706 results match your criteria Infantile Cortical Hyperostosis

FAM111A is dispensable for electrolyte homeostasis in mice.

Sci Rep 2022 Jun 17;12(1):10211. Epub 2022 Jun 17.

Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Autosomal dominant mutations in FAM111A are causative for Kenny-Caffey syndrome type 2. Patients with Kenny-Caffey syndrome suffer from severe growth retardation, skeletal dysplasia, hypoparathyroidism, hypocalcaemia, hyperphosphataemia and hypomagnesaemia. While recent studies have reported FAM111A to function in antiviral response and DNA replication, its role in regulating electrolyte homeostasis remains unknown. Read More

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Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Calcif Tissue Int 2022 Jul 25;111(1):102-106. Epub 2022 Mar 25.

Endocrinology Unit, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c. Read More

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Clinical and Molecular Diagnosis of Osteocraniostenosis in Fetuses and Newborns: Prenatal Ultrasound, Clinical, Radiological and Pathological Features.

Genes (Basel) 2022 01 28;13(2). Epub 2022 Jan 28.

Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Osteocraniostenosis (OCS, OMIM #602361) is a severe, usually lethal condition characterized by gracile bones with thin diaphyses, a cloverleaf-shaped skull and splenic hypo/aplasia. The condition is caused by heterozygous mutations in the gene and is allelic to the non-lethal, dominant disorder Kenny-Caffey syndrome (KCS, OMIM #127000). Here we report two new cases of OCS, including one with a detailed pathological examination. Read More

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January 2022

Wnt/β-catenin Signaling Controls Maxillofacial Hyperostosis.

J Dent Res 2022 Jul 3;101(7):793-801. Epub 2022 Feb 3.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.

The roles of Wnt/β-catenin signaling in regulating the morphology and microstructure of craniomaxillofacial (CMF) bones was explored using mice carrying a constitutively active form of β-catenin in activating Dmp1-expressing cells (e.g., daβcat mice). Read More

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Differential Diagnosis between Child Abuse and Infantile Cortical Hyperostosis: A Case Report and Literature Review.

Int J Environ Res Public Health 2021 11 22;18(22). Epub 2021 Nov 22.

Department of Orthopaedic Surgery, Soonchunhyang University Hospital Cheonan, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Korea.

Child abuse is a major public health problem that can lead to critical consequences for the child and family. However, early identification of abuse may be difficult. An 8-month-old boy presented with extensive periosteal reaction in both upper and lower long bones. Read More

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November 2021

Therapeutic success of sodium thiosulfate in treating cutaneous calciphylaxis in a patient with hyperphosphataemic familial tumoral calcinosis.

Australas J Dermatol 2022 Feb 24;63(1):e75-e77. Epub 2021 Nov 24.

Departament of Metabolism, Hospital Universitario Central de Asturias, Oviedo, Spain.

Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Read More

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February 2022

PTH and FGF23 Exert Interdependent Effects on Renal Phosphate Handling: Evidence From Patients With Hypoparathyroidism and Hyperphosphatemic Familial Tumoral Calcinosis Treated With Synthetic Human PTH 1-34.

J Bone Miner Res 2022 02 15;37(2):179-184. Epub 2021 Sep 15.

Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Read More

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February 2022

Caffey disease is associated with distinct arginine to cysteine substitutions in the proα1(I) chain of type I procollagen.

Genet Med 2021 12 16;23(12):2378-2385. Epub 2021 Jul 16.

Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium.

Purpose: Infantile Caffey disease is a rare disorder characterized by acute inflammation with subperiosteal new bone formation, associated with fever, pain, and swelling of the overlying soft tissue. Symptoms arise within the first weeks after birth and spontaneously resolve before the age of two years. Many, but not all, affected individuals carry the heterozygous pathogenic COL1A1 variant (c. Read More

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December 2021

Primary hyperphosphatemic tumoral calcinosis: a case report.

Osteoporos Int 2022 Jan 10;33(1):309-312. Epub 2021 Jul 10.

Department of Orthopedics, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.

Tumoral calcinosis (TC) is a rare disease characterized by periarticular soft tissue calcification. Some cases were reported in Africa and the Middle East. We report an 11-year-old Chinese girl presenting with recurrent multiple subcutaneous masses around the right elbow and hip regions. Read More

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January 2022

Oral rehabilitation of a patient with Kenny-Caffey syndrome using telescopic overdenture.

J Indian Prosthodont Soc 2021 Apr-Jun;21(2):204-207

Department of Prosthodontics and Crown and Bridge, KMCT Dental College, Kozhikode, Kerala, India.

Kenny-Caffey syndrome (KCS) is a rarely reported autosomal disorder characterized by skeletal, ocular, and oral manifestations. Oral features such as microdontia, hypodontia, malalignment of teeth, bone loss, and difficulty in mastication results in serious esthetic and functional handicap. The prosthetic rehabilitation of such patients is challenging, especially when implant placement is not a good choice due to poor Vitamin D levels. Read More

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Report of a novel variant in the FAM111A gene in a fetus with multiple anomalies including gracile bones, hypoplastic spleen, and hypomineralized skull.

Am J Med Genet A 2021 06 22;185(6):1903-1907. Epub 2021 Mar 22.

Maternal Fetal Medicine Division, Department of Obstetrics and Gynecology, College of Medicine, University of South Florida, Tampa, Florida, USA.

Kenny-Caffey syndrome type 2 (KCS2) and osteocraniostenosis (OCS) are allelic disorders caused by heterozygous pathogenic variants in the FAM111A gene. Both conditions are characterized by gracile bones, characteristic facial features, hypomineralized skull with delayed closure of fontanelles and hypoparathyroidism. OCS and KCS2 are often referred to as FAM111A-related syndromes as a group; although OCS presents with a more severe, perinatal lethal phenotype. Read More

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The Successful Treatment of Deep Soft-tissue Calcifications with Topical Sodium Thiosulphate and Acetazolamide in a Boy with Hyperphosphatemic Familial Tumoral Calcinosis due to a Novel Mutation in

J Clin Res Pediatr Endocrinol 2022 06 9;14(2):239-243. Epub 2021 Mar 9.

Atatürk University Faculty of Medicine, Department of Pediatrics, Erzurum, Turkey

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder. Topical sodium thiosulfate (STS) and acetazolamide can be a safe and effective treatment for patients who do not respond to conventional therapy for ectopic calcifications. We report the successful treatment of deep soft-tissue calcifications with topical STS and acetazolamide in a boy diagnosed with HFTC due to a novel homozygous mutation of . Read More

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Beneficial Response to Phosphate Lowering Therapy in Normophosphatemic Tumoral Calcinosis.

Indian Pediatr 2021 01;58(1):88-89

Department of Endocrinology and Metabolism, Government Medical College, Thiruvananthapuram, Kerala, India.

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January 2021

FAM111A induces nuclear dysfunction in disease and viral restriction.

EMBO Rep 2021 02 28;22(2):e50803. Epub 2020 Dec 28.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.

Mutations in the nuclear trypsin-like serine protease FAM111A cause Kenny-Caffey syndrome (KCS2) with hypoparathyroidism and skeletal dysplasia or perinatally lethal osteocraniostenosis (OCS). In addition, FAM111A was identified as a restriction factor for certain host range mutants of the SV40 polyomavirus and VACV orthopoxvirus. However, because FAM111A function is poorly characterized, its roles in restricting viral replication and the etiology of KCS2 and OCS remain undefined. Read More

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February 2021

Adult Chinese twins with Kenny-Caffey syndrome type 2: A potential age-dependent phenotype and review of literature.

Am J Med Genet A 2021 02 1;185(2):636-646. Epub 2020 Dec 1.

Clinical Genetic Service, Department of Health, HKSAR, Hong Kong, Hong Kong.

Kenny-Caffey syndrome (KCS) type 2 (OMIM 127000) is a rare syndromic cause of hypoparathyroidism which is characterized by proportionate short stature, long bone abnormalities, delayed closure of anterior fontanelle, eye abnormalities, and normal intelligence. It is caused by variants in FAM111A (NM_001942519.1). Read More

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February 2021

FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho.

Proc Natl Acad Sci U S A 2020 12 30;117(50):31800-31807. Epub 2020 Nov 30.

Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510;

The three members of the endocrine-fibroblast growth factor (FGF) family, FGF19, 21, and 23 are circulating hormones that regulate critical metabolic processes. FGF23 stimulates the assembly of a signaling complex composed of α-Klotho (KLA) and FGF receptor (FGFR) resulting in kinase activation, regulation of phosphate homeostasis, and vitamin D levels. Here we report that the C-terminal tail of FGF23, a region responsible for KLA binding, contains two tandem repeats, repeat 1 (R1) and repeat 2 (R2) that function as two distinct ligands for KLA. Read More

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December 2020

Cortical hyperostosis, rare adverse effect of prostaglandin.

Med J Malaysia 2020 11;75(6):748-749

Penang Hospital, Department of Paediatric Cardiology, Georgetown, Penang, Malaysia.

We describe here an infant girl with ductal dependent complex cyanotic heart disease, who required prostaglandin infusion for a total of five months prior to Blalock-Taussig shunt procedure. Her alkaline phosphatase activity was raised after seven weeks being on prostaglandin and only dropped to the normal range seven days after discontinuing prostaglandin infusion. During our review at five months old, her limbs were grossly swollen and radiographic examination showed dense periosteal reaction in the long bones. Read More

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November 2020

Overlapping phenotype comprising Kenny-Caffey type 2 and Sanjad-Sakati syndromes: The first case report.

Am J Med Genet A 2020 12 3;182(12):3029-3034. Epub 2020 Oct 3.

Department of Medical Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Kenny-Caffey syndrome (KCS) is a rare hereditary skeletal disorder involving hypoparathyroidism. The autosomal dominant form (KCS2), caused by heterozygous pathogenic variants in the FAM111A gene, is distinguished from the autosomal recessive form (KCS1) and Sanjad-Sakati syndrome (SSS), both caused by pathogenic variants in the tubulin folding cofactor E (TBCE) gene, by the absence of microcephaly and intellectual disability. We present a patient with KCS2 caused by a de novo pathogenic variant c. Read More

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December 2020


J Paediatr Child Health 2020 08;56(8):1321-1323

From Pediatric Allergy Immunology Unit, Department of Pediatrics, Advances Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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FAM111 protease activity undermines cellular fitness and is amplified by gain-of-function mutations in human disease.

EMBO Rep 2020 10 9;21(10):e50662. Epub 2020 Aug 9.

Protein Signaling Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.

Dominant missense mutations in the human serine protease FAM111A underlie perinatally lethal gracile bone dysplasia and Kenny-Caffey syndrome, yet how FAM111A mutations lead to disease is not known. We show that FAM111A proteolytic activity suppresses DNA replication and transcription by displacing key effectors of these processes from chromatin, triggering rapid programmed cell death by Caspase-dependent apoptosis to potently undermine cell viability. Patient-associated point mutations in FAM111A exacerbate these phenotypes by hyperactivating its intrinsic protease activity. Read More

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October 2020

Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management.

Front Endocrinol (Lausanne) 2020 8;11:293. Epub 2020 May 8.

Skeletal Disorders and Mineral Homeostasis Section, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare and disabling disorder of fibroblast growth factor 23 (FGF23) deficiency or resistance. The disorder is manifest by hyperphosphatemia, inappropriately increased tubular reabsorption of phosphate and 1,25-dihydroxy-Vitamin D, and ectopic calcifications. HFTC has been associated with autosomal recessive pathogenic variants in: (1) the gene encoding FGF23; (2) , which encodes a protein responsible for FGF23 glycosylation; and (3) , the gene encoding KLOTHO, a critical co-receptor for FGF23 signaling. Read More

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Kenny-Caffey syndrome type 2.

QJM 2021 07;114(4):267-269

Department of Biochemistry, Shree Narayana Institute of Medical Superspeciality, Nanded, Maharashtra 431602, India.

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Defective O-glycosylation of novel FGF23 mutations in a Chinese family with hyperphosphatemic familial tumoral calcinosis.

Bone 2020 08 1;137:115401. Epub 2020 May 1.

Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Objectives: Hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome (HFTC/HHS) is a rare disorder caused by deficiency or resistance of fibroblast growth factor 23 (FGF23). Here we reported a Chinese family with HFTC/HHS, aiming at clarifying the clinical features, bone microarchitectures and molecular mechanisms of the disease.

Methods: Clinical manifestations, laboratory examinations and genetic analyses were collected from two HFTC patients. Read More

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Kenny-Caffey Syndrome Type 2: A Unique Presentation and Craniofacial Analysis.

J Craniofac Surg 2020 Jul-Aug;31(5):e471-e475

Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Division of Plastic Surgery, Texas Children's Hospital, Houston, TX.

Kenny-Caffey Syndrome Type 2 (KCS2) is a rare genetic disorder characterized by short stature, skeletal dysplasia, primary hypoparathyroidism, and delayed closure of the anterior fontanelle. Patients with KCS2 typically require multidisciplinary management due to numerous craniofacial and skeletal anomalies. Craniosynostosis, however, has not yet been identified in a patient with KCS2 to the best of our knowledge. Read More

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November 2020

Caffey Disease in Infancy: A diagnostic dilemma for primary care physicians.

Sultan Qaboos Univ Med J 2020 Feb 9;20(1):e109-e111. Epub 2020 Mar 9.

Department of Pediatrics, Sarojini Naidu Children Hospital, Moti Lal Nehru Medical College, Allahabad, India.

Caffey disease is a rare and self-limiting condition characterised by cortical hyperostosis with inflammation of adjacent and muscles. It usually presents in infancy and clinical features include hyperirritability, acute inflammation with swelling of overlying soft tissues and subperiosteal new bone formation. Awareness of the existence of this rare condition and its typical clinical and radiological profile will avoid unnecessary investigations and treatment and help the physician to explain its good prognosis to parents of affected children. Read More

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February 2020

Hyperphosphatemic familial tumoral calcinosis caused by a novel variant in the GALNT3 gene.

J Endocrinol Invest 2020 Aug 3;43(8):1125-1130. Epub 2020 Mar 3.

Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, No 10, Firoozeh St, Vali-asr Sq, Tehran, Iran.

Aim: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare endocrine disorder caused by autosomal recessive variants in GALNT3, FGF23, and KL leading to progressive calcification of soft tissues and subsequent clinical effects. The aim of this was to study the cause of HFTC in an Iranian family.

Patients And Methods: Four generations of a family with HFTC were studied for understanding the genetic pattern of the disease. Read More

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Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs.

Genes (Basel) 2020 02 4;11(2). Epub 2020 Feb 4.

Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of has been reported so far only in three Terrier breeds. Read More

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February 2020

Congenital Hyperphosphatemic Conditions Caused by the Deficient Activity of FGF23.

Calcif Tissue Int 2021 01 22;108(1):104-115. Epub 2020 Jan 22.

Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.

Congenital diseases that could result in hyperphosphatemia at an early age include hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) and congenital hypoparathyroidism/pseudohypoparathyroidism due to the insufficient activity of fibroblast growth factor (FGF) 23 and parathyroid hormone. HFTC/HHS is a rare autosomal recessive disease caused by inactivating mutations in the FGF23, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), or Klotho (KL) genes, resulting in the excessive cleavage of active intact FGF23 (FGF23, GALNT3) or increased resistance to the action of FGF23 (KL). Massive ectopic calcification, known as tumoral calcinosis (TC), is seen in periarticular soft tissues, typically in the hip, elbow, and shoulder in HFTC/HHS, reducing the range of motion. Read More

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January 2021

Recurrence of tumoral calcinosis: a case report.

Acta Biomed 2019 12 23;90(4):587-594. Epub 2019 Dec 23.

Radiology Department, National Cancer Institute Pascale Foundation, via M. Semmola 53, I-80131 Naples Italy.

We describe radiographic, contrast-enhanced MDCT and MRI findings with pathologic correlations of an unusual recurrence of tumoral calcinosis, also called Teutschlander disease. The disease was silent in the first decade of life, when it appeared with elbows recurring lesions, until the seventh decade of life, when a left hip active growth lesion developed. A review about tumoral calcinosis pathogenesis, clinical course and imaging differential diagnosis is reported. Read More

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December 2019