Kenny–Caffey syndrome type 2

Hypoparathyroidism is a rare endocrine disorder of calcium homeostasis .The etiology of hypoparathyroidism in children is diverse, most of which have a genetic basis.1,2 Kenny–Caffey syndrome 2 (KCS 2) is one of the uncommon causes of hypoparathyroidism in children. It is characterized by proportionate short stature along with hypoparathyroidism, cortical thickening, medullary stenosis of tubular long bones, delayed closure of anterior fontanel and eye abnormalities.2–4 Here, we present a case of 9-year-old girl with KCS 2 who had the characteristic clinical, biochemical, radiological and genetic abnormalities of the syndrome. A 9-year-old female child presented to endocrinology Outpatient Department (OPD) with short stature and repeated carpopedal spasms. Her height was 110 cm (<3rd centile, midparental height (MPH): 75th centile) (−4.3SDS) and weight was 24 kg. There was no family history of short stature or hypoparathyroidism. Parents were clinically unaffected with maternal height of 159.8 cm and paternal height of 179.1 cm (predicted mid-parental target height: 162.9 cm). On examination, she had noticeable dysmorphic features including small palpebral fissures, long philtrum, thin upper lip, small pinched nose with relatively elfin facies (Figure 1). Physical examination showed positive Chvostek and Trousseau sign. Her biochemical evaluation revealed hypocalcemia, high normal phosphorous and inappropriately low normal parathyroid hormone (PTH) (Sr calcium—6.2 mg%, Sr phosphorous—5.8 mg% and PTH—16.4 pg/ml) (Table 1). The presence of low or normal PTH levels at the time of hypocalcemia is decidedly abnormal because under physiological conditions, hypocalcemia will lead to an increase in PTH.1 To rule out other causes of short stature, routine investigations were performed which were negative. Her skeletal survey showed cortical thickening, medullary stenosis of the long bones (Figure 2) and absence of diploic space in the skull bones (Figure 3). On revisiting the history, she had multiple episodes of hypocalcemia which required repeated admissions to pediatric unit (Table 1). She presented first time at 5 months of age with hypocalcemic seizures (serum calcium—5.7 mg%). Normocalcemia was achieved with parenteral calcium gluconate infusion. Thereafter, she was on oral elemental calcium and calcitriol. Based on her clinical, biochemical and radiological features, KCS 2 was suspected. Further genetic testing revealed a heterozygous missense variation in exon 5 of the FAM111A gene (chr11: g.58920847G>A) that results in the amino acid substitution of Histidine for Arginine at codon 569 (p.Arg569His). This variation has previously been reported in patients affected with KCS.5In silico predictions of the variant are benign by Sorting Intolerant From Tolerant (SIFT), PolyPhen-2 and MutationTaster2. Although, in silico predictions are benign, this variant was reported as a recurrent hotspot pathogenic mutation in literature. Hence, this FAM111A variation was classified as a likely pathogenic variant. An ophthalmological examination reported high hypermetropia, cornea and lens were clear. She was treated with parenteral calcium gluconate infusion and discharged on oral calcium and calcitriol supplementation. To the best of our knowledge, this is the first genetically proven case of KCS 2 from Maharashtra (India). This case highlights the clinical, biochemical and radiological characteristics of a child with KCS type 2 due to FAM111A mutation. Demonstrate the facial phenotype of the patient. Large head with small palpebral fissures, small pinched nose with elfin facies. Demonstrate the facial phenotype of the patient. Large head with small palpebral fissures, small pinched nose with elfin facies. X-ray images showing tubular long bones with reduced medullary space and cortical thickening: (a) humerus, (b) femur and (c) forearm bones. X-ray images showing tubular long bones with reduced medullary space and cortical thickening: (a) humerus, (b) femur and (c) forearm bones. X-ray showing absent diploic space in the skull bones. X-ray showing absent diploic space in the skull bones. Serial serum calcium, phosphorus, alkaline phosphatase, PTH, 25 (OH) Vit D, magnesium and urine Ca/Creat ratio Serial serum calcium, phosphorus, alkaline phosphatase, PTH, 25 (OH) Vit D, magnesium and urine Ca/Creat ratio Conflict of interest. None declared.