Rare Pulmonology News

Disease Profile

Limb-mammary syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

LMS; Mammary hypoplasia, ectrodactyly, and other hand/foot anomalies

Categories

Congenital and Genetic Diseases; Eye diseases; Female Reproductive Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 69085

Definition
Limb-mammary syndrome (LMS) is a rare disease belonging to the group of ectodermal dysplasias.

Epidemiology
Less than 50 cases have been described in the literature so far.

Clinical description
Clinically, the syndrome is characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Clinical expression is extremely variable. Individuals with mild LMS have isolated athelia. All three major categories of limb defects (i.e., deficiencies, duplications, and fusion/separation defects), as well as several combinations of these anomalies, were observed. Variation in the severity of the limb defects may be observed, not only between individuals but also between the left and right hand/foot of one individual. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia (absence of one or more teeth), earpits and cleft palate with or without bifid uvula. Skin and hair are spared.

Etiology
LMS is caused by loss-of-function mutations in exon 13 and 14 of the TP63 gene localized to the subtelomeric region of chromosome 3 (3q27). There is a strong genotypephenotype correlation in syndromes caused by mutations in this gene, which is also responsible for several other ectodermal dysplasia syndromes (ectrodactyly-ectodermal dysplasiacleft lip palate (EEC), and the Hay-Wells, Rapp-Hodgkin and ADULT syndromes) and some cases of split hand-foot syndrome.

Differential diagnosis
Differential diagnosis should include ulnar-mammary syndrome, an autosomal dominant condition caused by mutations in the TBX3 gene and characterised by ulnar ray defects or post-axial polydactyly, anal atresia, genito-urinary abnormalities, hypohidrosis and breast hypoplasia.

Genetic counseling
LMS is an autosomal dominant disease.

Management and treatment
Treatment of LMS depends on the anomalies present. Surgical intervention may be offered for correction of the hand/foot deformities in order to improve function and reduce physical disfigurement.

Prognosis
The prognosis for LMS patients is good and life expectancy is normal.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Absent lacrimal punctum
0001092
Absent nipple
Absent nipples
0002561
Bilateral breast hypoplasia
Two underdeveloped breasts
0012814
Breast aplasia
Absent breast
0100783
Hypoplastic nipples
Small nipples
0002557
Lacrimal duct atresia
Unopened tear duct
0000564
5%-29% of people have these symptoms
3-4 finger cutaneous syndactyly
0011939
Bifid uvula
0000193
Blepharitis
Inflammation of eyelids
0000498
Chronic irritative conjunctivitis
0007717
Cleft hard palate
0410005
Cleft lip
0410030
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Dry skin
0000958
Hypodontia
Failure of development of between one and six teeth
0000668
Hypohidrosis
Decreased ability to sweat
Decreased sweating
Sweating, decreased

[ more ]

0000966
Nail dysplasia
Atypical nail growth
0002164
Oligodactyly
0012165
Submucous cleft soft palate
0011819
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770
1%-4% of people have these symptoms
Alopecia
Hair loss
0001596
Aplasia of the ovary
Absent ovary
0010463
Aplasia of the uterus
Absent uterus
uterus absent

[ more ]

0000151
Freckling
0001480
Malar flattening
Zygomatic flattening
0000272
Multiple cafe-au-lait spots
0007565
Primary amenorrhea
0000786
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Psoriasiform dermatitis
0003765
Sparse eyebrow
Sparse eyebrows
0045075
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Camptodactyly
Permanent flexion of the finger or toe
0012385
Hallux valgus
Bunion
0001822
Joint contracture of the hand
0009473
Split foot
Lobster-claw foot deformity
Split-foot

[ more ]

0001839
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
Syndactyly
Webbed fingers or toes
0001159

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Limb-mammary syndrome. Click on the link to view a sample search on this topic.