choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome

Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome is a very rare multisystem condition that primarily affects structures of the head and neck, the endocrine system, and overall growth. It is caused by changes in the KMT2D gene and follows an autosomal dominant pattern of inheritance, meaning one altered copy of the gene can be enough to cause the disorder. Signs are usually noticeable in infancy or early childhood when breathing problems due to choanal atresia, absent or small nipples, or thyroid dysfunction prompt medical evaluation. Fewer than one in a million people are thought to be affected worldwide, and severity and symptoms vary widely between individuals.

The clinical picture centers on craniofacial and endocrine findings. Many newborns have bilateral choanal atresia, a blockage at the back of the nasal passages that can cause noisy breathing or feeding difficulties. Athelia or hypoplastic nipples are common clues, and some infants show branchial sinus tracts, neck pits, or lacrimal duct problems. Thyroid abnormalities may lead to congenital hypothyroidism, while delayed puberty and short stature become evident later in childhood. Hearing loss is frequent and can be related to external ear differences such as microtia or preauricular pits, and some children have facial asymmetry, down-slanted eyelid openings, or a prominent forehead. Less commonly reported findings include gastroesophageal reflux, broad big toes, single transverse palmar creases, or sparse hair and eyebrows. Not all individuals experience all features, and the type and severity of symptoms can vary considerably, even within the same family.

This condition results from pathogenic variants in the KMT2D gene. KMT2D provides instructions for a protein that helps regulate how certain other genes turn on during early development. The disorder is inherited in an autosomal dominant manner, so a parent who carries the variant has a 50% chance of passing it to each child. Some affected individuals may be the first in their family with the variant (a de novo change), and those individuals can still transmit the variant to their own children. While most people with a pathogenic variant show signs of the condition, the specific symptoms and their severity show variable expressivity. Genetic counseling is recommended for families to discuss testing and reproductive options.

Currently, management focuses on supportive care and symptom management tailored to each person’s needs. Surgical repair of choanal atresia may be required soon after birth to secure the airway, and thyroid hormone replacement treats hypothyroidism effectively. Hearing aids or other auditory interventions address hearing loss, while endocrinology teams oversee growth monitoring and management of delayed puberty. Because multiple organ systems can be involved, care is best coordinated through a multidisciplinary team that may include otolaryngologists, endocrinologists, audiologists, surgeons, and genetic specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications such as recurrent ear infections, growth delays, or evolving endocrine issues before they become serious. Families should work closely with their healthcare providers to develop an individualized monitoring schedule and discuss available therapies.

With timely surgical intervention for airway obstruction, appropriate thyroid replacement therapy, and attentive multidisciplinary follow-up, many individuals achieve good overall health and development, although short stature and hearing challenges may persist. Outcomes depend on which features are present, the age at which treatment begins, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and clinical specialists familiar with this syndrome to plan ongoing management and address family planning questions.