Familial Adenomatous Polyposis (FAP) is a multi-tumoral syndrome that includes neoplasms in the duodenum, brain, pancreas and thyroid. The Cribriform Morular Variant (CMV) is a rare form of Papillary Thyroid Cancer seen in patients with FAP. Presented here is a 32 year old female who initially presented with an anterior neck mass followed years later by a rectal mass. She was diagnosed with FAP and colorectal adenocarcinoma and underwent total proctocolectomy with end ileostomy. She subsequently underwent a total thyroidectomy which revealed CMV Papillary Thyroid Carcinoma (CMV-PTC). Since FAP can have diverse presentations, a high index of suspicion is needed in order to make an earlier diagnosis to reduce potential morbidity and mortality. Papillary thyroid carcinoma can predate colonic polyposis. Identifying CMV-PTC early on can serve as an opportunity diagnose FAP early.

Hailey-Hailey Disease (HHD) is a rare, chronic skin condition characterized by relapsing episodes and spontaneous remissions, significantly affecting patients’ quality of life, especially in severe cases. Due to its rarity, there are no established evidence-based treatment guidelines or extensive clinical trials. This case report highlights the rapid improvement of HHD in a 55-year-old Filipino woman treated with a combination of 5-fluorouracil and excimer phototherapy, suggesting that this treatment approach may be an effective alternative for managing the disease.

Multiple Familial Trichoepithelioma (MFT) is a subtype of trichoepithelioma that begins during childhood as asymptomatic skin colored nodules predominantly on the central area of the face. It is a rare benign tumor of follicular differentiation associated with syndromic disorders and with mutations on the following genes: PTCH, 9p21 and CYLD. Overlap features between trichoepitheliomas and basal cell carcinomas may be present clinically and histopathologically. Hence, the importance of clinicopathologic differentiation between both as treatment options and prognosis varies.

We have a 52 year old male who presented with multiple asymptomatic, coalescent, flesh colored papules and nodules on the face and on the bilateral ears that started during childhood with gradual progression in size. Dermoscopy revealed thin arborizing vessels, milia-like cysts on a whitish background. History of similar lesions are noted among eight of his family members. Skin biopsies were taken on two nodules which showed tumor islands of basaloid cells with peripheral palisading, surrounded by fibrous stroma, characteristic papillary mesenchymal bodies and presence of keratin filled cysts. Genetic testing was advised and the planned course of action for the patient is to undergo ablative carbon dioxide laser combined with topical imiquimod cream to minimize recurrence.

This case highlights the relevance of multiple biopsy sites to rule out other differential diagnoses presenting with leonine facies and syndromic disorders associated with multiple familial trichoepitheliomas. Genetic testing is recommended but presumptive diagnosis may be made through positive family history, clinical and histopathologic features.

: Cerebral cavernous malformation (CCM) is a type of vascular malformations characterized by the absence of intervening brain parenchyma. Cerebral cavernous malformations are of two forms, sporadic and familial. About 0.4-0.8% of the population are affected as assessed based on Magnetic Resonance Imaging (MRI) findings and postmortem findings. Three genetic mutations have been identified: CCM1, CCM2, CCM3, with an incidence of 40%, 40% and 20%, respectively. : This study presents five members diagnosed with Familial CCM in a Filipino family. A 25-year-old male, from a low socio-economic background, was admitted due to a progressive generalized headache of 2 years’ duration, during which multiple brain lesions were observed on MRI. All members of the family became symptomatic before 30 years of age, and four out of the five members underwent surgery. However, molecular genetic testing was not performed as the patient could not afford it. The testing was not covered by the country’s insurance system, and it would have been an out-of-pocket expense. In patients diagnosed with cerebral cavernous malformations, a thorough clinical and family history is warranted accompanied by MRI-GRE (Magnetic Resonance Imaging Gradient Echo) and MRI T2 help establish final diagnosis. Confirmation with molecular genetic testing should be offered to all members of the family for proper neurological and genetic care.
Human ; Male,Female ; Adult: 25-44 yrs old ; Middle Aged: 45-64 yrs old ; Aged: 65-79 yrs old ; familial cerebral cavernous malformation

OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (r_s=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (r_s=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.
Child ; Humans ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors ; Familial Hypophosphatemic Rickets/diagnosis* ; Rickets, Hypophosphatemic/diagnosis*

A 15-year-old, Indian, female child of a second-degree consanguineous marriage, presented with polymorphic yellowish-brown nodular cutaneous lesions over the dorsal aspect of both elbows, knees (Figure 1A) and buttocks (Figure 1B). These were suggestive of xanthoma tuberosum and were first noted at 4 years old. There were no spots over the eyelids, acanthosis, skin tags or tendon xanthomas. Arcus juvenilis was not noted. A bilateral carotid bruit was appreciated.
xanthoma ; familial ; hypercholesterolemia ; LDL

Humans ; Pulmonary Arterial Hypertension ; Bone Morphogenetic Protein Receptors, Type II/metabolism* ; Pedigree ; Mutation ; Familial Primary Pulmonary Hypertension

Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.
Child ; Infant, Newborn ; Female ; Humans ; Cholesterol, LDL/therapeutic use* ; Liver Transplantation ; Homozygous Familial Hypercholesterolemia ; Retrospective Studies ; Hyperlipoproteinemia Type II/surgery* ; Lipids ; Hypolipidemic Agents/therapeutic use*

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg^-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Mice ; Male ; Female ; Animals ; Familial Hypophosphatemic Rickets/metabolism* ; Bone and Bones/metabolism* ; Tooth/metabolism* ; Periodontal Ligament/metabolism*

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*