What is the knuckle knuckle dimple knuckle sign?
- Knuckle knuckle dimple knuckle sign is due to the certain pattern of the appearance of the hand.
- This sign is due to the premature closure of the epiphyses.
- Knuckle knuckle dimple knuckle sign is one of the characteristic features of the skeletal abnormalities of Albright’s hereditary osteodystrophy
The “Knuckle-Knuckle-Dimple-Knuckle” sign is a clinical finding that is observed in patients with arthrogryposis, specifically in cases of distal arthrogryposis. Arthrogryposis is a rare condition characterized by multiple joint contractures, limiting the range of motion in affected limbs. Distal arthrogryposis primarily affects the hands and feet, leading to characteristic hand deformities.
Here are some interesting facts about the “Knuckle-Knuckle-Dimple-Knuckle” sign:
- Description: The name “Knuckle-Knuckle-Dimple-Knuckle” describes the appearance of the fingers in a person with distal arthrogryposis. It refers to the following features:
- “Knuckle-Knuckle”: The proximal interphalangeal joint (middle knuckle) and the distal interphalangeal joint (end knuckle) of the affected fingers are prominent and hyperextended.
- “Dimple”: There is a central dimple on the palmar side of the finger, right in the middle between the two knuckles.
- “Knuckle”: The metacarpophalangeal joint (base knuckle) of the finger is flexed and less prominent than the other two knuckles.
- Eponym: The sign is also known as “Carroll’s sign” in honor of Dr. Robert Carroll, who described it in 1969.
- Association with Arthrogryposis: The “Knuckle-Knuckle-Dimple-Knuckle” sign is highly specific for distal arthrogryposis. It is often one of the characteristic features seen in affected individuals.
- Genetic Basis: Distal arthrogryposis is a genetically heterogeneous condition, meaning it can be caused by mutations in different genes. Various types of distal arthrogryposis have been identified, each associated with specific gene mutations.
- Variable Severity: The severity of distal arthrogryposis can vary significantly between individuals. Some may have mild hand deformities, while others may have more severe contractures affecting multiple joints.
- Treatment: Management of distal arthrogryposis involves a multidisciplinary approach, including physical therapy, occupational therapy, and, in some cases, surgical interventions to improve hand function and mobility.
- Rare Condition: Distal arthrogryposis is a relatively rare condition, and its prevalence is estimated to be around 1 in 10,000 to 1 in 3,000 live births.
What is epiphyses?
The longitudinal growth of long bones occurs in the epiphyseal plates at their ends.
After a center of ossification has developed in the epiphysis, a cartilaginous plate, characterized by a typical zonal arrangement is formed.
The cartilaginous plate proliferates using cells from a reservoir at the epiphyseal (i.e. articular) side of the plate.
The cells are orientated to longitudinal rows and become thickened towards the metaphysis.
The extracellular matrix between the hypertrophic chondrocytes becomes calcified and is subsequently replaced in an ossification process by lamellar bone.
Cell proliferation in the epiphyseal plate is regulated by a number of different factors (e.g. IGF-I and BMP-7).
What causes Knuckle knuckle dimple knuckle sign?
The principal cause of Knuckle knuckle dimple knuckle sign is the pseudo hypoparathyroidism type Ia (PHP-1a; autosomal dominant Albright’s hereditary osteodystrophy).
- Patients with pseudo hypoparathyroidism type Ia (PHP-1a; autosomal dominant Albright’s hereditary osteodystrophy) may have a skeletal deformity with a short fourth metacarpal.
- In the ones affected with pseudohypoparathyroidism, the fourth and fifth metacarpal bones are short
- In this condition, when the patient make a fist, the knuckles will have dimples at the fourth and fifth positions, therefore they call it “knuckle, knuckle, dimple, dimple”.
- In other genetic conditions such as Turner syndrome and in Albright syndrome, it’s usually only the fourth metacarpal is short and therefore they call it knuckle, knuckle, dimple, knuckle.
- When they clench their hand to form a fist, a dimple appears where the fourth knuckle should be, emphasizing the short fourth metacarpal bone.
- Short fourth and/or fifth metacarpals present as dimpling over the respective knuckles, which is also called ‘Archibald sign.’
What is the difference between knuckle knuckle dimple knuckle sign and knuckle knuckle dimple dimple sign?
- When the fourth metacarpal is short, it forms the “knuckle knuckle dimple knuckle sign”
- Whereas if both fourth and fifth metacarpals are shortened then that leads to the “knuckle, knuckle, dimple, dimple sign”
- Brachydactyly is one of the commonly recognized signs of Albright’s hereditary osteodystrophy (AHO), along with short adult stature, obesity and developmental delay.
- Short metacarpals are not pathognomonic of AHO and can be seen in many other conditions.
- AHO was first described by Albright and his colleagues in 1942. AHO has been genetically linked to GNAS1 gene.
- Brachydactyly most commonly involves the fourth and fifth metacarpals, but can also be seen in other metacarpals and metatarsals.
- Affected knuckles dimple when the fist is clenched causing the ‘Knuckle–dimple’ sign.
- Patients with AHO features can have either pseudohypoparathyroidism or pseudopseudohypoparathyroidism based on the presence of end-organ resistance to parathyroid hormone.
- These patients have resistance to parathyroid hormone (low calcium, high phosphorous, high parathyroid hormone), short stature, obesity, ectopic calcifications around weight-bearing joints and paraspinal ligaments, and may have cognitive disabilities.
- It is due to a defect in GNAS1 resulting in PTH resistance.
- Patients with pseudo-PHP have similar clinical features to PHP-1a, including a short fourth metacarpal (and metatarsal) bone, but lack PTH resistance.
Albright’s hereditary osteodystrophy
- In 1942 Albright et al’ investigated a patient with seizures, hypocalcaemia, and hyperphosphataemia consistent with a diagnosis of hypoparathyroidism.
- Unexpectedly, repeated injections of bovine parathyroid extract failed to alter the serum calcium or phosphate levels.
- They concluded the patient was resistant to parathyroid hormone (PTH) rather than deficient and coined the term pseudohypoparathyroidism (PHP).
- Additional features, (a short stocky build, round face, cutaneous ossification, and metacarpophalangeal abnormalities) were sufficiently distinctive for two unrelated but phenotypically similar patients with hypocalcaemia to be recalled and shown to have PTH resistance.
- This physical appearance is known as Albright’s hereditary osteodystrophy (AHO).
Most common symptoms of Albright’s hereditary osteodystrophy
Around 80 % to 95% have the below symptoms
- Recurrent joint dislocations
- Abnormal calcium-phosphate regulating hormone level
- Overactive thyroid – Hyperthyroidism
- High blood phosphate levels – Hyperphosphatemia
- Enlarged male breast – Gynecomastia
The symptoms and severity of AHO can vary among individuals, but common features of the condition may include:
- Short Stature: AHO often presents with short stature, meaning individuals with the condition may be shorter than average for their age and gender.
- Skeletal Abnormalities: AHO can cause skeletal abnormalities such as brachydactyly (shortening of the fingers and toes), shortening or bowing of the bones, and abnormal curvature of the spine (scoliosis).
- Obesity: Individuals with AHO may have a tendency to develop obesity, particularly in childhood. This weight gain is often characterized by a central distribution of fat.
- Developmental Delays: Some individuals with AHO may experience delays in reaching developmental milestones, such as delayed motor skills or speech development.
- Cognitive and Behavioral Issues: AHO can be associated with cognitive impairments, including learning difficulties, intellectual disabilities, and behavioral problems.
- Hormonal Abnormalities: AHO can disrupt the normal regulation of various hormones in the body. This can lead to hormone-related symptoms, such as early puberty (precocious puberty) or delayed puberty, hormonal imbalances, and abnormalities in the thyroid or adrenal glands.
- The term Knuckle Knuckle Dimple Knuckle sign refers to a physical examination finding used to assess joint hypermobility, particularly in the fingers. It is also known as the “Walker-Murdoch sign” or the “W-M sign.”
- When performing the Knuckle Knuckle Dimple Knuckle sign, the examiner instructs the patient to bend their fingers at the proximal interphalangeal (PIP) joints while keeping the distal interphalangeal (DIP) joints extended. As the patient flexes the PIP joints, if a visible dimple forms over the dorsum of the hand between the distal knuckles, it is considered a positive sign.
- This sign is indicative of joint hypermobility, specifically excessive movement of the PIP joints, which can cause the skin to tent or form a dimple over the dorsum of the hand. Joint hypermobility is a feature seen in conditions such as Ehlers-Danlos syndrome (EDS) and Marfan syndrome.
- It’s worth noting that the Knuckle Knuckle Dimple Knuckle sign is just one of many clinical signs used to assess joint hypermobility. A comprehensive evaluation by a healthcare professional, including medical history, physical examination, and potentially additional tests, would be necessary for a definitive diagnosis or assessment of joint hypermobility.
The “Knuckle-Knuckle-Dimple-Knuckle” sign is a distinctive feature that can aid in the clinical diagnosis of distal arthrogryposis. However, it is essential to conduct a comprehensive medical evaluation and genetic testing to confirm the diagnosis and provide appropriate management and support for affected individuals and their families.