: focal prominent epidermal hyperplasia that at its periphery is demarcated by elongated rete ridges; Genetic test: an exon 2 deletion was detected; Laboratory test: moderate increase of thyrotrophin-stimulating hormone and free triiodothyronine and uncertain values for anti-endomysial antibodies with positivity for human leukocyte antigen (HLA) haplotypes (HLADQ2 and HLA-DQ8) associated with celiac disease | |||||||||||
USA (2018) [56] | 57 | F | Progressive weakness &urinary incontinence | Breast carcinoma, Macrocephaly | RCC, Lipomas, Vascular anomalies | Family history: Positive of cancers | MRI, spinal angiography, genetic test | ||||
Surgical history: Nephrectomy | |||||||||||
Medical observations: DCIS, multiple malignancies, squamous cell carcinoma of scalp, diabetes, multiple benign colon polyps, longitudinally extensive myelopathy, epidural lesions with bony erosion, thoracolumbar spinal cord lesion | |||||||||||
Laboratory result & Detailed information MRI: longitudinally extensive myelopathy; Spinal angiography: 2 SEAVFs; Genetic test: A deleterious mutation (209 + 4_209 + 7delAGTA) was found in intron 3 of the PTEN | |||||||||||
Korea (2021) [57] | 23 | F | NA | Endometrial carcinoma, Mucocutaneous lesions | Thyroid lesion, Vascular anomalies | Family history: NA | Colonoscopy, endoscopy, genetic test | ||||
Surgical history: Bariatric salpingectomy, Surgery for congenital vascular malformation of the leg, surgery for atypical ductal hyperplasia in the left breast & intraductal papilloma in the right breast, thyroid lobectomy & right central neck dissection pelvic lymph node dissection, left thyroidectomy, total hysterectomy, laparoscopic sleeve gastrectomy | |||||||||||
Medical observations: Obesity & diabetes; before and after surgery, changes in HOMA-IR and HOMA-B; Cystic lesion in thyroid gland, multiple colon polyps, small bowel polyps, metastatic papillary thyroid cancer to the lung | |||||||||||
Laboratory result & Detailed information Colonoscopy: multiple colon polyps (biopsy: lymphoidpolyps) were detected; Capsule endoscopy: scattered small bowel polyps; Genetic test: variant in which cytosine, the 289th base of the PTEN gene, was changed to thymine (c.289C > T). Consequently, glutamine, the 97th amino acid, was replaced with a stop codon (p.Gln97*) | |||||||||||
Italy (2014) [58] | 26 | M | asymptomatic keratotic lesions of the maxillary & mandibular gingiva | Mucocutaneous lesions, oral papules, acral keratosis | Fibroma | Family history: NA | Laboratory tests, IHC, GI endoscopy, genetic test | ||||
Surgical history: NA | |||||||||||
Medical observations: celiac disease, papillomatous lesions of the penis, hands & plantar skin, gastric polyposis lesions | |||||||||||
Laboratory result & Detailed information Hematology and chemistry: hematologic tests, including BS, Na, K, Ca, AST, ALP, LDH, Cr, HCT, RBC, HB, MCV, Plt, WBC, HIV, hepatitis B, C; All Laboratory test values were normal; IHC: proliferation of multiple benign fibromas with overlying hyperkeratosis; GI endoscopy: gastric polyposis lesions; Genetic test: germline mutation in exon 8 | |||||||||||
Brazil (2012) [59] | 24 | F | asymptomatic lesions in the oral cavity | Macrocephaly, Mucocutaneous lesions, oral papules | Thyroid lesion | Family history: ovarian & breast cancer in her mother | Histopathologic evaluation, endoscopy, Skull x-ray | ||||
Surgical history: thyroidectomy | |||||||||||
Medical observations: chronic urticaria with symptomatic dermographism, delayed motor and psychiatric development, hypotonia, macrocephaly, pectus excavatum, scoliosis, dolichocephaly and adenoid facies; polyposis in the GI tract, nodularhyperplasia of the thyroid | |||||||||||
Laboratory result & Detailed information Hematology and chemistry; including Ca, ALP and AST and urinalysis were normal; Histopathologic analysis: nodular hyperplasia of the thyroid; Endoscopy: polyposis in the GI tract | |||||||||||
Japan (2018) [60] | 36 | M | Facial seizure during sleep | Macrocephaly, Mucocutaneous lesions, oral papules | NA | Family history: hepatocellular carcinoma in his father | Brain MRI, CT-scan GI endoscopy, genetic test, PCR | ||||
Surgical history: NA | |||||||||||
Medical observations: Macrocephaly, facial seizure | |||||||||||
Laboratory result & Detailed information Blood tests: for autoantibodies, amino acids, lactate, pyruvate, pituitary hormone, tumour markers, and infectious agents showed no abnormalities; Brain MRI: focal cortical dysplasia; CT: hypometabolism of cortical dysplasia; GI endoscopy: multiple polyps Genetic test: heterozygous deletion in exon 5 (c.486delC) | |||||||||||
Portugal (2016) [61] | 36 | F | Headache & visual blurring bilaterally | Thyroid cancer, mucocutaneous lesions, acral keratosis, LDD | NA | Family history: breast carcinoma in her mother & sister | CT, MRI, OCT, genetic test | ||||
Surgical history: thyroidectomy | |||||||||||
Medical observations: FDB | |||||||||||
Laboratory result & Detailed information CT: unilateral cerebellar mass in the right hemisphere; MRI: right cerebellar mass with secondary hypertrophy of the cerebellar folia with a striated or tigroid pattern characteristic of LDD; OCT: thickening of peripapillary retinal nerve fiber layer; FA: leakage from the optic discs and confirmed papilledema; Genetic test: PTEN mutation c.493G > T | |||||||||||
USA (2018) [62] | 32 | F | Osteosarcoma and its screening process | NA | FDB | Family history: Bladder cancer in her maternal grandfather, ovarian cancer in her maternal grandmother; brain, breast, colon, thyroid cancer in her mother; a soft-tissue mass in her brother | Genetic test, colonoscopy, endoscopy | ||||
Surgical history: Surgery for osteosarcoma of femur, prophylactic bilateral mastectomy | |||||||||||
Medical observations: Osteosarcoma of her left femur, right benign breast mass | |||||||||||
Laboratory result & Detailed information Genetic test: non-synonymous c.17_18delAA frameshift mutation in exon 1 of PTEN and a c.116G > T (p.R39L) missense mutation of serine/threonine kinase 11(STK11) of unknown significance; Colonoscopy & Pathological examination: 75–100 polyp and ganglioneuromas in splenic flexure, descending and sigmoid colon | |||||||||||
Portugal (2017) [63] | 53 | M | Fibromas on the trunk and hyperkeratotic lesions on the hands | Mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma, thyroid carcinoma, penile melanosis, macrocephaly | Fibroma, Lipomas, GI hamartomas | Family history: Negative | Genetic test, laboratory tests | ||||
Surgical history: Thyroidectomy | |||||||||||
Medical observations: Malignant thyroid disease, intestinal polyposis, papillomatosis of the oral cavity | |||||||||||
Laboratory result & Detailed information Genetic test: PTEN mutation; Laboratory test & renal ultrasound: no significant changes | |||||||||||
Japan (2018) [64] | 65 | F | Lesions on skin | Thyroid carcinoma, mucocutaneous lesions, oral papules, acral keratoses | FDB, Vascular anomalies | Family history: NA | Mammography, genetic test, Ileocolonoscopy | ||||
Surgical history: | |||||||||||
Medical observations: Malignant thyroid disease, Intestinal polyps, oral cavity papillomatosis | |||||||||||
Laboratory result & Detailed information Mammography: carcinoma of the left breast; Genetic test: a heterozygous c.1003C > T (p.R335X) mutation of the phosphatase and tensing homolog (PTEN) gene; Ileocolonoscopy: hemispherical or drumstick-shaped multiple polyps in the terminal ileum | |||||||||||
USA (2020) [65] | 56 | F | Diplopia Headaches | LDD | RCC | Family history: NA | MRI | ||||
Surgical history: NA | |||||||||||
Medical observations: Hashimoto’s thyroiditis, RCC | |||||||||||
Laboratory result & Detailed information MRI: non-enhancing cerebellar lesion, the patient was previously diagnosed with CD and we can exclude it | |||||||||||
USA (2015) [66] | 31 | M | Lump in his right breast | Macrocephaly, Breast carcinoma | Thyroid lesion | Family history: Hodgkin lymphoma in great grandparent, leukemia in his aunt, breast cancer and penis cancer in great grandparents | Chest CT, thyroid US, abdominal CT, genetic test | ||||
Surgical history: Bilateral mastectomies | |||||||||||
Medical observations: lymphadenopathy | |||||||||||
Laboratory result & Detailed information Chest CT: mediastinal mass; Genetic test: heterozygous missense variant (c.103A > G; p.Met35Val) was observed in the PTEN gene; Thyroid US: multiple nodules; Colonoscopy: sessile polyps | |||||||||||
Singapore (2021) [67] | 48 | F | Headache and dizziness | Breast carcinoma, LDD | GI hamartoma | Family history: | Brain CT, MRI, IHC | ||||
Surgical history: resection of the tumor of brain | |||||||||||
Medical observations: hemangioma, breast cancer, hamartomatous polyps | |||||||||||
Laboratory result & Detailed information Brain CT: large hypodense lesion at the right cerebellum with resulting hydrocephalus; MRI: tiger-striped pattern of cerebellar folia in the right cerebellum; IHC: ganglion cells were positive for synaptophysin and neurofilament | |||||||||||
Korea (2012) [68] | 29 | F | Dyspepsia | Mucocutaneous lesions, oral papules, acral keratosis, trichilemmomas, thyroid carcinoma | GI hamartoma Thyroid lesion | Family history: | EGD, colonoscopy, genetic test | ||||
Surgical history: left lobectomy | |||||||||||
Medical observations: | |||||||||||
Laboratory result & Detailed information EGD: gastric, duodenal polyps and esophageal acanthosis; colonoscopy: hamartomatous polyps in the rectum and oral mucosal papillomatosis Genetic test: heterozygous transition of C to A at nucleotide 633 in exon 6 (NM_000314.4 c.633C > A), which is a nonsense mutation, making a stop codon (p.Cys211*) | |||||||||||
Iran (2010) [19] | 16 | F | Subtle signs of CS | Mucocutaneous lesions, acral keratosis, trichilemmomas | FDB | Family history: NA | PCR-SSCP, HMA, genetic test | ||||
Surgical history: Mastectomy | |||||||||||
Medical observations: FDB | |||||||||||
Laboratory result & Detailed information PCR-SSCP: all identified mutations were present in exon 5; HMA: heteroduplex bands with mobility shifts in lanes 2,5&6 are mutant samples Genetic test: nucleic acid alteration = c.341 T > G | |||||||||||
UK (2015) [17] | 48 | M | Dysphagia Right hearing loss and facial weakness | LDD | Thyroid lesion | Family history: LDD in his nephew | IHC, MRI, CT-scan | ||||
Surgical history: brain& neck resection mass | |||||||||||
Medical observations: nasal polyps, high-grade neoplasm involving the facial nerve, deafness | |||||||||||
Laboratory result & Detailed information IHC: for neurofilament protein showed residual nerve fibers infiltrated by the tumour; MRI and CT: brain and neck showed a mass (4.2*2.9 cm) at the cerebellopontine angle; Genetic test: Nucleic acid alteration = c.1003C > T, amino acid alteration = p.(Arg335Ter), the genetic testing of the proband’s offspring identified the same mutation | |||||||||||
Italy (2021) [69] | 46 | M | Abdominal pain | Mucocutaneous lesions, oral papules, acral keratoses, macrocephaly | GI hamartoma | Family history: Colon and breast cancer in his mother | Colonoscopy, IHC, EGD, genetic test | ||||
Surgical history: NA | |||||||||||
Medical observations: Macrocephaly; polypoid lesions in GI | |||||||||||
38 | F | Abdominal pain | Thyroid carcinoma, mucocutaneous lesions, oral papules, acral keratosis, trichilemmoma | FDB, Fibroma | Family history: Negative | Endoscopy, colonoscopy, IHC, EGD, uterus US, genetic test | |||||
Surgical history: Thyroidectomy & mastectomy | |||||||||||
Medical observations: Thyroid carcinoma, FDB with lobular carcinoma in situ, uterine fibroids and squamous polyp of uterine cervix | |||||||||||
Laboratory result & detailed information Case 1 (M). colonoscopy: more than 20 sessile and pedunculated polyposis lesions throughout the entire colon and the terminal ileum; IHC: large cistically dilated tortuous intestinal glands surrounded by stroma; EGD: multiple small carpeting lesions; Genetic test: heterozygous variant c.306del, p.Lys102Asnfs*11 (NM_000314.8) was detected in the exon 5 of the PTEN gene Case 2 (F): Endoscopy: Gastrointestinal polyposis lesions; Colonoscopy: more than 20 sessile polyps involving the entire colon; IHC: simultaneous presence of enlarged lymphoid follicles and hyperplastic polyps; EGD: numerous millimetric sessile lesions covering all the esophageal mucosa and gastric mucosa; Genetic test: heterozygous variant c.253 + 1G > A; p.? (NM_000314.8) (rs587776667) | |||||||||||
Iran (2022) [This study] | 39 | F | Rectorrhagia refractory dyspepsia | Breast carcinoma | Thyroid lesion | Family history: Gastric cancer in her father & breast cancer in her cousin | Endoscopy, colonoscopy, laboratory test, genetic test, breast UC, histopathological examination, endometrial biopsy, abdominal CT scan, thyroid sonography | ||||
Surgical history: Partial mastectomy | |||||||||||
Medical observations: Polyps in stomach, duodenum, rectosigmoid | |||||||||||
Laboratory result & Detailed information Hematology: WBC = 2.2 × 103/ μL, RBC = 4.141 × 106/ μL, HGB = 9.2 g/dl, PLT = 443 × 103/ μL; Chemistry:T3, T4, and TSH were within thenormal limits; Genetic test: RefSeq = NM_00314.7, Nucleic acid alteration = c.697C > T, Amino acid alteration = (p.Arg233Ter) rs121909219, Zigosity = Heterozygous, Ch. Location = Chr10 Mutation: Pathogenic |