Although, Facio-auriculo-vertebral sequence (FAVS) is a well recognized condition with cranio-facial, ocular and vertebral anomalies, extreme variability of expression is characteristic. Association of cardiac, CNS, lungs, kidneys and limb defects are described. We report a neonatal case with FAVS in association with congenital hypoparathyroidism.

Key words: Branchial arch anomaly, Congenital hypoparathyroidism, Embryology, Facio-auriculo-vertebral sequence.

A 15-day-old neonate, second child of a non- consanguineous marriage, presented to us with two days history of multiple brief episodes of seizures. On clinical examination, baby had facial asymmetry with hypoplasia of the right mandible and right macrostomia, cleft palate, small deformed and very low set right pinna with a pre- auricular tag and atresia of the right external auditory canal (Fig. 1). Apart from anti-mongoloid slant and hypertelorism, both the eyes were normal. The neonatal reflexes (including Moro’s, sucking, rooting, etc) and other systemic examination were normal.

Fig. 1 Clinical photograph showing right microtia, mandibular hypoplasia and macrostomia and facial asymmetry suggestive of FAVS.

On evaluation, his sepsis screen (including total white cell count, band count, random blood sugar, C- reactive proteins, blood culture and CSF study) was negative. Biochemical evaluation revealed a serum calcium concentration of 6 mg /dL, the serum phosphorus concentration of 11 mg /dL and serum alkaline phosphatase concentration of 150 U/L. The serum concentration of magnesium was 1.8 mg /dL, the serum concentration of 25-hydroxyvitamin D was 7 ng /ml (normal range- 5-42) and the serum concentration of 1,25- dihydroxyvitamin D was 48 pg /mL (normal range- 8- 72). The serum concentration of the intact parathyroid hormone (PTH) was undetectable (done by intact PTH immunometric assay).

The above clinical, biochemical and radiological findings were suggestive of Facio-auriculo-vertebral syndrome with associated congenital hypopara-thyroidism. The baby was treated with intravenous 10% calcium gluconate 2 mL/kg /dose (infused at a rate of 0.5 - 1 mL/min with heart rate monitoring) eight hourly for three days and oral calcitriol 0.1 micro gm (1 mL) 12 hourly. Subsequently, the baby was discharged on oral calcitriol and supplemental calcium.

FAVS occurs as a result of abnormality in the morphogenesis of the first and the second branchial arches [1,2]. It is a well-recognized condition characterised by cranio-facial, ocular and vertebral anomalies. In addition, a more complex phenotype with skeletal, cardiac, pulmonary, renal and CNS manifestations is also known to occur [3,4]. Congenital hypoparathyroidism with FAVS has not yet been reported in the literature with the exception of a fetal autopsy case report [5].

The parathyroid glands develop from the third and the fourth branchial arches [6]. Congenital absence of the parathyroid glands with facial anomalies is known to occur with branchial arch anomalies. Thus, embryo- logically it is possible that a developmental malformation sequence involving the branchial arches may result in FAVS and agenesis or hypoplasia of the parathyroid glands (either isolated or as a part of DiGeorge sequence) and hence, congenital hypoparathyroidism could be a part of the same sequence that leads to FAVS. It should also be noted that, embryologically FAVS is considered an anomaly of first and second branchial arches, but this alteration does not explain the associated anomalies in the heart, kidneys, lungs, CNS or vertebrae. Hence, extreme variability of expression is characteristic of FAVS.

Early detection and effective treatment of congenital hypoparathyroidism prevents the potentially debilitating physical and mental retardation, including refractory seizure disorder. Embryologically there is a probability of having agenesis or hypoplasia of the parathyroid glands with defects of the branchial arches such as in FAVS. Hence, all babies of FAVS should have an estimation of serum calcium and phosphorus as a screening test, so that physical and mental retardation could be prevented.

Contributors: MP: diagnosis, management, preparing and drafting of manuscript, literature search and guarantor; SP: preparing and drafting of the manuscript.

Funding: None;Competing interests: None stated.

1. Gorlin RJ, Jue KL, Jacobsen U, Goldschmidt E. Oculoauriculovertebral dysplasia. J Pediatr. 1963;63:991-9.

2. Gorlin RJ, Cohen Jr MM, Hennekam RCM. Branchial arch and oro- acral disorders. In: Syndromes of the head and neck, 4th ed. New York: Oxford University Press; 2001. p. 790-7.

3. Cohen Jr MM, Rollnick BR, Kaye CI. Oculoauriculovertebral spectrum: an updated critique. Cleft Palate J. 1989;26:276- 86.

4. Rollnick BR, Kaye CI, Nagatoshi K, Hauck W, Martin AO. Oculoauriculovertebral dysplasia and variants: phenotypic characteristics of 294 patients. Am J Med Genet. 1987;26:361-75.

5. Pillay K, Matthews LS, Wainwright HC. Facio- auriculo- vertebral sequence in association with DiGeorge sequence, Rokitansky sequence, and Dandy Walker malformation: case repuoiort. Pediatr Dev Pathol. 2003;6:355-60.