Endocrine Abstracts

JOINT269

Background: The 22q11.2 region covers approximately 30 genes, including TBX1, the mutation of which has been show to cause the 22q11.2 deletion syndrome. We report the case of a neonate with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures.

Case report: A 9-day-old female newborn was admitted to the pediatric neurological department to investigate recurrent focal tonic-clonic seizures. On admission, the physical examination was normal. The video-electroencephalography (EEG) was performed and ictal recording showed focal tonic and clonic seizures with bilateral propagation. Routine blood tests revealed hypocalcemia, total serum calcium of 1.66 mmol/l (2.15–2.8 mmol/l); and hyperphosphatemia, 3.42 mmol/l (1.25–2.5/mmol/l) with normal liver and kidney function, normal vitamin D level and negative inflammation markers. The parathyroid hormone levels were low on two occasions, 0.7 pg/ml and 0.3 pg/ml (1.3–9.3 pg/ml), respectively. The treatment consisted of controlling the seizures and correcting the hypocalcemia. A loading dose of phenobarbital (20 mg/kg) was administered, followed by oral administration. Since the seizures persisted, levetiracetam was added which led to seizure remission. The antiepileptic treatment with phenobarbital decreased serum calcium levels despite the simultaneous administration of calcium supplements. Calcium supplementation was started intravenously and, continued via the oral route. Hypoparathyroidism was transient and the treatment of hypocalcemia was stopped at the age of 2 months. Considering the association of neonatal hypocalcemia with hypoparathyroidism and seizures, DiGeorge Syndrome as well as other genetic disorders were taken into account. FISH did not reveal a 22q11.2 microdeletion. Further genetic analysis showed a novel T box-1 (TBX1) heterozygous mutation (c.337C>T; p.Gln113*). Over the next 4-month follow-up period the infant developed normally, without any seizures. EEG normalized and antiepileptic therapy was gradually discontinued.

Conclusion: A novel heterozygous TBX1 mutation was identified as a cause of neonatal hypocalcemic seizures and DiGeorge syndrome. We emphasize the importance of further genetic evaluation in infants with hypoparathyroidism without 22q11.2 deletion for detecting TBX1 mutations.