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].

• Dysmorphic Face

  Our affected girl had dysmorphic and radiographic features consistent with Kniest disease: cleft palate, hip dysplasia, dysmorphic flat face, short trunk and extremities, spine deformity, platyspondyly, short and broad femoral necks. [raredisorders.imedpub.com]

  Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe “boomerang dysplasia”?. Ann Genet 1992; 35 : 129–133. 33. Cormier-Daire V, Savarirayan R, Unger S, Rimoin DL, Lachman RS. [nature.com]

• 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]

  otitis media Recurrent middle ear infection 0000403 Respiratory distress Breathing difficulties Difficulty breathing [ more ] 0002098 Retinal detachment Detached retina 0000541 Splayed epiphyses Splayed end part of bone 0200003 Tracheomalacia Floppy [rarediseases.info.nih.gov]

• Barrel Chest

  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]

  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]

• 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]

  Interventions to monitor and treat visual impairments, hearing loss and osteoarthritis. [brighthub.com]

  impairment Deafness Hearing defect [ more ] 0000365 Hypoplasia of the odontoid process 0003311 Lattice retinal degeneration 0007992 Platyspondyly Flattened vertebrae 0000926 Rhegmatogenous retinal detachment 0012230 Short long bone Long bone shortening [rarediseases.info.nih.gov]

  impairment (subject KN2, KN3, KN5, KN6, KN7, and KN8 8 ). [nature.com]

• Coxa Vara

  vara, hip dislocation, and clubfoot. [symptoma.com]

  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]

  Coxa vara in chondrodysplasia: prognosis study of 35 hips in 19 children. [lpamrs.memberclicks.net]

• 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]

  Note short-limbed dysplasia, large head, short neck, narrow thorax, short and small fingers, and bowed extremities. [emedicine.medscape.com]

  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]

  Considered one of several forms of dwarfism, babies with Kniest dysplasia are born with a short trunk and shortened arms and legs. They may also have craniofacial anomalies such as flat faces, bulging eyes, a short neck and/or cleft palate. [chop.edu]

• Round Face

  Kniest dysplasia is a severe type II collagenopathy characterized by a short trunk and limbs, prominent joints and midface hypoplasia (round face with a flat nasal root). [monarchinitiative.org]

  face Circular face Round facial appearance Round facial shape [ more ] 0000311 30%-79% of people have these symptoms Abnormality of the epiphysis of the femoral head Abnormality of the end part of the innermost thighbone 0010574 Aplasia/hypoplasia of [rarediseases.info.nih.gov]

• Abnormal Gait

  […] disturbance Abnormal gait Abnormal walk Impaired gait [ more ] 0001288 Hip contracture 0003273 Hip dislocation Dislocated hips Dislocation of hip [ more ] 0002827 Hypoplastic pelvis 0008839 Inguinal hernia 0000023 Lumbar kyphoscoliosis 0004619 Malar [rarediseases.info.nih.gov]

  In some cases, affected children may exhibit an unusual “waddling” manner of walking (abnormal gait). [rarediseases.org]

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].

Every child’s condition is different, so treatment is determined on a case-by-case basis. [chop.edu]

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]

Once we’ve identified your child’s condition, we work together to create a personalized treatment plan. Treatment is led by our world-renowned pediatric orthopedic experts, including Dr. William Mackenzie. [nemours.org]

Treatment[edit] Because Kniest dysplasia can affect various body systems, treatments can vary between non-surgical and surgical treatment. [en.wikipedia.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]

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]

1 answer Kniest Dysplasia synonyms 1 answer Kniest Dysplasia prognosis 1 answer What is Kniest Dysplasia 1 answer Which advice would you give to someone who has just been diagnosed with Kniest Dysplasia? 1 answer [diseasemaps.org]

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]

This observation further supports the conclusion that SPD and PLSD-T are not two etiologically distinct entities but belong to the same continuum phenotypic spectrum. [ojrd.biomedcentral.com]

Bailey suggested two groups in addition to SED congenita and SED tarda: pseudo-Morquio disease and pseudoachondroplasia SED. [9] In this article, only the most common types of SED (ie, SED congenita and SED tarda) are discussed in detail. [10] Etiology [emedicine.medscape.com]

Chapters on epidemiology, embryology, non-syndromic hearing loss, and syndromic forms of hearing loss have all been updated with particular attention to the vast amount of new information on molecular mechanisms, and chapters on clinical and molecular [books.google.com]

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]

Epidemiology International statistics SED congenita is a rare genetic disorder. The prevalence is approximately 3.4 per million population. [7] The incidence rate is approximately 1 per 100,000 live births. [emedicine.medscape.com]

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]

Spranger and Langer provided a further review of 29 patients in 1970. [2] In 1969, Fraser noted the particular association of SED with myopia, retinal detachment, and deafness. [3] In 1939, Jacobsen recognized SED tarda in a report of 20 patients. [4] Pathophysiology [emedicine.medscape.com]

Physiology and pathophysiology of the growth plate. Birth Defects Res C Embryo Today 2003; 69 : 123–143. 5. Ballock RT, O'Keefe RJ. The biology of the growth plate. J Bone Joint Surg Am 2003; 85 : 715–726. 6. [nature.com]

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]

At Nemours, we work as a team to maximize children’s mobility, correct deformity and prevent future complications. [nemours.org]

[…] 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]

Stiffness of the metacarpophalangeal and interphalangeal joints prevents the patient from making a complete fist. Precocious osteoarthritis develops and may become incapacitating by late childhood. [musculoskeletalkey.com]

It was obvious that, in order to discover the causes of congenital malformations and cast strategies for their prevention, it would be necessary to have knowledge of the baseline of their frequency, and that this required uniformity of definition of terms [books.google.ro]

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.