BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation.
METHODS: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS.
CONCLUSIONS: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Bosma arhinia microphthalmia syndrome (BAMS) is a rare condition, with about 100 cases identified worldwide. It is characterized by nasal and ophthalmic abnormalities, as well as disturbances in puberty and sexual development. The cardinal sign is arhinia, though some cases have partial aplasia of the external nose. In addition, several reports have revealed abnormal brain structure, including changes to the olfactory bulbs. This case describes a 29-year-old female who has suffered from BAMS since birth. On presentation, she was noted to have congenital arhinia, bilateral microphthalmia, vision loss, mouth-breathing, an unclear speaking voice, a high arched or cleft palate, and a hypoplastic maxilla. Her paranasal sinuses were ossified and underdeveloped. This syndrome occurs rarely, both within Vietnam and worldwide. It is characterized by four major features: arrhinia, complete absence of the paranasal sinuses, eye defects, and absent sexual maturation. This case report describes the presentation of the disorder to improve otolaryngologists\' understanding of BAMS. Criteria for diagnosis consist of arhinia, midface hypoplasia (with a hypoplastic maxilla), hypogonadotropic hypogonadism, and normal intellectual abilities. Additional important findings are microphthalmia with or without coloboma, anosmia, maxillary hypoplasia, a high-arched palate, and absence of paranasal sinuses and olfactory bulbs.

Arhinia is a rare congenital anomaly that is not typically associated with known genetic mutations and is usually discovered after an affected infant is born. Prenatal diagnosis is important because neonates with arhinia often require specialized respiratory support with creation of an artificial airway. We present a case of isolated arhinia diagnosed on second-trimester ultrasound. A patient presented for routine ultrasound at 18 weeks gestation, and nasal tissues were absent in an otherwise morphologically normal appearing fetus. Cell free fetal DNA was unremarkable. The patient elected to undergo termination of pregnancy by dilation and evacuation. Subsequent genetic analysis confirmed a normal fetal karyotype and microarray, and no examination of fetal structural anatomy was possible. Antenatal diagnosis of arhinia is important to guide maternal-fetal care decisions and requires methodical sonographic evaluation to identify this malformation prior to delivery.

Bosma arhinia microphthalmia syndrome (Bosma syndrome)(OMIM 603457) is a congenital condition characterized by microphthalmia with coloboma, arhinia and endocrine findings in the setting of normal intelligence and brain structure. This condition is quite rare with fewer than 50 case reports and series. Although pathogenesis is presumed to be genetic, the cause remains unknown. We report an individual with Bosma syndrome who had bilateral colobomatous microphthalmia, arhinia, high arched palate, mild ear malformations, and hypogonadotropic hypogonadism requiring growth hormone treatment in childhood, and normal intelligence. Clinical evaluation was significant for a geometrically abnormal aorta with effacement of the sinotubular ridge, a finding not previously reported in this condition. An MRI revealed absent olfactory bulbs. Suggested criteria for diagnosis of Bosma should include arhinia, hypoplastic maxilla, normal cognition, and hypogonadotropic hypogonadism in males.