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Case Reports
. 2017:2017:1.
doi: 10.1186/s13633-016-0041-7. Epub 2017 Jan 25.

Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation in FAM111A gene

Mary B Abraham  1   2 , Dong Li  3 , Dave Tang  4 , Susan M O'Connell  1 , Fiona McKenzie  2   5 , Ee Mun Lim  6   7   8 , Hakon Hakonarson  3   9   10 , Michael A Levine  9   11   12 , Catherine S Choong  1   2   13
Affiliations
Case Reports

Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation in FAM111A gene

Mary B Abraham et al. Int J Pediatr Endocrinol. 2017.

Abstract

Background: Hypoparathyroidism in children is a heterogeneous group with diverse genetic etiologies. To aid clinicians in the investigation and management of children with hypoparathyroidism, we describe the phenotype of a 6-year-old child with hypoparathyroidism and short stature diagnosed with Kenny-Caffey syndrome (KCS) Type 2 and the subsequent response to growth hormone (GH) treatment.

Case presentation: The proband presented in the neonatal period with hypocalcemic seizures secondary to hypoparathyroidism. Her phenotype included small hands and feet, hypoplastic and dystrophic nails, hypoplastic mid-face and macrocrania. Postnatal growth was delayed but neurodevelopment was normal. A skeletal survey at 2 years of age was suggestive of KCS Type 2 and genetic testing revealed a novel de novo heterozygous mutation c.1622C > A (p.Ser541Tyr) in FAM111A. At 3 years and 2 months, her height was 80cms (SDS -3.86). She had normal overnight GH levels. GH therapy was commenced at a dose of 4.9 mg/m2/week for her short stature and low height velocity of 5cms/year. At the end of the first and second years of GH treatment, height velocity was 6.5cms/year and 7.2cms/year, respectively with maximal dose of 7.24 mg/m2/week.

Conclusion: This case highlights the phenotype and the limited response to GH in a child with genetically proven KCS type 2. Long-term registries monitoring growth outcomes following GH therapy in patients with rare genetic conditions may help guide clinical decisions regarding the use and doses of GH in these conditions.

Keywords: FAM111A gene; Genetics; Growth hormone; Hypoparathyroidism; Kenny-Caffey syndrome Type 2; Short stature.

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Figures

Fig. 1
Fig. 1
Figures 1a and 1b demonstrate the facial phenotype of the patient. Large head with persistent fontanels, telecanthus, small palpebral fissures, small pinched upturned nose with elfin facies. Figure 1c demonstrates the significant growth restriction at 3 years and 2 months of age
Fig. 2
Fig. 2
Figures 2a and 2b demonstrate the small hands and feet respectively with triangular dysplastic nails
Fig. 3
Fig. 3
Figure 3 demonstrates the growth and the response of the patient to growth hormone (plotted on the CDC growth chart). Inset: Height SDS following growth hormone therapy
Fig. 4
Fig. 4
Figure 4 shows the head circumference of the patient
Fig. 5
Fig. 5
Figure 5 shows the overnight growth hormone (GH) test. Blood sample is collected every 20 min for GH and the physiological surge in GH is profiled. GH levels during waking hours are normally low. During sleep, there are usually several pulses of GH >20 mU/L (7.7 μg/L), usually associated with slow wave sleep. A peak GH response <10 mU/L (3.9 μg/L) suggests GH deficiency; a response of 10–20 mU/L (3.9–7.7 μg/L) may suggest partial GH deficiency; a response >20 mU/L (>7.7 μg/L) is regarded as normal.(1 mU/L × 0.385 = 1 μg/L)
Fig. 6
Fig. 6
Figure 6a shows relatively poor ossification of skull vault, patent metopic suture, widely separated sagittal sutures on anteroposterior view of X-ray Skull. Figure 6b shows tubulated long bones with reduced medullary space and cortical thickening on anteroposterior view X-ray Tibia
Fig. 7
Fig. 7
Figure 7a shows the FAM111A protein and Figures 7b and c show the 3D model. a The FAM111A protein is made up of 611 amino acid residues. Residues 329 to 492 and 529 to 603 are part of an InterPro domain named Peptidase S1, PA clan (IPR009003). Our novel variant p.Ser541Tyr lies in the same domain as a previously identified genetic variant, p.Arg569His, which has been associated with KCS Type 2. b and c SWISS-MODEL was used to generate a putative 3D model of FAM111A using the model template 4ic6.1, a protease that had the highest sequence identity (23.79%) to FAM111A. Only the peptidase domain of FAM111A could be modelled. Residue Ser541 is shown in 5B and Arg569 in Figure 7c
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References

    1. Cho WI, Yu HW, Chung HR, et al. Clinical and laboratory characteristics of neonatal hypocalcemia. Ann pediatr endocrinol metab. 2015;20:86–91. doi: 10.6065/apem.2015.20.2.86. - DOI - PMC - PubMed
    1. Park SY, Eom YS, Choi B, et al. Genetic and clinical characteristics of Korean patients with isolated hypoparathyroidism: from the Korean hypopara registry study. J Korean med sci. 2013;28:1489–1495. doi: 10.3346/jkms.2013.28.10.1489. - DOI - PMC - PubMed
    1. Kim JH, Shin YL, Yang S, et al. Diverse genetic aetiologies and clinical outcomes of paediatric hypoparathyroidism. Clin endocrinol (Oxf) 2015;83(6):790–796. doi: 10.1111/cen.12944. - DOI - PubMed
    1. Unger S, Gorna MW, Le Bechec A, et al. FAM111A mutations result in hypoparathyroidism and impaired skeletal development. Am j hum genet. 2013;92:990–995. doi: 10.1016/j.ajhg.2013.04.020. - DOI - PMC - PubMed
    1. Parvari R, Hershkovitz E, Grossman N, et al. Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome. Nat genet. 2002;32:448–452. doi: 10.1038/ng1012. - DOI - PubMed

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