ESPE Abstracts

Objective: Antley-Bixler syndrome Type 1 (ABS1) is a rare form of craniosynostosis characterized by multiple dysmorphic features, radio-humeral synostosis and urogenital abnormalities due to P450 oxidoreductase (POR) gene mutations. ABS is also associated with adrenal and gonadal failure which are sometimes underrecognized due to predominance of skeletal findings in various clinics. We report a female patient with very characteristic skeletal and facial features of ABS due to a homozygous POR mutation. Her diagnosis has been established while evaluating the etiology of primary amenorrhea at 16 years of age.

Case: A sixteen years old girl was referred to our clinic for primary amenorrhea. She was born to parents from close villages at 39 weeks gestation with a birth weight of 3400 g. The pregnancy was normal, and no virilization of the mother was detected. She was diagnosed with nephrolcalcinosis in 2008 and recurrent urinary tract infections were noted. At the presentation, facial dysmorphism including retro-micrognathia, high arched palate, and low-set deformed ears and multiple skeletal abnormalities such as bilateral radio-humeral synostosis, hallux longus, arachnondatyly, shortening of the fourth metatarsal bones, pes planus, kyphoscoliosis, bilateral elbow dysplasia, were observed. Laboratory investigations showed high FSH (21.5 mIU/ml), LH (12.6 mIU/ml) and progesterone (38.9 ng/ml) levels, and, normal thyroid function test with normal sodium (137 mmol/L) and potassium (4.6 mmol/L)levels. Ultrasonography revealed normaluterus and ovaries but 6 mm neprocalcinosis in right kidney. High dose synacthen test revealed an exaggerated 17-hydroxyprogesterone, progesterone and a blunted cortisol response. Urinary steroid profiling by gas chromatography-mass spectrometry (GC-MS) and plasma steroid panel revealed a unique steroid metabolome suggestive of POR deficiency. Hydrocortisone and combined estrogen and progesterone treatments were initiated. POR gene sequencing revealed a homozygous c.859G>C (p.A287P) mutation.

Conclusion: ABS should be kept in mind in the differential diagnosis of skeletal dysplasia. Impaired adrenal and gonadal steroidogenesis are important considerations for the clinicians dealing with ABS for early treatment.