A case of antley-bixler syndrome.

Antley-Bixler syndrome (ABS) is rare form of craniosynostosis of both autosomal dominant and autosomal recessive inheritance. We are reporting a female term appropriate for gestational age newborn with clinical features of frontal bossing, brachycephaly, proptosis, synostosis of radioulnar joints, hemangioma over nose and philtrum, hydrocephalus suggestive of ABS.

INTRODUCTION

First described in 1975,[1] Antley-Bixler syndrome (ABS) is an autosomal recessive, exceptionally rare craniosynostosis syndrome characterized by radiohumeral synostosis present from the perinatal period (OMIM number #207410). Only 50 cases have been reported yet.[2] There is a wide spectrum of anomalies seen in ABS; other features include midface hypoplasia, choanal stenosis or atresia, and multiple joint contractures. Mortality has been reported to be as high as 80% in the neonatal period, primarily due to airway compromise, and prognosis improves with increasing age.[3]

CASE REPORT

A full-term appropriate for gestational age (AGA) female baby was born of non-consanguineous marriage of a primiparous mother by caesarean section. Birth weight was 2.5 kg. The newborn cried at birth. Mother had an uneventful pregnancy. There was no history of intake of fluconazole during the pregnancy. There was no history of obvious congenital anomalies or fetal loss in the family. On examination, vitals were stable. Baby has normal reflexes and sucks mother's milk well. Craniofacial abnormalities found were brachycephaly (cephalic index=95.45), frontal bossing, large anterior fontanel, open metopic suture, synostosis in sagittal and lambdoid sutures, deficient skull bones over both temporal fosse, proptosis of right eye with opacity of cornea, left eye prominent with redness of conjunctiva, low set ears, high arched palate, choanal stenosis, bilateral stenotic external auditory canal, short neck, hemangioma over nose and philtrum, and depressed nasal bridge. Inter-pupillary distance=5.5 cm (>90th percentile), Head circumference=32.5 cm (25-50th percentiles). Limb defects were radioulnar synostosis leading to fixed flexion deformity of elbow joints, fixed flexion deformity of both thumbs in proximal and distal interphalangeal joints, arachnodactyly, rocker-bottom feet, hallux varus, knee and hip joint contracture. Other abnormalities were prominent chest, female genitalia with hypoplastic labia majora [Figure 1].

Figure 1

The picture of the baby with Antley-Bixler Syndrome

Sepsis screen was positive on day four and blood culture revealed late onset sepsis by Staphylococcus aureus. 17-Alpha Hydroxyprogesterone was found to be normal at 10 ng/dl. There is no history suggestive of adrenal insufficiency. Radiological investigations showed radioulnar synostosis and arachnodactyly.[Figure 2] Ultrasonography (USG) of brain revealed ventricular dilatation. USG of abdomen was normal. Brain imaging revealed hydrocephalous of obstructive type with thickened fourth ventricle. Basal cisterns are normal. Echocardiography was normal. Patient had three episodes of apnea during the hospital stay. The baby received gentamicin and ciprofloxacin (as per culture sensitivity) for late-onset sepsis for 14 days. Above features suggest ABS. However, there were no enlarged interphalangeal joints or increased femoral bowing or fractures. At present, baby is on exclusive breast feeding. No further episode of apnea was noticed after first seven days. Occasional nasal obstruction needs treatment with saline nasal drops. Enucleation of eye has been planned.

Figure 2

X-ray showing radioulnar synostosis

DISCUSSION

Antley and Bixler (1975) described a child with “trapezoidocephaly,” midface hypoplasia, humeroradial synostosis, bowing of femora, fractures, and other abnormalities.[2] Crisponi et al. (1997) stated that since the first report by Antley and Bixler (1975) at least 23 cases had been reported. They reported an affected infant who died a few days after birth of respiratory failure. Unlike previously described cases, the elbow joint contractures in our patient were due to radioulnar synostosis rather than radiohumeral synostosis. The infant did not have long bone fractures, and the femurs were not markedly bowed.[4] Our case also did not have long bone fracture or bowing of femur. Chun et al. (1998) reported a patient with clinical manifestations that they considered consistent with ABS who carried an ser351-to-cys mutation on one allele of the fibroblast growth factor receptor 2 (FGFR2) gene.[5] Chun et al. (1998) suggested that the ABS is an autosomal dominant condition with possible gonadal mosaicism, or that alternatively, an autosomal dominant form and an autosomal recessive form of ABS may exist. However, no genetic study could be arranged for our patient. Mutations in the genes for FGFR have been reported to be involved in some craniosynostosis syndromes such as Pfeiffer, Apert, Cruzon, and Jackson-Weiss Syndromes. Mutations in the cytochrome P450 oxidoreductase gene (POR) located on chromosome 7q11.23 result in autosomal recessive inheritance and an ABS phenotype that includes genital ambiguity and characteristic urinary steroid profile.[6] In utero exposure to fluconazole[1] may be a reason. Digenic inheritance where FGFR2 mutations account for the skeletal abnormalities and different mutations causing altered steroidogenesis contribute to the genital anomalies.[1] Lehuep et al. (1995) reported two affected sibs,[7] in the first case, renal agenesis was recognized prenatally when oligohydramnios led to the sonographic diagnosis of absent kidneys during the seventh month. Clinical features were recognized by ultrasonography at 21 weeks in the second case. However, no such findings were present in our patient. Undetectable unconjugated estriol implying abnormal fetal steroid or sterol metabolism has been demonstrated at mid-gestational maternal serum screening and may provide a prenatal marker for this disorder in some cases.[8] McGlaughlin et al. (2010) noted that craniosynostosis and radiohumeral synostosis present from the perinatal period are generally considered to be the minimum criteria for a diagnosis of ABS,[3] thus helping us to diagnose the case. Respiratory compromise secondary to upper airway obstruction varies from severe nasal congestion to multiple apneic episodes leading to death in the first few months of life.[1] Our patient already had three episodes of apnea and receives saline nasal drops for nasal congestion. In future, she may need tracheostomy or placement of gastrostomy tube. Prognosis of the disease is good once the perinatal period has passed. Joint contractures have improved with age and passive range-of-motion exercises. There has been no propensity to fracture postnatally.[1] In our patient, we have planned enucleation of the right eye. Left eye is normal. In future, we may attempt resection of the radiohumeral joint. We shall follow-up the patient frequently for early diagnosis and treatment of the complications and monitor neurodevelopmental outcome.