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

Abstract

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). In this review, we reported the first Chinese patients, a pair of monozygotic twins, with genetically confirmed KCS type 2 with over 20 years follow‐up. We summarized the clinical features of 14 previously reported and genetically confirmed KCS type 2 patients; our twin patients exhibited a unique spinal manifestation which could be an important age‐dependent feature of KCS type 2. In this review, over 60% KCS type 2 patients had dental problem and over 80% suffered from refractive errors or structural eye abnormalities. Therefore, early dental, ophthalmological, and orthopedic assessments are warranted for KCS type 2 patients. Micro‐orchidism, previously reported in KCS type 2 patients, was also detected in our patients. The possibility of subfertility should be considered in male KCS type 2 patients. A multidisciplinary management approach for this rare syndrome is recommended.

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

“…Most variants are clustered together near the protein C-terminus, and a definite genotype-phenotype correlation, explaining the different severity of OCS and KCS, has not been established yet. [33], Ser541Tyr/Pro were reported in [5,32], respectively, Tyr562Ser was reported in [21], while all other variants were observed at the Laboratory of Genetics at CHUV ( [7] and this report). The domain in orange has homology to trypsin-like peptidases, including an untested catalytic triad purportedly composed of Ser541/His385/Asp439 (red bars).…”

“… Scheme of the FAM111A protein and known pathogenic variants associated with either osteocraniostenosis (OCS, top ) or Kenny-Caffey syndrome (KCS, bottom ). Cys485Phe was reported in [ 33 ], Ser541Tyr/Pro were reported in [ 5 , 32 ], respectively, Tyr562Ser was reported in [ 21 ], while all other variants were observed at the Laboratory of Genetics at CHUV ([ 7 ] and this report). The domain in orange has homology to trypsin-like peptidases, including an untested catalytic triad purportedly composed of Ser541/His385/Asp439 (red bars).…”

“…KCS patients, recently reviewed by Cheng et al, have a milder phenotype overall [ 32 ]. They share elements of defective mineralization with OCS, but at the milder end of the spectrum, with features such as delayed closure of the anterior fontanelle rather than severely decreased skull ossification [ 7 , 32 ].…”

“…KCS patients, recently reviewed by Cheng et al, have a milder phenotype overall [ 32 ]. They share elements of defective mineralization with OCS, but at the milder end of the spectrum, with features such as delayed closure of the anterior fontanelle rather than severely decreased skull ossification [ 7 , 32 ]. KCS patients are characterized by hypoparathyroidism and hypocalcemia; low calcium levels have also been detected in OCS cases, supporting the hypothesis of a PTH dysfunction underlying both conditions [ 7 ].…”

Hereditary kidney diseases associated with hypomagnesemia

“…FAM111A mutations identified in patients usually appear de novo , but some cases with autosomal dominant inheritance have been described [ 84 ]. These mutations affect the peptidase domain of FAM111A and may impair its catalytic activity [ 83 , 85 ].…”