Brachydactyly Type E (BDE) is a rare, inherited congenital malformation that primarily affects the growth of bones in the hands and feet. The term itself means “short digits,” and Type E is specifically characterized by the disproportionate shortening of the long bones within the palms and soles. The bones most commonly involved are the metacarpals in the hand and the metatarsals in the foot, which connect the wrists and ankles to the fingers and toes. BDE presents a distinct pattern of bone underdevelopment that can occur either in isolation or as a feature of a broader genetic syndrome.
Identifying Brachydactyly Type E
The defining characteristic of BDE is the shortening of one or more of the metacarpal bones in the hand and metatarsal bones in the foot. This shortening most frequently involves the fourth and sometimes the fifth digit rays, making those fingers and toes appear noticeably shorter than the others. The effect is often bilateral, meaning it presents symmetrically on both sides of the body, though the severity can vary significantly.
The shortened metacarpals cause the corresponding finger to look truncated, sometimes creating a visible dimple or depression at the knuckle. This is particularly noticeable when the hand is clenched into a fist, as the affected knuckle may not protrude alongside the others. While the phalanges are generally normal in length, the overall appearance is that of small hands and feet due to the hypoplastic base bones.
The bone shortening often becomes more apparent as a child grows, typically starting around four to seven years of age or during the pubertal growth spurt. Individuals with BDE frequently present with mild short stature, a common feature when the genetic cause affects skeletal growth pathways. Radiographic imaging, such as an X-ray, confirms the diagnosis by precisely measuring the lengths of the metacarpals and metatarsals relative to established norms.
Understanding the Genetic Origins
Brachydactyly Type E typically follows an autosomal dominant pattern of inheritance. This means a person only needs to inherit one copy of the altered gene from one parent to develop the condition. The severity of the condition, however, can show variable expressivity, meaning individuals with the same gene mutation can have very different physical presentations.
Specific gene mutations cause BDE, many of which are linked to the Parathyroid Hormone-Related Protein (PTHrP) signaling pathway, which is integral to endochondral bone formation. Mutations in the PTHLH gene are a known cause of BDE, often presenting alongside short stature due to the protein’s role in regulating the growth plate. These mutations disrupt the balance between cartilage cell proliferation and differentiation, leading to premature closure of the growth plates in the affected bones.
Another genetic cause is isolated BDE, which has been linked to mutations in the HOXD13 gene, involved in limb pattern formation. BDE can also occur as a component of more complex genetic syndromes, such as Albright hereditary osteodystrophy (AHO) or pseudohypoparathyroidism (PHP). In these syndromic cases, BDE often results from mutations in the GNAS gene, which encodes a signaling protein downstream of the PTHrP receptor.
Treatment and Long-Term Care
The management of BDE involves a multidisciplinary approach focused on orthopedic function, aesthetic concerns, and monitoring for associated systemic issues. For many individuals, the condition causes no functional limitations, and no intervention is required. When the shortening is significant, particularly in the hands, a consultation with an orthopedic specialist is necessary to assess grip strength and overall hand mechanics.
Surgical intervention is an option for patients seeking improved function or correction of the cosmetic difference. The preferred surgical technique is distraction osteogenesis, or gradual lengthening, which involves cutting the short bone and applying an external fixator device. The fixator is adjusted daily to slowly pull the bone segments apart, promoting the body to generate new bone tissue in the gap, a process called callus distraction.
This lengthening process is performed gradually, often at a rate of approximately 0.5 millimeters per day, and can take several months until the bone fully consolidates. Because the procedure is elective and invasive, it is typically performed in adolescence or early adulthood, with the goal of achieving an average length increase of 15 to 25 millimeters. Psychological support is also important, particularly for adolescents who may experience body image concerns related to the appearance of their hands or feet.
Given the genetic link to the PTHrP-PTHR1 signaling axis, long-term care requires screening and monitoring for potential endocrine or metabolic issues. The involvement of the parathyroid hormone pathway necessitates periodic checks. For those whose BDE is part of a syndromic presentation like PHP, regular monitoring of serum calcium, phosphate, and parathyroid hormone levels is required to manage potential issues like hypocalcemia.