Paula and Bobby
Parents of Lillie
Arthrogryposis, Distal, Type 3; DA3
What is Arthrogryposis, Distal, Type 3; DA3?
Arthrogryposis, Distal, Type 3; DA3 is a rare disease. It is also known as Arthrogryposis Multiplex Congenita, Distal, Type Iia Camptodactyly, Cleft Palate, And Clubfoot DA3 Distal arthrogryposis type 3 Gordon Syndrome.
Gordon syndrome (distal arthrogryposis type 3) is an autosomal dominant disorder characterized by contractures of upper and lower limbs. It is distinguishable from other types of distal arthrogryposis by cleft palate and short stature. Gordon syndrome is caused by heterozygous mutations in the PIEZO2 gene. Different mutations of this gene also cause distal arthrogryposis type 5 and MardenþWalker syndrome.
The most characteristic features of this autosomal dominant syndrome with variable expression and reduced penetrance are camptodactyly, involving the fingers and toes (the thumbs may be be spared), club feet and a cleft palate. Some of the males have undescended testes. There is some suggestion that an omphalocele, vertebral anomalies and cutaneous syndactyly might be features of the condition. Spinal abnormalities reported in one case (Robinow and Johnson, 1981) consisted of stenosis of the spinal canal and a lack of the normal cephalo-caudal widening of the interpedicular distances. Short stature might be a part of this syndrome. Intelligence is usually normal and there might be a characteristic facial appearance with down-slanting palpebral fissures, best seen in the paper by Robinow and Johnson (1981).
Ioan et al., (1993) reported a further family where 13 members were affected in four generations. However, none of these individuals had cleft palate. The authors emphasise that there appears to be reduced penetrance in females in this condition.
Courtens et al., (1997) reported a boy who died at the age of 31 months. He had a cleft palate, camptodactyly, kyphoscoliosis, and hypotonia. His mother had been treated for a cleft palate. Both mother and child had early onset hearing loss.
Becker and Splitt (2001) reported a family where a mother and two children had cleft palate and distal joint contractures, consistent with a diagnosis of Gordon syndrome. In a third pregnancy, a fetus was identified with a posterior fossa cyst, consistent with a Dandy-Walker variant. Ultrasound also showed micrognathia, unilateral talipes and fixed extension of all the fingers. The facies is this family were very similar to those reported by Robinow and Johnson (1981) as cases of Gordon syndrome.
Mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) have now been found (McMillin et al., 2014). These authors found mutations in the same gene in distal arthrogryposis type 5, and in Marden-Walker syndrome.
McMillin et al. (2014) reported on identification of heterozygous PIEZO2 mutations in 83% of families with Gordon syndrome. In addition, the authors found mutations 82% of families with distal arthrogryposis type 5 and one of two families with MardenþWalker syndrome. The presence of cleft palate was significantly associated with c.8057G>A mutation.
Alisch et al. (2016) described a family with three affected individuals carrying PIEZO2 mutations. The patients showed multiple contractures (metacarpo-phalangeal and interphalangeal joints, elbow, shoulder, knee, and ankle joints), clubfeet, short stature, bifid uvula/cleft palate, and a distinct facial phenotype including ptosis. Additional features were mild intellectual disability and psychomotor developmental delay.
* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]
What gene changes cause Arthrogryposis, Distal, Type 3; DA3?
The syndrome is inherited in the following inheritance pattern/s:
Autosomal Dominant - In the case of autosomal dominant inheritance, just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation that occurs during the reproductive process.
OMIM Number - 114300 (please check the OMIM page for updated information)
The syndrome can be caused by mutations in the following gene/s location/s:
PIEZO2 - 18p11.22-p11.21
What are the main symptoms of Arthrogryposis, Distal, Type 3; DA3?
The typical symptoms of the syndrome are:
Micrognathia, Pectus excavatum, Knee flexion contracture, Kyphoscoliosis, Lumbar hyperlordosis, Camptodactyly of finger, Ptosis, Down-sloping shoulders, Talipes equinovarus, Talipes, Scoliosis, Thoracolumbar scoliosis, Distal arthrogryposis, Finger syndactyly, Facial asymmetry, Epicanthus, Decreased hip abduction, Limitation of joint mobility, Congenital hip dislocation, Cleft palate, Clinodactyly of the 5th finger, Cutaneous finger syndactyly, Cryptorchidism, Arthrogryposis multiplex congenita, Short stature, Hearing impairment, High palate, Short phalanx of finger, Autosomal dominant inheritance, Ophthalmoplegia, Short neck, Submucous cleft hard palate, Ulnar deviation of the hand or of fingers of the hand, Single transverse palmar crease, Overlapping toe, Bifid uvula, Camptodactyly of toe, Abnormality of the rib cage, Skeletal muscle atrophy
How does someone get tested for Arthrogryposis, Distal, Type 3; DA3?
The initial testing for Arthrogryposis, Distal, Type 3; DA3 can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
What is FDNA Telehealth?
FDNA Telehealth is a leading digital health company that provides faster access to accurate genetic analysis.
With a hospital technology recommended by leading geneticists, our unique platform connects patients with genetic experts to answer their most pressing questions and clarify any concerns they may have about their symptoms.
Benefits of FDNA Telehealth
Our platform is currently used by over 70% of geneticists and has been used to diagnose over 250,000 patients worldwide.
FDNA Telehealth provides facial analysis and screening in minutes, followed by fast access to genetic counselors and geneticists.
Ease of Use
Our seamless process begins with an initial online diagnosis by a genetic counselor and follows by consultations with geneticists and genetic testing.
Accuracy & Precision
Advanced artificial intelligence (AI) capabilities and technology with a 90% accuracy rate for a more accurate genetic analysis.
Faster access to genetic counselors, geneticists, genetic testing, and a diagnosis. As fast as within 24 hours if required. Save time and money.
Privacy & Security
We guarantee the utmost protection of all images and patient information. Your data is always safe, secure, and encrypted.