Clinical and genetic features of Kenny-Caffey syndrome type 2 with multiple electrolyte disturbances: A case report

Abstract

Background: Hypoparathyroidism, which can be sporadic or a component of an inherited syndrome, is the most common cause of hypocalcemia. If hypocalcemia is accompanied by other electrolyte disturbances, such as hypokalemia and hypomagnesemia, then the cause, such as renal tubular disease, should be carefully identified.

Case summary: An 18-year-old female visited our clinic because of short stature and facial deformities, including typical phenotypes, such as low ear position, depression of the nasal bridge, small hands and feet, and loss of dentition. The lab results suggested normal parathyroid hormone but hypocalcemia. In addition, multiple electrolyte disturbances were found, including hypokalemia, hypocalcemia and hypomagnesemia. The physical signs showed a short fourth metatarsal bone of both feet. The X-ray images showed cortical thickening of long bones and narrowing of the medulla of the lumen. Cranial computed tomography indicated calcification in the bilateral basal ganglia. Finally, the genetic investigation showed a de novo heterogenous mutation of "FAM111A" (c. G1706A:p.R569H). Through a review of previously reported cases, the mutation was found to be the most common mutation site in Kenny-Caffey syndrome type 2 (KCS2) cases reported thus far (16/23, 69.6%). The mutation was slightly more prevalent in females than in males (11/16, 68.8%). Except for hypocalcemia, other clinical manifestations are heterogeneous.

Conclusion: As a rare autosomal dominant genetic disease of hypoparathyroidism, the clinical manifestations of KCS2 are atypical and diverse. This girl presented with short stature, facial deformities and skeletal deformities. The laboratory results revealed hypocalcemia as the main electrolyte disturbance. Even though her family members showed normal phenotypes, gene detection was performed to find the mutation of the FAM111A gene and confirmed the diagnosis of KCS2.

Keywords: Case report; FAM111A gene; Hypocalcemia; Hypomagnesemia; Hypoparathyroidism; Kenny-Caffey syndrome type 2.

Figure 1

Special phenotypes of this 18-year-old female patient with Kenny-Caffey syndrome type 2. A: Small hands; B: Cheek freckles, high anterior hairline, sparse scalp hair, prominent forehead, depressed nasal bridge, low-set ears, small mandible, slightly higher mandibular arch, increased quilt hair; C: Feet and short in bilateral 4^th toes; D: Partially absent dentition.

Figure 2

The head computed tomography and skeletal X-ray features of the patient are indicated by arrows A–E, respectively. A: Head computed tomography (noncontrast) showing symmetrical calcifications in the cerebellar hemisphere, frontotemporal parietal lobe, basal ganglia, and thalamus; B: Digital radiography (DR) of the anteroposterior pelvis showing that the right ilium is smaller compared to the left side, as well as shallow acetabular fossa on both sides; C: DR of the left foot showing short and small 4^th and 5^th metatarsal bones and corresponding phalanges in both feet; D: The phalanges of the left little finger are short, with thickening of the cortex of the tubular bone and narrowing of the medulla; E: DR of the left lower limb showing thickening of the cortex of the tubular bone and narrowing of the medulla.

Figure 3

Genetic pedigree of the patient showing the chromatograms of Sanger sequencing results of the FAM111A mutation for the patient and her parents. Data were obtained by Sanger sequencing during the confirmation of the diagnosis. Forward sequencing was performed for the mutation. In the pedigree, the black symbols represent probands. Squares and circles represent males and females, respectively. In the chromatogram, the black letters indicate the nucleotide sequence of the wild-type, while the nucleotides in red indicate mutations. R569H was identified in all probands but not in the parents who received the sequencing tests. The younger and older sisters were phenotypically normal and did not agree to undergo Sanger sequencing.