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]

• 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 Short neck Decreased length of neck 0000470 Splayed epiphyses Splayed end part of bone 0200003 Umbilical hernia 0001537 Showing of 53 Last updated: 5/1/2019 Making a diagnosis for a genetic or rare [rarediseases.info.nih.gov]

• 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]

  impairment Deafness Hearing defect [ more ] 0000365 Hip dislocation Dislocated hips Dislocation of hip [ more ] 0002827 Proptosis Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ] 0000520 Retinal detachment Detached [rarediseases.info.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

  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

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

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

  vara 0002812 Hearing impairment Deafness Hearing defect [ more ] 0000365 Hip dislocation Dislocated hips Dislocation of hip [ more ] 0002827 Proptosis Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ] 0000520 Retinal [rarediseases.info.nih.gov]

  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]

• 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]

  neck Decreased length of neck 0000470 Splayed epiphyses Splayed end part of bone 0200003 Umbilical hernia 0001537 Showing of 53 Last updated: 5/1/2019 Making a diagnosis for a genetic or rare disease can often be challenging. [rarediseases.info.nih.gov]

• Round Face

  face Circular face Round facial appearance Round facial shape [ more ] 0000311 5%-29% of people have these symptoms Cataract Clouding of the lens of the eye Cloudy lens [ more ] 0000518 Ectopia lentis 0001083 Glaucoma 0000501 Glossoptosis Retraction [rarediseases.info.nih.gov]

• Abnormal Gait

  gait Abnormal walk Impaired gait [ more ] 0001288 Hip contracture 0003273 Inguinal hernia 0000023 Lumbar kyphoscoliosis 0004619 Malar flattening Zygomatic flattening 0000272 Motor delay 0001270 Recurrent otitis media Recurrent middle ear infection 0000403 [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].

• Shortened Long Bone

  The fetus had an abnormal spine, shortened long bones and a left clubfoot. After running postmortem tests and ultrasound, the researchers believed that the fetus suffered from hypochondrogenesis. [en.wikipedia.org]

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.