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Kniest Dysplasia

Kniest dysplasia is a congenital, autosomal dominant disease caused by a COL2A1 gene mutation, characterized by skeletal abnormalities, short stature, and vision and hearing impairment. De novo mutations are also possible, therefore a case may emerge in a family with no history of genetic diseases.


Presentation

Kniest dysplasia may be diagnosed at birth, based on the newborn's clinical traits. Such a child will have short trunk and limbs, up to micromelia or rhizomelia, and abnormally large joints. As the toddler grows older, other aspects become visible, such as the fact that he or she experiences articular pains and restricted movements, as well as the presence of kyphosis, scoliosis or kyphoscoliosis, hyperlordosis, platyspondyly, hypoplastic pelvis, coxa vara, hip dislocation, and clubfoot. Long bones are dumbbell-shaped and have flared metaphysis and flat, squared-off epiphyses. The facies has certain characteristics too, such as a round shape with wide-set eyes, low nasal bridge, micrognathia, and midface retrusion. A cleft palate is not uncommon and, if left untreated, causes speech impairment and delay. The adult height in no more than 106-147 centimeters. Serious discomfort comes from advancing joint enlargement and contracture, especially that of metacarpophalangeal and interphalangeal joints [1].

The disease also causes ocular abnormalities, such as retinopathy, vitreoretinal degeneration, cataract, glaucoma, retinal detachment, myopia. Some of these abnormalities are encountered in the other type II collagenopathies [2]. Recurrent otitis media may lead to conductive hearing impairment or hearing loss. Other features of the disease include the presence of tracheal stenosis, tracheomalacia, blepharoptosis, proptosis, glossoptosis, umbilical or inguinal hernia, and motor delay. Intelligence is unaffected and life expectancy is normal.

Kniest dysplasia diagnosis is difficult to make in a newborn, as some features become apparent only as the child grows older. Other diseases, like Strudwick type dysplasia and allied disorders, or Spranger-Wiedemann disease should be taken into consideration [3] [4].

Recurrent Otitis Media
  • Recurrent otitis media may lead to conductive hearing impairment or hearing loss.[symptoma.com]
  • Recurrent otitis media and hearing loss, both conductive and neurosensory, are frequent. At birth, the limbs are short in relation to the trunk but the proportions change and the trunk becomes comparatively shortened and kyphotic by early childhood.[musculoskeletalkey.com]
Dysmorphic Face
  • A: A dysmorphic face with hypertelorism and a flattened nasal bridge. B, C: Short stature. Height 100.8 cm (-3.42 SD), weight 14.7 kg (-2.82 SD), sitting height 56 cm (-3.17 SD), arm span 103 cm (-2.6 SD). Prominent knees.[raredisorders.imedpub.com]
Underweight
  • She is underweight, with a mild truncal deformity. Radiolographic examination Radiolographic examination at the age of 5 years documented generalised skeletal changes which were consistent with Kniest dysplasia (Figures 3A-3F).[raredisorders.imedpub.com]
Barrel Chest
  • Symptoms of Kniest dysplasia can include: Short limbs Shortened body trunk, making the child appear barrel-chested Scoliosis Hip dysplasia, in which the two hip joints are misaligned or crooked Swollen, stiff or deformed joints that prevent full movement[chop.edu]
  • SYMPTOMS: At birth: Short limbs, barrel-chest, eye problems, joints that do not extend all the way and may be swollen, decreased hearing, cleft palate, and a round mid-face with flat and round facial features.[ksginfo.org]
Blepharoptosis
  • Other ocular findings included cataracts in two patients, dislocated lenses in one patient, and blepharoptosis in one patient.[ncbi.nlm.nih.gov]
  • Other features of the disease include the presence of tracheal stenosis, tracheomalacia, blepharoptosis, proptosis, glossoptosis, umbilical or inguinal hernia, and motor delay. Intelligence is unaffected and life expectancy is normal.[symptoma.com]
  • Dislocated eye lenses, drooping of the eyelids (blepharoptosis), possible blindness with disease of the optic nerve, involvement of the spine or brain, and glaucoma may also occur.[rarediseases.org]
Hearing Impairment
  • Recurrent otitis media may lead to conductive hearing impairment or hearing loss.[symptoma.com]
  • Six of the seven patients had significant hearing impairment and five of the seven patients exhibited clefting abnormalities. One patient had bilateral retinal detachments in his twenties. Six dominant disease-causing COL2A1 variants were detected.[ncbi.nlm.nih.gov]
  • Sight and hearing impairments – such as ottis media, hearing loss, myopia and retinal detachment. Breathing difficulties – usually as a result of a compressed torso.[brighthub.com]
Skeletal Dysplasia
  • Locations & Doctors Nemours is world-renowned for skeletal dysplasia diagnosis and treatment. We strive to maximize children’s mobility, correct deformity, and prevent future complications.[nemours.org]
  • The combined use of 3D-CT with ultrasonography is a power tool for the prenatal diagnosis of congenital skeletal dysplasias.[ncbi.nlm.nih.gov]
  • At Nemours, our goal is to help children with all forms of skeletal dysplasia achieve the highest level of mobility, function and health possible.[nemours.org]
  • Two sibs, one girl and one boy, were observed in infancy with a severe lethal skeletal dysplasia syndrome that radiologically and histologically resembled Kniest dysplasia but clearly differed in clinical course and inheritance.[ncbi.nlm.nih.gov]
  • Abstract Discussion of the skeletal dysplasias caused by genetic mutations in types I and II collagen. Coxa vara in chondrodysplasia: prognosis study of 35 hips in 19 children.[lpamrs.memberclicks.net]
Coxa Vara
  • vara, hip dislocation, and clubfoot.[symptoma.com]
  • Coxa vara in chondrodysplasia: prognosis study of 35 hips in 19 children.[lpamrs.memberclicks.net]
  • vara angle progressive coxa vara symptomatic hip arthritis techniques valgus extension osteotomy may help to decrease an associated hip flexion deformity reconstructive measures may be indicated in patients with subluxation, hinge abduction, or osteoarthritis[orthobullets.com]
Joint Limitation
  • Spinal Fusion for patients with severe kyphoscoliosis Extension Osteotomy to help treat progressive joint limitation Surgical realignment Retinal Detachment repair Myringotomy (surgical procedure to relieve pressure by draining fluid from the eardrum)[en.wikipedia.org]
Shortened Long Tubular Bones
  • What characterizes Kniest dysplasia from other type II Osteochondrodysplasia is the level of severity and the dumb-bell shape of shortened long tubular bones. This condition was first diagnosed by Dr. Wilhelm Kniest in 1952. Dr.[en.wikipedia.org]
Short Neck
  • Manifestations included neonatal respiratory distress, large head, midface hypoplasia, flat nasal bridge, short nose, micrognathia, cleft palate, short neck, micromelia, and mildly bowed limbs.[ncbi.nlm.nih.gov]
  • They may also have craniofacial anomalies such as flat faces, bulging eyes, a short neck and/or cleft palate. Limb deformities such as club foot are also common with Kniest dysplasia.[chop.edu]
  • Other symptoms include a curved spine, instability of the cervical spine at C1 and C2 (vertebras in the neck), short neck, clubfoot, cleft palate, and poorly formed femur heads. Inguinal hernias may also be present.[ksginfo.org]
  • In addition to short limbs, short trunk and short stature, Kniest dysplasia features include flat face, wide forehead and eyes, cleft palate (hole in the roof of the mouth), a rounded short neck, broad chest and dumbbell-shaped bones in the arms and legs[nemours.org]
Abnormal Gait
  • In some cases, affected children may exhibit an unusual “waddling” manner of walking (abnormal gait).[rarediseases.org]

Workup

The diagnosis is made after corroborating the clinical aspect and the radiological traits. These include the presence of deformed and large epiphyses, enlarged metaphyses of the femur, absent femoral head, absent ossification of the pubic bones, broad ilia with hypoplasic basilar areas. The femoral head, when it exists, is affected by delayed ossification and the femoral neck is short and broad. A radiological evaluation will also reveal vertebral abnormalities like platyspondyly or more severe malformations.

If the diagnosis remains unclear, a bone or cartilage biopsy is in order. These will reveal an intensely vacuolated matrix or intracytoplasmic inclusions in chondrocytes.

Genetic studies may reveal COL2A1 gene mutations consisting of deletions [5], splice site mutations [6], or amino acid substitutions [7], leading to the appearance of short type II collagen monomers, the substrate of the disease. Despite being transmitted in an autosomal dominant manner, the disease may manifest as a sporadic disease [8] [9].

Any patient with Kniest dysplasia should be referred for an ophthalmological evaluation. Tests will be performed in order to evaluate the presence of myopia, which is usually high, with a mean of -11 diopters. Retinal detachment is observed in some cases, causing blindness. Dislocated lens, cataract, and vitreoretinal degeneration can also be encountered [1] [10].

Treatment

  • Every child’s condition is different, so treatment is determined on a case-by-case basis.[chop.edu]
  • Because Kniest dysplasia can affect various body systems, treatments can vary between non-surgical and surgical treatment. Patients will be monitored over time, and treatments will be provided based on the complications that arise.[en.wikipedia.org]
  • Locations & Doctors Nemours is world-renowned for skeletal dysplasia diagnosis and treatment. We strive to maximize children’s mobility, correct deformity, and prevent future complications.[nemours.org]
  • Put the very latest scientific and genetic discoveries , diagnostic imaging methods, drug therapies, treatment recommendations, and surgical techniques to work in your practice.[books.google.ro]
  • Treatment Treatment Options: There is no treatment for the dysplasia. Displaced lenses can be removed but the myopia and degenerated vitreous require a cautious approach. Rhegmatogenous detachments demand prompt attention.[disorders.eyes.arizona.edu]

Prognosis

  • Prognosis Prognosis depends on the extent of the joint malformations and vertebral anomalies The documents contained in this web site are presented for information purposes only.[orpha.net]
  • […] premature cleavage of C-propeptide disrupting fibrillogenesis; soft cartilage with vacuolar degeneration of chondrocytes and matrix PROGNOSIS: incapacitation may result from progressive painful, contracted joints TREATMENT: prevent joint contractures[orthopaedicsone.com]
  • Prognosis - Kniest dysplasia Not supplied. Treatment - Kniest dysplasia Not supplied. Resources - Kniest dysplasia Not supplied.[checkorphan.org]
  • Coxa vara in chondrodysplasia: prognosis study of 35 hips in 19 children.[lpamrs.memberclicks.net]
  • […] realignment Retinal Detachment repair Myringotomy (surgical procedure to relieve pressure by draining fluid from the eardrum) Routine monitoring Oxygen support, CPAP, Bipap, Mechanical Ventilation Physical therapy BracingLike treatment options, the prognosis[en.wikipedia.org]

Etiology

  • Recent evidence suggests that the etiology is based on mutations in COL2A1, the gene for collagen type II.[ncbi.nlm.nih.gov]
  • Extensive updates offer you the latest knowledge on etiology, imaging, differential diagnosis, and non-operative and surgical techniques for a wide range of pediatric orthopaedic conditions. "... delivers the most comprehensive text on this subject."[books.google.com]
  • Etiology The disease is caused by mutations in the COL2A1 gene (12q13.11-q13.2) encoding type II collagen.[orpha.net]

Epidemiology

  • Summary Epidemiology Prevalence is unknown. Clinical description The disease is apparent from birth.[orpha.net]
  • Introduction A form of short-trunk dwarfism caused by a defect in the secondary ossification center (epiphysis) Epidemiology rare Pathophysiology caused by abnormal synthesis of Type II collagen primarily affects the vertebrae and epiphysis of bone Genetics[orthobullets.com]
Sex distribution
Age distribution

Pathophysiology

  • Comprehensively updated to reflect everything you need to know regarding retinal diagnosis, treatment, development, structure, function, and pathophysiology, this monumental ophthalmology reference work equips you with expert answers to virtually any[books.google.ro]
  • Introduction A form of short-trunk dwarfism caused by a defect in the secondary ossification center (epiphysis) Epidemiology rare Pathophysiology caused by abnormal synthesis of Type II collagen primarily affects the vertebrae and epiphysis of bone Genetics[orthobullets.com]

Prevention

  • We strive to maximize children’s mobility, correct deformity, and prevent future complications.[nemours.org]
  • The genetic alteration found in this patient suggested that this prevented the normal splicing of COL2A1, resulting in an abnormal type II collagen product.[ncbi.nlm.nih.gov]
  • […] premature cleavage of C-propeptide disrupting fibrillogenesis; soft cartilage with vacuolar degeneration of chondrocytes and matrix PROGNOSIS: incapacitation may result from progressive painful, contracted joints TREATMENT: prevent joint contractures[orthopaedicsone.com]
  • Causes - Kniest dysplasia Prevention - Kniest dysplasia Not supplied. Diagnosis - Kniest dysplasia The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of Kniest dysplasia.[checkorphan.org]

References

Article

  1. Snead MP, McNinch AM, Poulson AV, et al. Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye. 2011;25:1389–1400.
  2. Kannu P, Bateman J, Savarirayan R. Clinical phenotypes associated with type II collagen mutations. J Paediatr Child Health. 2012;48:E38–E43.
  3. Tiller GE, Polumbo PA, Weiss MA, et al. Dominant mutations in the type II collagen gene, COL2A1, produce spondyloepimetaphyseal dysplasia, Strudwick type. Nat Genet.1995;11:87-89.
  4. Spranger J, Winterpracht A, Zabel B. Kniest dysplasia: Dr. W. Kniest and his patient, the molecular defect. Am J Med Genet. 1997;69:79-84.
  5. Winterpacht A, Hilbert M, Schwarze U, et al. Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect. Nature Genet. 1993;3: 323-326.
  6. Spranger J, Menger H, Mundlos S, et al. Kniest dysplasia is caused by dominant collagen TT (COL2A1) mutations: parental somatic mosaicism manifesting as Stickler phenotype and mild spondyloepiphyseal dysplasia. Pediat Radiol. 1994;24: 431-435.
  7. Wilkin D J, Artz A S, South S, et al. Small deletions in the type II collagen triple helix produce Kniest dysplasia. Am J Med Genet. 1999;85:105-112.
  8. Nagendran S, Richards AJ, McNinch A, et al. Somatic mosaicism and the phenotypic expression of COL2A1 mutations. Am J Med Genet A. 2012;158A(5):1204–1207.
  9. Biesecker LG, Spinner NB. A genomic view of mosaicism and human disease. Nat Rev Genet 2013;14:307–320.
  10. Meredith SP, Richards AJ, Bearcroft P, et al. Significant ocular findings are a feature of heritable bone dysplasias resulting from defects in type II collagen. Br J Ophthalmol. 2007;91:1148–1151.

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Last updated: 2019-07-11 21:39