Lethal Types of

Skeletal
Dysplasia

Introduction
Lethal skeletal dysplasia, Torrance
type is a severe disorder of bone growth.
People with this condition have very
short arms and legs, underdeveloped
pelvic bones, and unusually short fingers
and toes (brachydactyly)

 Lethal
skeletal
dysplasias
(LSD's)form
a
heterogeneous group which are commonly characterized
being non survivable for prolonged periods ex-utero.
They include:
achondrogenesis
atelosteogenesis
campomelic dysplasia
chondrodysplasia punctata: lethal variants
metatropic dysplasia: lethal variants
Pacman dysplasia
perinatal lethal hypophosphatasia: primarily a metabolic
abnormality but has major skeletal manifestations
osteogenesis imperfectatype II:2ndcommonestlethal
skeletal dysplasia
thanatophoric dysplasia:commonestlethal
skeletal
dysplasia
short rib polydactyly syndromes(SRPS)

Achondrogenesis
Epidemiology
The estimated incidence is 1:40,000 with no
recognized gender predilection.
Pathology
It is classified as anosteochondrodysplasias, meaning
deficiency ofboth bone and cartilage development.
Subtypes
There are several recognized sub types:
type I
type Ia:Houston-Harris sub type
type Ib:Parenti-Fraccaro sub type

type II:Langer-Saldino achondrogenesis

Antenatal ultrasound
Sonographic diagnosis may be possible after 13 weeks
where nuchal oedema may be evident as an early
(although non specific) sign.
The fetal bony structures are often unable to be identified.
There may also be extreme micromelia. Calvarial
ossification can be preserved with the type II sub type
which can in turn give afloating headappearence.
Additional sonographic findings include:
micrognathia
narrow fetal thorax
rib fractures can be present in type Ia
disproportionately small body compared with head
Other ancilliary sonographic features that may be present
include
polyhydramnios
development ofhydrops fetalis

Achondrogenesis

Atelosteogenesis
Type 1
a disorder that affects the development of bones throughout the
body
Affected individuals are born with inward- and upward-turning feet
(clubfeet) and dislocations of the hips, knees, and elbows. Bones
in the spine, rib cage, pelvis, and limbs may be underdeveloped or
in some cases absent
Characteristic facial features include a prominent forehead, wideset eyes (hypertelorism), an upturned nose with a grooved tip, a
very small lower jaw and chin (micrognathia), an opening in the
roof of the mouth (a cleft palate). Males with this condition can
have undescended testes
typically have an underdeveloped rib cage that affects the
development and functioning of the lungs.

Type 2
a severe disorder of cartilage and bone development. Infants
born with this condition have very short arms and legs, a narrow
chest, and a prominent, rounded abdomen
unusually positioned thumbs (hitchhiker thumbs).
Type 3
Their hands and feet are wide, with broad fingers and toes that
may be permanently bent (camptodactyly) or fused together
(syndactyly)
People with atelosteogenesis type 3 who survive past the
newborn period may have learning disabilities and delayed
language skills, which are probably caused by low levels of
oxygen in the brain due to respiratory problems. As a result of
their

orthopedic

abnormalities,

they

also

have

delayed

development of motor skills such as standing and walking

Camptomelic Dwarfism
frequently associated a number
of non-skeletal abnormalities
including: hydrocephalus,
hydronephrosis, congenital
heart disease
Antenatal ultrasound
Findings include:
lower extremity bowing,
femoral/tibial bowing, reduced
chest circumference,
narrow fetal thorax, hypoplastic

Chondrodysplasia
Punctata
collective name for a heterogenous group of skeletal
dysplasias.Calcific stippling of cartilage and periarticular soft tissues is often a common feature.
Subtypes
It can be broadly divided into rhizomelicand nonrhizomelic forms:
rhizomelic chondrodysplasia punctata(RCDP)
X-linked dominant chondrodysplasia punctata (CDPX2)

non-rhizomelic chondrodysplasia punctata(NCRDP)

brachytelephalangic chondrodysplasia punctata (CDPX1)
Conradi-Hnermann syndrome

Metatrophic Dysplasia
Metatrophic

dysplasiais

rare

group

of

skeletal dysplasia.This group includes

fibrochondrogenesis
lethal metatropic dysplasia(type

2)

or

hyperchondrogenesis
lethal hyperplastic metatropic dysplasia(type 1)
Schneckenbecken dysplasia
There

can

be

marked

metaphyses of the bones.

enlargement

of

the

Pacman Dysplasia
This syndrome is characterized by epiphyseal stippling and
osteoclastic overactivity.
It is characterized radiographically by severe stippling of the
lower spine and long bones, and periosteal cloaking. Patients also
have short metacarpals.
The syndrome may be inherited as an autosomal recessive trait.
This disorder should be included in the differential diagnosis of
mucolipidosis type II.
In order to make a definitive diagnosis, lysosomal storage should
be investigated by electron microscopy, or enzyme assays should
be performed. Familial recurrence can be easily detected by
prenatal ultrasonography.

Perinatal
Hypophosphatasia

lethal

Markers
carriers may have low levels of serum alkaline phophatase
(ALP)
fetal ALP isoenzymes are often low on chorionic villus
sampling
urine phosphoethanolamine iselevated
Skeletal
Patients with this type tend to haveshort limb dwarfism
(micromelia)with verysoft calvaria.
blue sclerae
spurs(Bowdler spurs)in the mid-portion of the forearms
and lower legs
unusually dense, round, flattened, butterfly shaped; and
sagittally clefted vertebral bodies
variability in femoral shape including "chromosome" like,
"campomelic" like, and shortening with or without
metaphyseal cupping or irregularities

 general underossification of the bones of the fetus

limb shortening
lack of ossification of groups of vertebral bodies: may
sometimes give a pattern of three ossified and three
unossified vertebral bodies
lack of ossification of the neural arches of the spine
lack of ossification of the hands
marked demineralisation of the fetal calvarium and
absent segments of the spine
osteochondral projections of the midshaft of the fibula
and ulna
bifid diaphyses
polyhydramnioson ultrasound

Osteogenesis
Imperfecta
heterogeneous group of congenital, non-sex-linked,
genetic
disorders
of
collagen
type
I
production,involving connective tissues and bones.
osteoporosis and fragile bones that fracture easily, as
well as, blue sclera, dental fragility, and hearing loss.
There is extreme variation in clinical symptoms
based on genetic basis and subtypes.Osteogenesis
imperfecta affects both bone quality and quantity
(i.e. bone mass).
Three main types are easily distinguished
mild: type I
perinatal lethal: type II
progressive deforming: type III
Types IV to VIII are variable in severity and
uncommon

teogenesis type IIA. Shortened femur (8 mm) with multiple fractures.

steogenesis type IIA. Stippled ribs, indicating multiple fractures

Thanatophoric
Dysplasia
There are two recognised subtypes.
type I:marked underdevelopment of skeleton,
telephone handle femurs more pronounced.
type II
the presence of acloverleaf skullmay be a
distinctive feature
limb shortening milder and bowing is not a feature 3

Associations
polyhydramnios4

Short rib polydactyly

syndrome
a rare group of severe osteochondrodysplasias. There
are four major recognised types present:
type I:Saldino-Noonan type
type II::Majewski type
type III:Verma-Naumoff type
type IV:Beemer-Langer type
short-limb dysplasia/micromelia
narrow fetal thorax(with short ribs)
polydactyly
congenital cardiac anomalies
congenital renal anomalies