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]

• Pallor

  Fundus examination results of the right eye showed prominent vitreousveils, liquefaction, syneresis, and a partial posterior vitreous detachment.Disc pallor was present, with a cup-disc ratio of 0.3. [jamanetwork.com]

• Respiratory Distress

  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]

  distress Breathing difficulties Difficulty breathing [ more ] 0002098 Retinal detachment Detached retina 0000541 Splayed epiphyses Splayed end part of bone 0200003 Tracheomalacia Floppy windpipe 0002779 Umbilical hernia 0001537 Showing of 65 | Last updated [rarediseases.info.nih.gov]

  Birth was at term by emergency caesarean section for fetal distress. She had respiratory distress in the neonatal period but was not ventilated. At birth, she was noted to be short limbed and had bilateral pretibial dimples. [jmg.bmj.com]

  At birth the baby showed severe respiratory distress for four weeks which then resolved. [ojrd.biomedcentral.com]

• 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]

• Respiratory Insufficiency

  […] difficulty due to respiratory insufficiency secondary to thoracic dysplasia problems with vision due to myopia or retinal detachment hip pain due to coxa varus decreased walking distance due to poor muscular endurance and skeletal deformities Physical [orthobullets.com]

  insufficiency OI type III - progressive deforming form This form is characterized as follows: Moderate deformity at birth Development of chest wall deformities Most patients are wheelchair dependent Very short stature Variable sclera Dentinogenesis imperfecta [emedicine.medscape.com]

• 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]

  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]

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

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

• Short Trunk

  Among them is Kniest dysplasia, which is phenotypically variable and includes both skeletal (short trunk and limbs, kyphoscoliosis, prominent joints, and osteoarthritis) and craniofacial characteristics. [ncbi.nlm.nih.gov]

  Kniest dysplasia A rare subtype of collagenopathy (types II and XI) characterised by defective bone growth with short-trunk, short-limb dwarfism, painful enlarged joints leading to arthritis, kyphoscoliosis, lumbar lordosis, flattened vertebral bones [medical-dictionary.thefreedictionary.com]

• Flexion Contracture

  The knee and elbow joints are particularly prominent and enlarged, with limited range of motion; widespread flexion contractures develop. The fingers are relatively long and have bulbous and knobby joints. [musculoskeletalkey.com]

  Systemic examination findings showed abnormal growth with flexion contractures,delayed motor development, hearing loss, muscle atrophy, and normal intelligence.Radiographs showed vertebral defects, short tubular bones with epiphysealirregularities, and [jamanetwork.com]

  0007964 Delayed epiphyseal ossification 0002663 Depressed nasal bridge Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ] 0005280 Enlarged joints 0003037 Flexion [rarediseases.info.nih.gov]

  In addition, flexion contractures were noted in both elbow joints and right hip joint. The baby also had significant hirsutism though there was no cleft palate (Figure 1 and 2). [jpma.org.pk]

  Figure 1 Colour photos of subject KN6 (a) and subject KN2 (b) showing kyphoscoliosis, short trunk, prominent large joins, flexion contractures of hips and fingers, and interphalangeal joint enlargement. [nature.com]

• Coxa Vara

  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]

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

• 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]

  KNIEST SYNDROME Kniest dysplasia is a severe type II collagen disease, characterized by trunk and short limbs, prominent joints and mediastinal hypoplasia (rounded face with flat nasal root). The prevalence is unknown. [issuu.com]

  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].

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]

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

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]

Diagnosis and Prognosis: This is a complex disorder and one of several caused by mutations in the same gene. The diagnosis can be made by an eye doctor but generally a team of specialists is required to distinguish this disease from similar ones. [disorders.eyes.arizona.edu]

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]

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]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.ro]

Summary Epidemiology Prevalence is unknown. Clinical description The disease is apparent from birth. [orpha.net]

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]

We strive to maximize children’s mobility, correct deformity, and prevent future complications. [nemours.org]

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]

[…] 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]

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.