Limb–mammary syndrome

Alternate names

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

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.

Cause

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 genotype-phenotype correlation in syndromes caused by mutations in this gene, which is also responsible for several other ectodermal dysplasia syndromes (ectrodactyly-ectodermal dysplasia-cleft lip palate (EEC), and the Hay-Wells, Rapp-Hodgkin and ADULT syndromes) and some cases of split hand-foot syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

LMS is an autosomal dominant disease.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Absent lacrimal punctum
• Absent nipple(Absent nipples)
• Bilateral breast hypoplasia(Two underdeveloped breasts)
• Breast aplasia(Absent breast)
• Hypoplastic nipples(Small nipples)
• Lacrimal duct atresia(Unopened tear duct)

5%-29% of people have these symptoms

• 3-4 finger cutaneous syndactyly
• Bifid uvula
• Blepharitis(Inflammation of eyelids)
• Chronic irritative conjunctivitis
• Cleft hard palate
• Cleft lip
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Dry skin
• Hypodontia(Failure of development of between one and six teeth)
• Hypohidrosis(Decreased ability to sweat)
• Nail dysplasia(Atypical nail growth)
• Oligodactyly
• Submucous cleft soft palate
• Toe syndactyly(Fused toes)

1%-4% of people have these symptoms

• Alopecia(Hair loss)
• Aplasia of the ovary(Absent ovary)
• Aplasia of the uterus(Absent uterus)
• Freckling
• Malar flattening(Zygomatic flattening)
• Multiple cafe-au-lait spots
• Primary amenorrhea
• Protruding ear(Prominent ear)
• Psoriasiform dermatitis
• Sparse eyebrow(Sparse eyebrows)

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.

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.

NIH genetic and rare disease info

• NIH info on Limb–mammary syndrome

Limb–mammary syndrome is a rare disease.

Limb–mammary syndrome Resources
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