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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
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 this condition 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).
How common is Albright’s hereditary osteodystrophy?
The data regarding the prevalence of Albright hereditary osteodystrophy is limited.
The closely related disorder, PHP, has a prevalence of 0.34 to 1.1 per 100,000.
However, the prevalence of PHP is estimated to be approximately 1 per 20,000
