arhinia, choanal atresia, and microphthalmia

Arhinia, choanal atresia, and microphthalmia is a very rare multisystem condition that primarily affects development of the nose, eyes, and midface. It results from autosomal dominant changes in the SMCHD1 gene, which plays an important role in regulating how chromosomes are packaged and how certain genes are switched on or off during early development. Signs are present at birth and can affect people of any sex. Fewer than one in a million individuals are thought to have the condition worldwide, so most clinicians will encounter only isolated cases in their careers. Because outward facial differences appear early, families often seek medical attention soon after birth, but the full range of features may become clearer over time.

The most recognizable features are the near or complete absence of the external nose (arhinia) and blockage of the back of the nasal passages (choanal atresia), both of which can cause newborn breathing and feeding difficulties. Under-development of the eyes (microphthalmia) may be accompanied by coloboma or cataracts, and many children have lacrimal duct atresia that leads to excessive tearing. Craniofacial findings include midface retrusion, a high or cleft palate, dental malocclusion, and hypoplastic sinuses. Endocrine and reproductive differences are common: hypogonadotropic hypogonadism may result in cryptorchidism in boys, underdeveloped labia majora or delayed puberty in girls, and later fertility concerns. Additional variable findings can include inguinal hernias, conductive hearing impairment, atresia of the external auditory canal, synophrys, and hypospadias. Most individuals have typical intelligence, yet a minority experience intellectual or developmental challenges that may benefit from early cognitive and educational supports. Not all individuals experience all features, and severity varies considerably from one person to another.

This condition is caused by pathogenic variants in the SMCHD1 gene. The SMCHD1 protein helps control chromatin structure, influencing how other genes are expressed during embryonic development, particularly in tissues that form the face, eyes, and reproductive system. Arhinia, choanal atresia, and microphthalmia is inherited in an autosomal dominant pattern, meaning one altered copy of SMCHD1 is sufficient to cause the condition. An affected individual has a 50 percent chance of passing the variant to each child. Even within the same family, the specific features and their severity can differ markedly, a phenomenon known as variable expressivity. Because de novo (new) variants have been reported in other autosomal dominant disorders involving SMCHD1, genetic counseling is recommended to discuss testing for parents, recurrence risks, and family planning options.

Currently, management focuses on supportive care and addressing individual symptoms, as no therapies have been specifically approved for this condition. Early priorities often include securing a safe airway, which may involve surgical repair of choanal atresia or tracheostomy in severe cases. Reconstructive or prosthetic procedures can improve nasal appearance and function, though timing is tailored to growth and family preference. Ophthalmologic surgeries may address coloboma or cataracts, and hearing loss can be managed with hearing aids or canal reconstruction. Hormone replacement therapy is frequently used to induce and maintain puberty in those with hypogonadotropic hypogonadism, and fertility specialists may assist with future reproductive planning. Long-term management includes regular surveillance for potential complications. Recommended monitoring typically involves annual ophthalmologic evaluations, periodic endocrine review to adjust hormone therapy, dental and orthodontic follow-up for palate and malocclusion issues, and hearing assessments during childhood. Because care spans multiple systems, a multidisciplinary team—often including otolaryngology, craniofacial surgery, endocrinology, ophthalmology, audiology, dentistry, and genetic counseling—helps coordinate interventions and monitoring over time. Patients should discuss available options with their healthcare team to determine which approaches best meet their individual needs.

With timely airway management, hormone replacement, and ongoing specialist care, many individuals lead healthy lives and participate fully in school, work, and community activities. Nonetheless, the day-to-day impact can vary widely depending on the severity of facial differences, eye involvement, and hormonal needs. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert craniofacial and endocrine teams as well as a genetic counselor who can provide guidance on inheritance and future family planning. Support groups and patient organizations—though limited for ultra-rare conditions—can offer community connection and practical advice.