The clinical presentation of Dyggve-Melchior-Clausen syndrome (DMC), initially described approximately 50 years ago [1], is distinguished by a combination of several features that develop in early childhood [1] [2] [3] [4] [5] [6]:

• Skeletal changes - The most prominent feature of DMC syndrome is a very short stature, with standard deviation scores (SDS) reaching as low as -12.6 SD in some reports [1]. The upper part of the body seems to be more severely affected and a pigeon-shaped (or barrel) chest is one of the hallmarks of Dyggve-Melchior-Clausen syndrome [1]. Rhizomelic limb shortening is an accompanying feature [1] [3]. Lumbar lordosis, brachydactyly, and broad interphalangeal joints are seen in up to 100% of patients, whereas scoliosis, kyphosis, protrusion of the sternal bone, genu valgum or varum, and limited joint extension are other notable manifestations that develop in up to 50% of individuals [1] [6].
• Mental retardation - The second crucial feature of DMC syndrome is mental retardation, varying from moderate to severe [1].
• Craniofacial changes - Virtually all patients who suffer from DMC syndrome develop microcephaly and a disproportionate development of the skull and facial bones compared to the brain size [1] [5]. In addition, characteristic facial changes include a narrow forehead, thick lips, macrognathia, prominent ears, and macrostomia [1].

Other notable findings are a protruded abdomen and generalized hirsutism [1].

• Disproportionate Short Stature

  It is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature, microcephaly, and coarse facies. [ncbi.nlm.nih.gov]

  Normally, there is growth deficiency resulting in short stature. [rarediseases.info.nih.gov]

  Disproportionate short stature usually occurs after 18 months. Additional features may include a long skull, distinctive facial appearance, a protruding jaw, microcephaly, and claw-like hands. [rareguru.com]

  DMC syndrome may be suspected following a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings (e.g., barrel chest, and disproportionate short stature). [hellodoktor.com]

• Barrel Chest

  Last reviewed 01/2018 This dysplastic syndrome is characterised by: short stature short trunk barrel chest accentuated lumbar lordosis restricted joint mobility waddling gait in some families this condition has been associated with mental retardation. [gpnotebook.com]

  Diagnosis Clinically, thoracic deformities in the form of barrel chest become visible in the first 18 months of life. [accesspediatrics.mhmedical.com]

  This site is intended for healthcare professionals General Practice Notebook This dysplastic syndrome is characterised by: short stature short trunk barrel chest accentuated lumbar lordosis restricted joint mobility waddling gait in some families this [gpnotebook.co.uk]

• Cough

  In infancy and childhood she suf- fered measles, whooping cough, repeated upper respiratory infections and undernourish- ment. [dev.docslide.net]

• Failure to Thrive

  NM_017653.6:c.302G>A Homozygous Autosomal, Recessive Maddirevula et al. 2018 223801.16 Egypt Female Yes Yes Failure to thrive; Profound global devel... [cags.org.ae]

• Arthritis

  Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. ‏ [books.google.com]

  Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. ‎ [books.google.de]

  Kandziora F,, Mittlmeier T, & Kerschbaumer F: Stage-related surgery for cervical spine instability in rheumatoid arthritis. [thejns.org]

  Arthritis and decreased joint mobility often develop early in life.People with spondyloepiphyseal dysplasia congenita have mild changes in their facial features. The cheekbones close to the nose may appear flattened. [icdlist.com]

  Arthritis Rheumatol. 2015 Jan 7. [Epub ahead of print] 3. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial. [mhlw.go.jp]

• Fracture

  Gallie WE: Fractures and dislocation of the cervical spine. Am J Surg 46:495–499, 1939 Gallie WE: Fractures and dislocation of the cervical spine. Am J Surg 46:495–499, 1939 Search Google Scholar Export Citation 17. [thejns.org]

  Abnormalities 422 Carpal Abnormalities 429 Thumb Abnormalities 437 Acroosteolyses 446 Chapter 7 455 Tarsal Abnormalities 466 Chapter 8 473 Abnormalities of Joint Position 489 Premature Degenerative Joint Disease 496 Osteosclerosis Hyperostosis 510 Multiple Fractures [books.google.es]

  Kozlowski spondylometaphyseal dysplasia) Weaver syndrome Specific symptoms depend on the particular condition, but symptoms may include: Spinal deformities like scoliosis, kyphosis or lordosis Cervical spine instability Hip and joint deformities Bone fractures [chop.edu]

  Subluxation of the hip or dislocated femoral heads 8/15 53 Kyphosis 8/15 53 Small deep sacrosciatic notch 6/15 40 Thick calvaria 4/15 26 Osteoporosis 4/15 26 Others: Increased intracranial digital markings 2/15 13 Odontoid hypoplasia 2/15 13 Healed fracture [ncbi.nlm.nih.gov]

• Short Neck

  short stature, disproportionate (short trunk) Chest Ribs Sternum Clavicles And Scapulae: sternal protrusion Head And Neck Neck: short neck Skeletal Limbs: genu valgum hypoplastic distal ulna narrow joint spaces Skeletal Pelvis: coxa vara short femoral [malacards.org]

  Difficult tracheal intubation is likely (even without atlantoaxial instability) because of the presence of a short neck, prominent, big jaws, macroglossia, and limited mouth opening. [accessanesthesiology.mhmedical.com]

  […] femoral neck Short neck of thighbone 0100864 Short metacarpal Shortened long bone of hand 0010049 Short metatarsal Short long bone of foot 0010743 Spondyloepimetaphyseal dysplasia 0002651 Thickened calvaria Increased thickness of skull cap Thickened [rarediseases.info.nih.gov]

  For the management of the patient, difficult airway due to short neck, macroglossia, and the disturbance of neck flexion was described. [bioline.org.br]

• Coarse Face

  Clinical description Clinically, Dyggve-Melchior-Clausen disease (DMC) is characterized by progressive dwarfism with short trunk, protruding sternum, rhizomelic limb shortening, postnatal microcephaly with facial dysmorphism, coarse face and intellectual [orpha.net]

  The common clinical features are short stature, microcephaly, intellectual disability, and coarse face. [karger.com]

  prognathism coarse face Neurologic Central Nervous System: normal intelligence Chest External Features: barrel chest Skeletal Skull: calvarial thickening (parietal and occipital area) marked pneumatization of paranasal sinuses Clinical features from [malacards.org]

• Waddling Gait

  Waddling gait was present. His skeletal age was 6 years. An increased anteroposterior chest diameter and kyphoscoliosis was present, and proximal portions of the upper and lower limbs were short. [indianpediatrics.net]

  Last reviewed 01/2018 This dysplastic syndrome is characterised by: short stature short trunk barrel chest accentuated lumbar lordosis restricted joint mobility waddling gait in some families this condition has been associated with mental retardation. [gpnotebook.com]

  gait, and radiographic findings of irregular iliac crests and flattening of vertebral bodies; autosomal recessive inheritance. [medical-dictionary.thefreedictionary.com]

Because Dyggve-Melchior-Clausen syndrome is very rare, the diagnosis may be difficult to attain without a thorough diagnostic workup. Since affected children develop the typical clinical presentation in the first several years of life, the physician should first obtain a detailed patient history from the parents. The history should cover the onset of symptoms and their progression, as well as severity. The fact that many identified patients either come from consanguineous marriages or have first-degree relatives who already suffer from Dyggve-Melchior-Clausen syndrome makes a complete family history crucial for identifying a genetic background of the disease. As soon as clinical suspicion is raised, imaging studies should be employed. Plain radiography of the axial skeleton, the pelvis, and the limbs is the key step for determining the exact type of deformity [1] [3]. One of the most specific findings seen in this syndrome is the lace-like character of the iliac crests. Small iliac wings, bilateral hip dislocation, a widened pubic symphysis, acetabular hypoplasia, a wide sacroiliac joint and deformed femoral heads are other prominent findings in the hips in these patients [1] [3]. A barrel-shaped chest with broad ribs, platyspondyly, and a double-hump shape of the bone end-plates provide sufficient evidence to make a solid diagnosis of Dyggve-Melchior-Clausen syndrome [1] [3]. Genetic studies can be used as a definitive method, which confirm mutations of the dymeclin gene located on chromosome 18 [1] [2] [4] [5] [6].

Full text links Group 7SearchHeart failure treatmentPapersTopicsCollectionsEffects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter [read.qxmd.com]

Dym-mutant cells display multiple defects in vesicle traffic, as evidenced by enhanced dispersal of Golgi markers in interphase cells, delayed Golgi reassembly after brefeldin A treatment, delayed retrograde traffic of an endoplasmic reticulum-targeted [agris.fao.org]

Decisions about use of a new treatment, or about a change in your current treatment plan, should be in consultation with your doctor or other healthcare professional. [healthetreatment.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

There is a good prognosis for general health and survival. The radiographic lacy appearance of iliac crests and generalized platyspondyly with double-humped end plates are pathognomonic of DMC. [jocr.co.in]

Initial clinical presentation may be similar, but the intellectual prognosis is different. [mendeley.com]

However, due to the poor quality of osseous tissue, minimal-invasive surgery such as guided growth may be preferable Prognosis The disease often progresses towards orthopedic complications which can include lumbar lordosis, thoracic kyphosis, hip luxation [orpha.net]

Abnormalities, Multiple* / etiology, physiopathology Bone Diseases, Developmental* / etiology, physiopathology Diagnosis, Differential Dwarfism / etiology, physiopathology Endoplasmic Reticulum, Rough / metabolism Genes, Recessive Humans Mental Retardation* Prognosis [biomedsearch.com]

Export Citation: APA/MLA Format Download EndNote Download BibTex MeSH Terms Descriptor/Qualifier: Abnormalities, Multiple* / etiology, physiopathology Bone Diseases, Developmental* / etiology, physiopathology Diagnosis, Differential Dwarfism / etiology [biomedsearch.com]

As the etiology of the disorder is unknown, we have used a positional cloning strategy to identify the DMC gene. We detected seven deleterious mutations within a gene predicted from a human transcript (FLJ20071) in 10 DMC families. [ncbi.nlm.nih.gov]

Etiology The disease is caused by mutations of the DYM gene (18q21.1). The large majority of mutations identified in the gene predict a loss of function of its product. [orpha.net]

Elsevier Health Sciences, ١٨‏/٠٨‏/٢٠١٣ - 979 من الصفحات Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders [books.google.com]

Recombinant growth hormone (rGH) therapy may be employed to improve stature based on the underlying etiology and growth velocity. [researchwithrutgers.com]

Summary Epidemiology To date approximately 100 cases have been reported worldwide. [orpha.net]

Pathophysiology Electron microscopy of chondrocytes shows dilated cisternae of rough endoplasmic reticulum, containing fine granular or amorphous material. [accesspediatrics.mhmedical.com]

Atlantoaxial instability-induced spinal cord compression is a serious and preventable complication. The purpose of this report is to describe the first case of… Figures from this paper 13 Citations Dyggve-Melchior-Clausen syndrome V. GuptaA. KohliV. [semanticscholar.org]

Atlantoaxial instability-induced spinal cord compression is a serious and preventable complication. [ncbi.nlm.nih.gov]

Preventive or corrective orthopedic surgery may be an option to manage lower limb deformities. [orpha.net]

Thereby, we used a guided growth technique, aiming to prevent further deterioration (Figure 6 [Fig. 6]). [egms.de]

1. Aglan MS, Temtamy SA, Fateen E, Ashour AM, Eldeeb K, Hosny GA. Dyggve–Melchior–Clausen syndrome: clinical, genetic, and radiological study of 15 Egyptian patients from nine unrelated families. J Child Orthop. 2009;3(6):451-458.
2. Dyggve HV, Melchior JC, Clausen J. Morquio-Ullrich’s disease: an inborn error of metabolism? Arch Dis Child. 1962;37:525–534.
3. Beighton P. Dyggve–Melchior–Clausen syndrome. J Med Genet. 1990;27:512–515.
4. Thauvin-Robinet C, El Ghouzzi V, Chemaitilly W, et al. Homozygosity mapping of a Dyggve–Melchior–Clausen syndrome gene to chromosome 18q21.1. J Med Genet. 2002;39:714–717.
5. Ehtesham N, Cantor RM, King LM, et al. Evidence that Smith–McCort dysplasia and Dyggve–Melchior–Clausen dysplasia are allelic disorders that result from mutations in a gene on chromosome 18q12. Am J Hum Genet. 2002;71:947–951.
6. Gupta V, Kohli A, Dewan. Dyggve melchior clausen syndrome. Indian Pediatr. 2010;47(11):973-975.