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Mandibuloacral dysplasia with type B lipodystrophy(MADB)

MedGen UID:
332940
Concept ID:
C1837756
Disease or Syndrome
Synonyms: Lipodystrophy, type B, associated with mandibuloacral dysplasia; MADB
SNOMED CT: Mandibuloacral dysostosis co-occurrent with type B lipodystrophy (1003432003); Mandibuloacral dysplasia with type B lipodystrophy (1003432003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ZMPSTE24 (1p34.2)
 
Monarch Initiative: MONDO:0012074
OMIM®: 608612
Orphanet: ORPHA90154

Definition

Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370). [from OMIM]

Additional description

From MedlinePlus Genetics
A common feature of mandibuloacral dysplasia is a lack of fatty tissue under the skin (lipodystrophy) in certain regions of the body. The two types of this disorder, mandibuloacral dysplasia with type A lipodystrophy (MADA) and mandibuloacral dysplasia with type B lipodystrophy (MADB) are distinguished by the pattern of fat distribution throughout the body. Type A is described as partial lipodystrophy; affected individuals have a loss of fatty tissue from the torso and limbs, but it may build up around the neck and shoulders. Type B is a generalized lipodystrophy, with loss of fatty tissue in the face, torso, and limbs.

MADA usually begins in adulthood, although children can be affected. MADB begins earlier, often just after birth. Many babies with MADB are born prematurely.

People with mandibuloacral dysplasia can have mottled or patchy skin pigmentation or other skin abnormalities. Some people with this condition have features of premature aging (a condition called progeria), such as thin skin, loss of teeth, loss of hair, and a beaked nose. Some individuals with mandibuloacral dysplasia have metabolic problems, such as diabetes.

Mandibuloacral dysplasia is a condition that causes a variety of abnormalities involving bone development, skin coloring (pigmentation), and fat distribution. People with this condition may grow slowly after birth. Most affected individuals are born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), leading to the characteristic features of a small chin and sloped shoulders. Other bone problems include loss of bone from the tips of the fingers (acroosteolysis), which causes bulbous finger tips; delayed closure of certain skull bones; and joint deformities (contractures).  https://medlineplus.gov/genetics/condition/mandibuloacral-dysplasia

Clinical features

From HPO
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Osteolytic defects of the distal phalanges of the hand
MedGen UID:
341480
Concept ID:
C1849547
Finding
Acroosteolysis of distal phalanges (feet)
MedGen UID:
871254
Concept ID:
C4025739
Anatomical Abnormality
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Loss of truncal subcutaneous adipose tissue
MedGen UID:
331962
Concept ID:
C1835384
Finding
Loss (reduction of previously present) of subcutaneous adipose tissue in the region of the trunk.
Progressive clavicular acroosteolysis
MedGen UID:
324869
Concept ID:
C1837757
Finding
Progressive bone resorption in the distal part of the clavicle.
Decreased adipose tissue around neck
MedGen UID:
325247
Concept ID:
C1837763
Finding
Reduced amount of adipose tissue in the region of the neck.
Loss of subcutaneous adipose tissue in limbs
MedGen UID:
325248
Concept ID:
C1837764
Finding
Loss (disappearance) of previously present subcutaneous fat tissue in arm or leg.
Loss of facial adipose tissue
MedGen UID:
325251
Concept ID:
C1837767
Finding
Loss of normal subcutaneous fat tissue in the face.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Generalized lipodystrophy
MedGen UID:
1369615
Concept ID:
C4317112
Disease or Syndrome
Generalized degenerative changes of the fat tissue.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Hyperlipidemia
MedGen UID:
5692
Concept ID:
C0020473
Disease or Syndrome
An elevated lipid concentration in the blood.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Insulin-resistant diabetes mellitus
MedGen UID:
163439
Concept ID:
C0854110
Disease or Syndrome
A type of diabetes mellitus related not to lack of insulin but rather to lack of response to insulin on the part of the target tissues of insulin such as muscle, fat, and liver cells. This type of diabetes is typically associated with increases both in blood glucose concentrations as well as in fasting and postprandial serum insulin levels.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Premature loss of teeth
MedGen UID:
66678
Concept ID:
C0232513
Finding
Exfoliation of a tooth more than 2 SD earlier than the normal age for the deciduous teeth and not related to traume or neglect. Exfoliation of a permanent tooth is per se abnormal.
Hypoplasia of teeth
MedGen UID:
852449
Concept ID:
C0235357
Congenital Abnormality
Developmental hypoplasia of teeth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Abnormality of the neck
MedGen UID:
540042
Concept ID:
C0266623
Congenital Abnormality
An abnormality of the neck.
Bird-like facies
MedGen UID:
325243
Concept ID:
C1837758
Finding
Narrow nasal ridge
MedGen UID:
373404
Concept ID:
C1837761
Finding
Decreased width of the nasal ridge.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Dermal atrophy
MedGen UID:
101793
Concept ID:
C0151514
Disease or Syndrome
Partial or complete wasting (atrophy) of the skin.
Brittle hair
MedGen UID:
120480
Concept ID:
C0263490
Disease or Syndrome
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Mottled pigmentation
MedGen UID:
163653
Concept ID:
C0860439
Finding
Patchy and irregular skin pigmentation.
Prominent superficial veins
MedGen UID:
324870
Concept ID:
C1837785
Finding
A condition in which superficial veins (i.e., veins just under the skin) are more conspicuous or noticable than normal.
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
An increased concentration of insulin in the blood.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMandibuloacral dysplasia with type B lipodystrophy
Follow this link to review classifications for Mandibuloacral dysplasia with type B lipodystrophy in Orphanet.

Professional guidelines

PubMed

Hitzert MM, van der Crabben SN, Baldewsingh G, van Amstel HKP, van den Wijngaard A, van Ravenswaaij-Arts CMA, Zijlmans CWR
Orphanet J Rare Dis 2019 Dec 19;14(1):294. doi: 10.1186/s13023-019-1269-0. PMID: 31856865Free PMC Article

Recent clinical studies

Diagnosis

Hitzert MM, van der Crabben SN, Baldewsingh G, van Amstel HKP, van den Wijngaard A, van Ravenswaaij-Arts CMA, Zijlmans CWR
Orphanet J Rare Dis 2019 Dec 19;14(1):294. doi: 10.1186/s13023-019-1269-0. PMID: 31856865Free PMC Article
Alarcón PI, Mujica I, Sanz P, García CJ, Gilgenkrantz S
Am J Med Genet A 2019 Jun;179(6):893-895. Epub 2019 Mar 28 doi: 10.1002/ajmg.a.61139. PMID: 30919593
Haye D, Dridi H, Levy J, Lambert V, Lambert M, Agha M, Adjimi F, Kohlhase J, Lipsker D, Verloes A
Am J Med Genet A 2016 Oct;170(10):2750-5. Epub 2016 Jul 13 doi: 10.1002/ajmg.a.37825. PMID: 27410998
Kwan JM
JAMA Dermatol 2015 May;151(5):561-2. doi: 10.1001/jamadermatol.2014.5068. PMID: 25629449
Slimani S, Megateli I, Ladjouze-Rezig A
Joint Bone Spine 2014 May;81(3):263. Epub 2014 May 1 doi: 10.1016/j.jbspin.2013.09.009. PMID: 24793088

Clinical prediction guides

Hitzert MM, van der Crabben SN, Baldewsingh G, van Amstel HKP, van den Wijngaard A, van Ravenswaaij-Arts CMA, Zijlmans CWR
Orphanet J Rare Dis 2019 Dec 19;14(1):294. doi: 10.1186/s13023-019-1269-0. PMID: 31856865Free PMC Article
Haye D, Dridi H, Levy J, Lambert V, Lambert M, Agha M, Adjimi F, Kohlhase J, Lipsker D, Verloes A
Am J Med Genet A 2016 Oct;170(10):2750-5. Epub 2016 Jul 13 doi: 10.1002/ajmg.a.37825. PMID: 27410998

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