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

  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]

  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]

• 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

  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]

  Recurrent otitis media may lead to conductive hearing impairment or hearing loss. [symptoma.com]

• Skeletal Dysplasia

  The combined use of 3D-CT with ultrasonography is a power tool for the prenatal diagnosis of congenital skeletal dysplasias. [ncbi.nlm.nih.gov]

  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]

  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

  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]

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

• Psychomotor Retardation

  Mild psychomotor retardation is sometimes seen. High levels of keratin sulfate are found in the urine. Genetics Mutations in the COL2A1 gene (12q13.11-q13.2) coding for type II collagen is responsible for this autosomal dominant disorder. [disorders.eyes.arizona.edu]

• 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]

• Round Face

  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

  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 flattening Zygomatic [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]

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]

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]

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]

If you have questions about how your child’s condition and any related health issues may affect your child’s prognosis or long-term goals, talk to your child’s healthcare provider. [chop.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]

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]

We strive 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]

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]

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]

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.