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Dyggve-Melchior-Clausen Syndrome

Dyggve Melchior Clausen Disease

Dyggve-Melchior-Clausen syndrome is a very rare genetic disorder that is characterized by a childhood-onset of mental retardation, microcephaly, various facial changes, and a range of skeletal abnormalities that affect the trunk, the spine, and the limbs. An autosomal recessive pattern of inheritance is established and the majority of patients have affected siblings or first-degree relatives. The diagnosis can be made through a physical examination, a patient history, and plain X-rays of the skeleton.


Presentation

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].

Developmental Disabilities
  • Intellectual disability is a common neuropsychiatric developmental disability reported in patients of Dyggve-Melchior-Clausen syndrome. [1] , [2] In an association study on Japanese population, it was found that the gene (Dymeclin gene) responsible for[ijpm.info]
Asymptomatic
  • We report two siblings with classical clinical and radiological features of DMC and asymptomatic atlanto-axial dislocation. A novel homozygous splice-site mutation (IVS15 3G T) was detected.[ncbi.nlm.nih.gov]
Barrel Chest
  • 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. Rhizomelic limb shortening is an accompanying feature.[symptoma.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]
  • Clinically, thoracic deformities in the form of barrel chest become visible in the first 18 months of life.[accessanesthesiology.mhmedical.com]
Macrostomia
  • In addition, characteristic facial changes include a narrow forehead, thick lips, macrognathia, prominent ears, and macrostomia. Other notable findings are a protruded abdomen and generalized hirsutism.[symptoma.com]
Normal Hearing
  • Noteworthy features of normal hearing, normal teeth and a normal odontoid with no subsequent atlanto-axial instability, but microcephaly and mental sub-normality were notable in our present patient.[egms.de]
Atlanto-Axial Instability
  • The most notable radiographic findings are a lacy iliac crest apophysis, hip dysplasia, double vertebral hump, and odontoid hypoplasia with atlanto-axial instability.[ncbi.nlm.nih.gov]
  • Noteworthy features of normal hearing, normal teeth and a normal odontoid with no subsequent atlanto-axial instability, but microcephaly and mental sub-normality were notable in our present patient.[egms.de]
Hirsutism
  • Other notable findings are a protruded abdomen and generalized hirsutism. Because Dyggve-Melchior-Clausen syndrome is very rare, the diagnosis may be difficult to attain without a thorough diagnostic workup.[symptoma.com]
Grandiose Ideas
  • ideas, inflated self-esteem with impairment of judgment, and insight.[ijpm.info]
Short Neck
  • neck Decreased length of neck 0000470 Sloping forehead Inclined forehead Receding forehead [ more ] 0000340 Spinal canal stenosis Narrow spinal canal 0003416 5%-29% of people have these symptoms Attention deficit hyperactivity disorder Attention deficit[rarediseases.info.nih.gov]
  • 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]
  • neck Spondyloepimetaphyseal dysplasia Thoracic kyphosis Waddling gait Wide pubic symphysis Based on the frequency of symptoms observed, the following information may be noted: Very frequently present symptoms in 80-99% of the cases: Abnormality of epiphysis[dovemed.com]
  • He had a short neck, short trunk, flared nibs with a bulging sternum, and a thonacic kyphosis with dorsal lordosis. The large joints were enlarged. There was no hepatosplenomegaly and no genu valgum.[healthdocbox.com]
Thick Lips
  • In addition, characteristic facial changes include a narrow forehead, thick lips, macrognathia, prominent ears, and macrostomia. Other notable findings are a protruded abdomen and generalized hirsutism.[symptoma.com]
Narrow Forehead
  • In addition, characteristic facial changes include a narrow forehead, thick lips, macrognathia, prominent ears, and macrostomia. Other notable findings are a protruded abdomen and generalized hirsutism.[symptoma.com]
Waddling Gait
  • gait, and radiographic findings of irregular iliac crests and flattening of vertebral bodies; autosomal recessive inheritance.[medical-dictionary.thefreedictionary.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]
Behavior Problem
  • So, the clinician should be cautious enough to understand the psychopathology of behavioral problems in the background of intellectual disability.[ijpm.info]
Irritability
  • […] being referred from a tertiary care hospital, with the history of delayed developmental milestones, inability to carry out activities of daily living on his own, inability to read, write, or calculate since birth, along with increased talkativeness, irritability[ijpm.info]

Workup

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].

Treatment

  • 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]
  • Hello Health Group does not provide medical advice, diagnosis or treatment.[hellodoktor.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[ncbi.nlm.nih.gov]

Prognosis

  • Initial clinical presentation may be similar, but the intellectual prognosis is different.[mendeley.com]
  • 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]
  • Prognosis The disease often progresses towards orthopedic complications which can include lumbar lordosis, thoracic kyphosis, hip luxation, deformation of the knees and spinal cord compression secondary to instability of the atlas-axis.[orpha.net]
  • Genetic testing can also confirm a diagnosis. [1] Last updated: 5/16/2011 What is the prognosis of Dyggve-Melchior-Clausen syndrome? DMC syndrome is a progressive condition, meaning that signs and symptoms worsen over time.[rarediseases.info.nih.gov]

Etiology

  • 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]
  • 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]
  • 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]

Epidemiology

  • Summary Epidemiology To date around 100 cases have been recorded. Clinical description Clinically, DMC is characterized by progressive dwarfism with short trunk, protruding sternum, microcephaly and mental retardation of varying severity.[orpha.net]
Sex distribution
Age distribution

Prevention

  • Atlantoaxial instability-induced spinal cord compression is a serious and preventable complication.[ncbi.nlm.nih.gov]
  • Currently, Dyggve-Melchior-Clausen Syndrome may not be preventable, since it is a genetic disorder.[dovemed.com]
  • Next Document: Prevention and treatment of the side effects of cancer chemotherapy[biomedsearch.com]
  • Atlantoaxial instability— induced spinal cord compression is a serious and preventable complication.[thejns.org]
  • Proximal femoral osteotomies should be avoided to prevent rendering hip arthroplasty difficult at the adult age.[em-consulte.com]

References

Article

  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.

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Last updated: 2019-07-11 20:06