Kenny-Caffey Syndrome, Type 1

Last update 08 May 2025

Basic Info

Synonyms

Autosomal recessive Kenny-Caffey syndrome, KCS, KCS1

+ [25]

Introduction

An autosomal recessive form of Kenny-Caffey syndrome due to mutation(s) in the TBCE gene, encoding tubulin-specific chaperone E. This condition is characterized by hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space in the skull, cortical thickening of long bones with medullary stenosis, and small hands and feet.

100 Clinical Results associated with Kenny-Caffey Syndrome, Type 1

100 Translational Medicine associated with Kenny-Caffey Syndrome, Type 1

0 Patents (Medical) associated with Kenny-Caffey Syndrome, Type 1

124

Literatures (Medical) associated with Kenny-Caffey Syndrome, Type 1

24 Mar 2025·JCI Insight

Quantitative hypermorphic FAM111A alleles cause autosomal recessive Kenny-Caffey syndrome type 2 and osteocraniostenosis

Article

Author: Eason, Jacqueline ; Caswell, Richard C ; Mailand, Niels ; Levine, Michael A ; Li, Dong ; Pang, Lewis ; Ewing, Emma ; Dou, Ying ; Sullivan, Kathleen E ; Hakonarson, Hakon ; Hoffmann, Saskia

Kenny-Caffey syndrome (KCS) is a rare genetic disorder characterized by extreme short stature, cortical thickening and medullary stenosis of tubular bones, facial dysmorphism, abnormal T cell function, and hypoparathyroidism. Biallelic loss-of-function variants in TBCE cause autosomal recessive type 1 KCS (KCS1). By contrast, heterozygous missense variants in a restricted region of the FAM111A gene have been identified in autosomal dominant type 2 KCS (KCS2) and a more severe lethal phenotype, osteocraniostenosis (OCS); these variants have recently been shown to confer a gain of function. In this study, we describe 2 unrelated children with KCS and OCS who were homozygous for different FAM111A variant alleles that result in replacement of the same residue, Tyr414 (c.1241A>G, p.Y414C and c.1240T>A, p.Y414N), in the mature FAM111A protein. Their heterozygous relatives are asymptomatic. Functional studies of recombinant FAM111AY414C demonstrated normal dimerization and a mild gain-of-function effect. This study provides evidence that both biallelic and monoallelic variants of FAM111A with varying degrees of activation can lead to dominant or recessive KCS2 and OCS.

01 Feb 2025·Journal of Human Genetics

Homozygous synonymous FAM111A variant underlies an autosomal recessive form of Kenny-Caffey syndrome

Article

Author: Seif, Lara ; Abdelrazek, Ibrahim M ; Harms, Frederike Leonie ; Kutsche, Kerstin ; Bonde, Loisa Dana ; Alawi, Malik ; Nabil, Karim ; Matrawy, Khaled ; Abdalla, Ebtesam

AbstractFAM111A (family with sequence similarity 111 member A) is a serine protease and removes covalent DNA-protein cross-links during DNA replication. Heterozygous gain-of-function variants in FAM111A cause skeletal dysplasias, such as the perinatal lethal osteocraniostenosis and the milder Kenny-Caffey syndrome (KCS). We report two siblings born to consanguineous parents with dysmorphic craniofacial features, postnatal growth retardation, ophthalmologic manifestations, hair and nail anomalies, and skeletal abnormalities such as thickened cortex and stenosis of the medullary cavity of the long bones suggestive of KCS. Using exome sequencing, a homozygous synonymous FAM111A variant, NM_001312909.2:c.81 G > A; p.Pro27=, that affects the last base of the exon and is predicted to alter FAM111A pre-mRNA splicing, was identified in both siblings. We identified aberrantly spliced FAM111A transcripts, reduced FAM111A mRNA levels, and near-complete absence of FAM111A protein in fibroblasts of both patients. After treatment of patient and control fibroblasts with different concentrations of camptothecin that induces covalent DNA-protein cross-links, we observed a tendency towards a reduced proportion of metabolically active cells in patient compared to control fibroblasts. However, under these culture conditions, we did not find consistent and statistically significant differences in cell cycle progression and apoptotic cell death between patient and control cells. Our findings show that FAM111A deficiency underlies an autosomal recessive form of FAM111A-related KCS. Based on our results and published data, we hypothesize that loss of FAM111A and FAM111A protease hyperactivity, as observed for gain-of-function patient-variant proteins, may converge on a similar pathomechanism underlying skeletal dysplasias.

12 Aug 2024·Acta Oto-Laryngologica

Cochlear implantation in a familial rare syndromic ossification-related deafness and literature review

Article

Author: Li, Yongxin ; Cui, Danmo ; Kong, Ying ; Zou, Xinyue ; Chen, Biao ; Chen, Jingyuan ; Wei, Xingmei ; Shi, Ying ; Zhang, Lifang ; Liu, Ping ; Lu, Simeng

BACKGROUNDKenny-Caffey Syndrome type 2 (KCS2) is a genetic disease affecting bone metabolism. However, cochlear implantation (CI) results have yet to be published in detail.OBJECTIVEThis study presents the gene, clinical characteristics, surgical outcomes, and literature review of 2 patients with sensorineural hearing loss related to KCS2. To enhance diagnostic detection and accuracy, we also compare the differential diagnosis between KCS2, otosclerosis, and Cogan's syndrome (CS).METHODSPrior to CI, patients with KCS2 and CS underwent comprehensive audiological and radiological evaluations. Postoperative auditory speech outcomes and impedance values were recorded and analyzed statistically. A systematic search of the literature was conducted to summarize clinical characteristics.RESULTSPatients diagnosed with KCS2 exhibit more pronounced changes in the inner ear. The impedance values in the KCS2 cohort were considerably higher (Mean = 12.13 kΩ) than those with CS (Mean = 8.8 kΩ) one year post-activation. The literature review exhibits the clinical manifestations associated with KCS2.CONCLUSIONCI is an effective treatment for KCS2 to restore hearing loss. More frequent programming and accurate adjustment of stimulation is of great necessity. A thorough examination, including temporal bone HRCT, 3D-MRI, audiological evaluations, and whole-exome sequencing, is essential for the diagnosis and treatment of KCS2.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Kenny-Caffey Syndrome, Type 1

Basic Info

Related

Analysis