Table 1. [Clinical and Radiographic Features of Type II Collagen Disorders from Most to Least Severe]. - GeneReviews®

Type II Collagen Disorder	Age of Diagnosis	Poor/ Delayed Ossification	Stature	Extraskeletal Abnormalities	Distinguishing Feature(s) ¹
Most severe – often perinatal lethal ²
Achondrogenesis type II	Prenatal	++++++	Extremely short	Flat midface; PRS; hydropic appearance	Often delivered prematurely, stillborn or die shortly after birth (hrs)	Absent or severely retarded ossification of vertebral bodies; short ribs; absent ossification of pubic bones, sacrum, ischial & iliac bones (small w/crescent-shaped inner & inferior margins); very short tubular bones w/delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers
Hypochondro- genesis	Prenatal	+++++	Extremely short	Flat midface; PRS	Majority alive at birth, short survival (days to mos)	Poor/delayed ossification of axial skeleton; very short tubular bones in prenatal period; short ribs; vertebral bodies are small & ovoid, & unossified in cervical region; unossified pubic bones; hypoplastic ilia; short & relatively broad long bones w/delayed ossification in distal femoral & proximal tibial epiphysis
Platyspondylic dysplasia, Torrance type	Prenatal	+++++	Extremely short	Coarse facial features	Majority alive at birth, short survival (days to mos)	Platyspondyly; incomplete vertebral ossification; short ribs & narrow chest; splayed metaphyses of ribs & long bones
Severe to moderately severe – neonatal presentation
Kniest dysplasia	Perinatal	++++	Short	PRS; high prevalence of myopia, lens subluxation, retinal detachment, & other vitreal abnormalities; ↑ risk of tracheo-laryngomalacia	Most severe type II collagen disorder resulting in live birth; long-term joint problems; risk of cervical instability & myelopathy	Platyspondyly w/anterior wedging in low thoracic & lumbar region; coronal cleft vertebral bodies; delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers; dumbbell type deformity long bones (large metaphyses & epiphyses)
SEDC	Perinatal	+++	Short	Flat facial profile, hypertelorism, PRS; ocular abnormalities; ↑ risk of tracheo-laryngomalacia	Severe disproportionate short stature/extremities (˂5th %ile); ↑ risk of cervical instability & spinal cord compression	Delayed/absent ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; delayed carpal & tarsal ossification
SEMD Strudwick type	Perinatal	+++	Short	Flat facial profile, hypertelorism, PRS; ocular abnormalities; ↑ risk of tracheo-laryngomalacia	Severe disproportionate short stature & short extremities (˂5th %ile); ↑ risk of cervical instability & spinal cord compression	Delayed ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; metaphyseal dysplasia in 1st year of life (distinguishing SEMD, Strudwick type from SEDC)
Intermediate – neonatal/child/adult
Spondylo- peripheral dysplasia	Perinatal/ infancy	++	Short	Myopia; hearing loss	Moderate-to-mild disproportionate short stature; short extremities; brachydactyly; occasionally clubfeet	Ovoid vertebra & irregular epiphyses in long bones; brachydactyly type E; short ulnae
SED w/metatarsal shortening	Before adolescence	Normal	Average	Usually no extraskeletal abnormalities	Typical phenotypic hallmark: shortening of 3rd & 4th toes; severe joint pain	Platyspondyly w/irregular endplates; narrowed intervertebral spaces; early osteoarthrosis in spine & lower limb joints (deformed femoral heads & dysplastic pelvis); metatarsal hypoplasia involving postaxial toes
Stickler type 1	Variable (typically perinatal if cleft palate)	Normal	Mild short to average	High risk of high myopia, congenital membranous vitreous abnormalities, retinal detachment, & cataract; U-shaped cleft palate; auditory manifestations	In case of PRS diagnosis most often in infancy	Radiographic appearance of precocious or inflammatory arthritis (childhood)
Mild – adolescent/adult
Mild SED w/premature-onset arthrosis	Adolescence/ adult	Normal	Average	Vision, hearing, & orofacial structures are usually normal.	Progressive joint pain & limitation of motion of the hip & knee joint	Epiphyseal dysplasia & early-onset osteoarthrosis

Type II Collagen
Disorder

Age of
Diagnosis

Poor/
Delayed
Ossification

Stature

Extraskeletal
Abnormalities

Distinguishing Feature(s) ¹

Clinical

Radiographic

Most severe – often perinatal lethal ²

Achondrogenesis
type II

Prenatal

++++++

Extremely
short

Flat midface; PRS; hydropic appearance

Often delivered prematurely, stillborn or die shortly after birth (hrs)

Absent or severely retarded ossification of vertebral bodies; short ribs; absent ossification of pubic bones, sacrum, ischial & iliac bones (small w/crescent-shaped inner & inferior margins); very short tubular bones w/delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers

Hypochondro-
genesis

Prenatal

+++++

Extremely
short

Flat midface; PRS

Majority alive at birth, short survival (days to mos)

Poor/delayed ossification of axial skeleton; very short tubular bones in prenatal period; short ribs; vertebral bodies are small & ovoid, & unossified in cervical region; unossified pubic bones; hypoplastic ilia; short & relatively broad long bones w/delayed ossification in distal femoral & proximal tibial epiphysis

Platyspondylic
dysplasia,
Torrance type

Prenatal

+++++

Extremely
short

Coarse facial features

Majority alive at birth, short survival (days to mos)

Platyspondyly; incomplete vertebral ossification; short ribs & narrow chest; splayed metaphyses of ribs & long bones

Severe to moderately severe – neonatal presentation

Kniest dysplasia

Perinatal

++++

Short

PRS; high prevalence of myopia, lens subluxation, retinal detachment, & other vitreal abnormalities; ↑ risk of tracheo-laryngomalacia

Most severe type II collagen disorder resulting in live birth; long-term joint problems; risk of cervical instability & myelopathy

Platyspondyly w/anterior wedging in low thoracic & lumbar region; coronal cleft vertebral bodies; delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers; dumbbell type deformity long bones (large metaphyses & epiphyses)

SEDC

Perinatal

+++

Short

Flat facial profile, hypertelorism, PRS; ocular abnormalities; ↑ risk of tracheo-laryngomalacia

Severe disproportionate short stature/extremities (˂5th %ile); ↑ risk of cervical instability & spinal cord compression

Delayed/absent ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; delayed carpal & tarsal ossification

SEMD Strudwick type

Perinatal

+++

Short

Flat facial profile, hypertelorism, PRS; ocular abnormalities; ↑ risk of tracheo-laryngomalacia

Severe disproportionate short stature & short extremities (˂5th %ile); ↑ risk of cervical instability & spinal cord compression

Delayed ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; metaphyseal dysplasia in 1st year of life (distinguishing SEMD, Strudwick type from SEDC)

Intermediate – neonatal/child/adult

Spondylo-
peripheral
dysplasia

Perinatal/
infancy

Short

Myopia; hearing loss

Moderate-to-mild disproportionate short stature; short extremities; brachydactyly; occasionally clubfeet

Ovoid vertebra & irregular epiphyses in long bones; brachydactyly type E; short ulnae

SED w/metatarsal shortening

Before
adolescence

Normal

Average

Usually no extraskeletal abnormalities

Typical phenotypic hallmark: shortening of 3rd & 4th toes; severe joint pain

Platyspondyly w/irregular endplates; narrowed intervertebral spaces; early osteoarthrosis in spine & lower limb joints (deformed femoral heads & dysplastic pelvis); metatarsal hypoplasia involving postaxial toes

Stickler type 1

Variable
(typically
perinatal if cleft palate)

Normal

Mild short
to average

High risk of high myopia, congenital membranous vitreous abnormalities, retinal detachment, & cataract; U-shaped cleft palate; auditory manifestations

In case of PRS diagnosis most often in infancy

Radiographic appearance of precocious or inflammatory arthritis (childhood)

Mild – adolescent/adult

Mild SED w/premature-onset arthrosis

Adolescence/
adult

Normal

Average

Vision, hearing, & orofacial structures are usually normal.

Progressive joint pain & limitation of motion of the hip & knee joint

Epiphyseal dysplasia & early-onset osteoarthrosis

From: Type II Collagen Disorders Overview

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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