ESPE Abstracts

We report a male patient born small for gestational age (birth weight 2090 g, -2.97 SDS; birth length 43.5 cm, -3.37 SDS), with dysmorphic features (triangular face, low-set, posteriorly rotated ears, pectus excavatum, large anterior fontanel) who presented with seizures at the age of 4 weeks. The child was treated with antiepileptic drugs (Levetiracetam, Midazolam, Phenobarbital, carbamazepine) for 1 year until a severe hypocalcemia (Calcium 6.4 mg/dl, ionised calcium 0.78 mmol/L) was discovered. Retrospectively, this hypocalcemia has already been present in the setting of his first seizure but not at birth. A further diagnostic work up revealed a low PTH (6.9 pg/ml), elevated inorganic phosphate (8.3 mg/dl) and normal vitamin D levels. A part from hypoparathyroidism, he had elevated liver enzymes (GOT 151 U/l, GPT 111 U/l, GGT 121 U/l), papillary oedema, short stature (61.5 cm height at age 1 year, -6.46 SDS), underweight (BMI at age one year, 13.2 kg/m2, -3.02 SDS) and a wide opened anterior fontanel (1.5x1.5 cm). These findings guided us to the clinical suspicion of a KCT2S, confirmed by the genetic analysis revealing a heterozygous de novo missense variant in the gene FAM111A (c.928A>C). This variant has so far not been reported in the literature. KCT2S is an autosomal dominantly inherited extremely rare (Prevalence <1 / 1 000 000) primary bone dysplasia syndrome characterized by growth retardation, cortical thickening and medullary stenosis of the long bones, delayed anterior fontanelle closure, hypocalcaemia due to congenital hypoparathyroidism and facial dysmorphism. Additional manifestations include ocular and dental anomalies, hypoplastic nails and neonatal liver disease. Since the introduction of a treatment with 1-alpha-calcidiol and calcium (current dosage 750 mg Calcium, 0.9 mg1-alpha-calcidiol/day) the calcium levels have normalised and the antiepileptic therapy could be stopped without any further seizures. EEG was normal. Liver enzymes decreased, but stayed elevated (stop of carbamazepine, liver disease in KCT2S). Papillary oedema persisted although normalised calcium (maybe ocular phenotype of KCT2S). Weight development became better under therapy (BMI at 2 years -0.95 SDS), growth remained poor (height at 2 years: 65.4 cm, -7.12 SDS). No dental or nail anomalies. Neurocognitive development is normal.

Conclusion: Hypocalcaemia is an important differential diagnosis in the setting of seizures. A rare cause of neonatal seizures can be a congenital hypoparathyroidism. We describe a patient with a KCT2S with a so far not described mutation in the FAM111A gene.