Dysplasias: spondylo-epi-metaphyseal

(Spondyloepiphyseal dysplasia, Rolland - Desbuquois dysplasia, Wolcott-Rallisson syndrome, Dyggve-Melchior-Clausen syndrome)Heterogeneous group of rare disorders, characterized by the association of vertebral , epiphyseal and metaphyseal anomalies. An international classification recognizes at least 18 different entities (see table). The usual clinical presentation is that of a small (non-harmonious) disproportionate stature. The most frequent forms are the pseudoachondroplasia, the Strudwick type, Morquiosyndrome (mucopolysaccharidosis type IV) and Dyggve-Melchior-Clausen syndrome (see these topics).

spondylo-meta-epiphyseal dysplasia Strudwick type: mutation in the gene COL2A1 on 12q13. At birth: short trunk and limbs; small chest with short ribs and protruding abdomen; hypertelorism, flat face and cleft palate. Severe myopia with risk of retinal detachment. Lumbar hyperlordosis appears gradually. Cervical kyphosis due to hypoplasia of C3 or hypoplasia of the odontoid process. Normal intelligence. Impaired respiratory function.
Spondylo-meta-epiphyseal dysplasia type aggrecan: ACHAN gene (15q26) mutation. Very short stature (< 1 m) with relative macrocephaly, midface hypoplasia and slight prognathism. Short neck, barrel chest. rhizomely and brachydactyly (broad thumbs, interdigital webs). Platyspondyly and vertebral clefts. Early osteoarthritis.
spondylo-meta-epiphyseal dysplasia with joint hyperlaxity (type Beighton) also known as progeroid type I Ehlers Danlos syndrome (see this term): at birth, short stature and laxity of the joints: dislocation of hip (25%) and the head of the radius. Kyphoscoliosis rapidly progressive (sometimes paraplegia and cor pulmonale during childhood). Oval face with protruding eyes. Cleft palate or arched palate in 50% of cases. Hyperelastic skin. Cardiac abnormalities of type ASD or VSD. Frequent mental retardation
dyssegmentar Rolland-Desbuquois dysplasia: segmental anomalies of the vertebrae (platyspondyly, fissured vertebrae), including cervical with limitation of the extension of the neck. Small chest with pulmonary hypoplasia, cleft palate. Short and curved limbs. Mental retardation. Frequent lung infections. Death in childhood from pulmonary complications.
spondylo-meta-epiphyseal dysplasia with multiple dislocations (type Hall): marked hypotonia at birth. Facial dysmorphism: hypoplasia of midface, depressed nasal bridge. In 30% of cases: tracheomalacia or laryngeal stenosis. Moderate scoliosis. Lack of fusion of the sacral vertebrae.
spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcification: at birth, it is especially the shortening of limbs which is striking. Narrow chest. Facial dysmorphism: broad forehead, protruding eyes, hypoplasia of midface, hypertelorism, micrognathia. Risk of spinal cord compression due to hypoplasia of the odontoid process and ligamentous laxity with subluxation of C1/C2. Progressive kyphoscoliosis with respiratory failure and chronic cor pulmonale.
spondylo-meta-epiphyseal dysplasia type Iraqi (type Sohat): short stature at birth with short limbs and short neck. Protruding abdomen with hepatosplenomegaly. Vertebral anomalies and lumbar lordosis, platyspondyly. Hyperlaxity.
spondylo-meta-epiphyseal dysplasia type Paria (Venezuela): short stature and short limbs: diagnosis by the age of 5 years. Difficulties for walking. Early osteoporosis and osteoarthritis.
SPONASTRIME dysplasia: acronym for SPOndylar NAsal abnormalities and STRIation of MEtaphyses. Short stature at birth. Big head with a short nose with the a depressed ensellure, hypoplasia of midface. Kyphoscoliosis and progressive hyperlordosis. Vara Caxa, femoral head necrosis. Cases of laryngeal stenosis and tracheobronchomalacie have been reported.

Type	transmission	MIM	gene	locus	features
Strudwick	A dominant	184 250	COL2A1	12q13	myopia, deafness
pseudoachondroplasie	A dominant	177 170	COMP	19p13.1
Missouri	A dominant	602 111	MMP13	11q22.3
Dyggve-Melchior-Clausen	A recessive	223 800	DYM	18q12	mental retardation
Smith-McCort	A recessive	607 326	DYM	18q12
Menger or anauxetic	A recessive	607 095	RMRP	9p21-p12	hypodontia, mental retardation, ice-axe-shaped feet
Wolkott-Rallison	A recessive	226 980	EIF2AK3	2p12	diabetes, mental retardation
matriline	A recessive	678 728	MATN3	2p23
Schimke ( immuno-osseous dysplasia)	A recessive	242 900	SMARCAL1	2q34	hypothyroidy, renal failure
Pakistani type or brachyolmia	A recessive	603 005	PAPSS2	10q22
oman	A recessive	608 637	CHST3	10q22.1
aggrecan type	A recessive	612 813	ACAN	15q26.1	macrocephaly, early arthrosis
Morquio type A	A recessive	253 000	GALNS	16q24.3	see topic
Morquio type B	A recessive	253 010	GLBI	3p21.33
dyssegmentar dysplasia Silverman-Handmaker	A recessive	224 410	perlecan	1 p36.1	encephalocele, lethal
dyssegmentar dysplasia Rolland-Desbuquois	A recessive	224 400	?	?	cleft palate
Handigodu	?	-	?	?	India
with articular laxity or leptodactylic Hall	A dominant	603 546	KIFF22	16p11.2	multiple luxations
Maroteaux or pseudoMorquio type II	A dominant	184 095	?	?
dysplasia metatropic	?	156 530 250 600	?	?
progressive with mental retardation	A recessive	-	?	?
SPONASTRIME dysplasia	A recessive	271 510	?	?
Irapa (SEMDIT)	A recessive	271 650	?	?	Mexico
with articular laxity Beighton type	A recessive	271 640	B3GALT6	1p36.33	hyperlaxity, cleft palate
Sohat or iraki	A recessive ?	602 557	?	?	hepatosplenomegaly
short limbs and abnormal calcification	A recessive	271 665	?	?
micromelic or Kozlowsky	?	601 096	?	?
X-linked	X	300 106	?	?
X-linked with mental retardation	X	300 232	?	?
opsismodysplasia	A recessive	258 480	INPPL1	11q13.4	rhizomelic micromelia , wide fontanels

Anesthetic implications:

check the stability of the atlas-axis joint because there is a major risk of spinal cord compression; short stature: careful selection of the diameter of the endotracheal tube and risk of bronchial intubation; facial dysmorphism (hypoplasia of midface and/or micrognathia): risk of difficult intubation: the use of laryngeal mask may be ineffective; abnormal vertebrae, which can make a neuraxial block technically difficult to achieve; risk of narrow lumbar canal?; possible mental retardation; poor ventilatory function

EXPERT CONSENSUS for MANAGEMENT:

Surgical morbi-mortality is higher than in the normal population and the risk of anesthetic complications is very high: these patients must therefore be managed in facilities where care of those complications can be taken.

It is why�:

- a full neurological examination is necessary before general or locoregional anesthesia

- imaging (MRI or CTscan) of the full spine is recommended

- a flexion/extension MRI of the cervical spine is necessary if there is any concern about its stability

- polysomnography, respiratory functional tests (restrictive or obstructive syndrome) and cardiac evaluation (echocardiography) must be considered before an anesthesia

- morphological and functional anomalies of the upper airway, a decrease in mobility of the cervical spine and bronchial airway anomalies increase the morbidity and mortality of anesthesia

- a sedative premedication can be administered before anesthesia

- for intubation, a videolaryngoscope and a intubating fiberscope must be immediately available

- tracheostomy can be extremely difficult in those patients, particularly in emergency; it is crucial to identify the position of the cricothyroid membrane (XRays, echography) before anesthesia

- extubation must be preferably done in the operating room; if this may not be the case, an experienced team must be present

- in patients in whom a fragility of the spinal cord is suspected (concept of spinal cord at risk : significant cyphosis, risk of hypotension, long lasting surgery, difficult surgical positioning), neurological monitoring must be done during the whole procedure, and it is better to avoid epidural anesthesia

Reference:
White KK, Bompadre V, Goldberg MJ, Bober MB, Cho T-J et al.
Best practices in peri-operative management of patients with skeletal dysplasias.
Am J Med Genet 2017�; 173A�: 2584-95

References :

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Gyggve-Melchior-Clausen syndrome.
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- Szmuk P, Matuszceak M, Carlson RF, Warters RD, Rabb MF, Ezri T.
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Anesthetic management in a child with Rolland-Desbuquois type dyssegmental dysplasia.
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Updated: December 2017