Am J Med Genet A. 2011 Jul; 155A(7): 1716-20
Chacon-Camacho OF, Vázquez J, Zenteno JC

Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, hypertrichosis, intellectual disability, and absence and/or hypoplasia of the nails or terminal phalanges of the hands and feet. The syndromic features of ZLS are highly variable and can overlap with other entities featuring gingival fibrosis. This study describes a patient with ZLS with novel findings, including colpocephaly, hemivertebra, polydactyly, hyperpigmentation, and hemihyperplasia. Thus, the present report expands the phenotypic spectrum of this uncommon syndrome.

Genet Couns. 2011; 22(1): 1-10
Davalos IP, Brambila-Tapia AJ, Dávalos NO, Durán-González J, González-Mercado MG, Cruz-Ramos JA, Ríos-González BE, E'vega R, Zavala-Cerna MG, García-Cruz MO, García-cruz D

Gingival fibromatosis can be present as an isolated form or be part of a genetic disease. The Zimmermann-Laband syndrome (ZLS) is a rare disorder inherited as an autosomal dominant fashion, clinically characterized by gingival fibromatosis, bulbous soft nose, thick floppy ears, nail dysplasia, joint hyperextensibility, hepatosplenomegaly, skeletal anomalies and occasional mental retardation. We studied a girl aged five years with clinical and radiological features of the ZLS, additionally she presented deafness not previously described in the ZLS, as only partial hearing loss was reported in some patients. The father presented some facial features suggestive of ZLS, nevertheless he did not have gingival fibromatosis or hypertrichosis. We suggest that this case supports that ZLS can be part a contiguous genes syndrome or be consequence ofa gene mutation with wide variable expression. The present report supports that ZLS has a wide clinical spectrum.

Int J Oral Maxillofac Surg. 2010 Sep; 39(9): 937-41
Lin Z, Wang T, Sun G, Huang X

Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, abnormalities of the nose and/or ears, absence and/or hyperplasia of the nails or terminal phalanges of the hands and feet, hyperextensibility of joints, hepatosplenomegaly, mild hirsutism and mental retardation. The syndromic characteristics of Zimmermann-Laband syndrome are highly variable and complicated. This paper described a patient with Zimmermann-Laband syndrome with new manifestations and discusses the possible underlying genetic mechanisms.

Clin Dysmorphol. 2010 Jan; 19(1): 48-50
Balasubramanian M, Parker MJ

Clin Dysmorphol. 2009 Oct; 18(4): 205-8
Douzgou S, Mingarelli R, Dallapiccola B

We report on a patient with congenital generalized hypertrichosis, mental retardation, tonic-clonic seizures with onset during the first year of life and gingival overgrowth, unrelated to antiepileptic treatment. This phenotype represents a unique combination of features, bridging the variable association of gingival overgrowth, generalized hypertrichosis, mental retardation or epilepsy. This may occur in combination with nail and/or digital anomalies, as in Zimmermann-Laband syndrome, and the broader phenotypes of the Anavi, Göhlich-Ratmann and Ramon syndromes. On the basis of the clinical overlap between our patient and these disorders inherited either as autosomal dominant or recessive traits and unknown molecular defects, a recurrence risk of one in four was considered appropriate.

Clin Dysmorphol. 2008 Jul; 17(3): 181-5
Abo-Dalo B, Roes M, Canún S, Delatycki M, Gillessen-Kaesbach G, Hrytsiuk I, Jung C, Kerr B, Mowat D, Seemanova E, Steiner CE, Stewart H, Thierry P, van Buggenhout G, White S, Zenker M, Kutsche K

Am J Med Genet A. 2007 Nov 15; 143A(22): 2668-74
Abo-Dalo B, Kim HG, Roes M, Stefanova M, Higgins A, Shen Y, Mundlos S, Quade BJ, Gusella JF, Kutsche K

Zimmermann-Laband syndrome (ZLS) is a rare autosomal dominant inherited disorder characterized by a coarse facial appearance, gingival fibromatosis, and absence or hypoplasia of the terminal phalanges and nails of hands and feet. Additional, more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism, and mental retardation. Mapping of the translocation breakpoints of t(3;8) and t(3;17) found in patients with the typical clinical features of ZLS defined a common breakpoint region of approximately 280 kb located in 3p14.3, which includes the genes CACNA2D3 and WNT5A. Breakpoint cloning revealed that both translocations most likely occurred by non-homologous (illegitimate) recombination. Mutation analysis of nine genes located in 3p21.1-p14.3, including CACNA2D3, which is directly disrupted by one breakpoint of the t(3;17), identified no pathogenic mutation in eight sporadic patients with ZLS. Southern hybridization analysis and multiplex ligation-dependent probe amplification (MLPA) did not detect submicroscopic deletion or duplication in either CACNA2D3 or WNT5A in ZLS-affected individuals. Mutation analysis of nine conserved nongenic sequence elements (CNEs) in 3p21.1-p14.3, which were identified by interspecies comparison and may represent putative regulatory elements for spatiotemporally correct expression of nearby genes, did not show any sequence alteration associated with ZLS. Taken together, the lack of a specific coding-sequence lesion in the common region, defined by two translocation breakpoints, in sporadic patients with ZLS and an apparently normal karyotype suggests that either some other type of genetic defect in this vicinity or an alteration elsewhere in the genome could be responsible for ZLS.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Apr; 103(4): 521-7
Haytac MC, Ozcelik O

Hereditary gingival fibromatosis (HGF) is characterized by the slowly progressive fibrous enlargement of gingival tissue. It usually develops as an isolated disorder but can also be one feature of various syndromes. The currently preferred terminology of these syndromes mainly describes the clinical features of the disorder without identifying the cause. In this report, we present the 5-year follow up of a family with HGF and features of 3 previously described syndromes: Jones syndrome, Zimmerman-Laband syndrome, and HGF-hypertrichosis syndrome. The 45-year-old father had HGF, hypertrichosis, hearing loss, and short stubby fingers and toes with hypoplasia of the terminal phalanges and hypoplasia of the nails on the thumbs. The features of 13-year-old son were almost identical to those of his father except for hypertrichosis, but in addition he was mentally retarded. Although the 10-day-old son had HGF and defective fingers, the mother and 7-year-old daughter were unaffected. Owing to the overlap of these syndromes, we argue that the identification of the genetic pathways and mechanisms will be the most important factor in classifying these disorders, with the phenotype playing a minor role.

Rev Stomatol Chir Maxillofac. 2006 Dec; 107(6): 477-80
Kissi L, Benyahya I, Rifki A

Gingival fibromatosis is an inherited disease of the gingival tissue causing proliferative fibrous lesions occurring alone or as one feature of a more widespread syndrome.A 26-year-old girl consulted the oral surgery department for a functional problem due to the presence of two tumor masses located in the palate. The histological diagnosis was gingival fibromatosis. The presence of skeletal disorders in this patient with gingival fibromatosis suggested the diagnosis of Zimmermann Laband syndrome.Gingival fibromatosis is a rare condition characterized by a gingival hypertrophy. It is transmitted by autosomal dominant or recessive inheritance. The oral examination and histology provides the diagnosis. The treatment consistes of surgical removal of the hyperplasic fibrous tissue. Prognosis is dominated by the risk of recurrence which is frequent. Generally, gingival fibromatosis is isolated. In rare cases, it can be associated with symptoms sugges-ting a syndromic diagnosis such as Zimmermann Laband syndrome. In addition to gingival hypertrophy, skeletal anomalies can involve the fingers, the toenails, the thorax or the vertebrae. Splenomegaly and joint hyperextensibility can also be found.

Ultrastruct Pathol. 2006 Nov-Dec; 30(6): 423-6
Hoogendijk CF, Marx J, Honey EM, Pretorius E, Christianson AL

Zimmermann-Laband syndrome (ZLS) is a very rare autosomal dominant inherited condition characterized by 3 major clinical findings of which gingival hyperplasia are always present. The great heterogenicity of the syndrome is illustrated by the numerous variable clinical findings described in the literature. The purpose of the study was to examine a patient diagnosed with ZLS and to describe possible new characteristics of this rare syndrome, including the ultrastructural morphology using a transmission electron microscope (TEM) of the gingival and dermal fibroblasts. The ultrastrucutral morphology as has not previously been described in the literature. Tissue was collected from the alveolar ridge and skin of the forearm for TEM. TEM studies indicated the presence of prominent fibroblasts situated among numerous regular dense connective tissue bundles. Genetic analysis showed a new chromosomal insertion, ins(12;8)(p11.2;q11.2q24.3), suggesting that the gene responsible for the syndrome lies on chromosome 8.

Am J Med Genet A. 2007 Jan 15; 143(2): 107-11
Kim HG, Higgins AW, Herrick SR, Kishikawa S, Nicholson L, Kutsche K, Ligon AH, Harris DJ, MacDonald ME, Bruns GA, Morton CC, Quade BJ, Gusella JF

A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.

Pediatr Dev Pathol. 2005 Nov-Dec; 8(6): 654-7
Atabek ME, Pirgon O, Sert A, Toy H

Zimmermann-Laband syndrome is an inherited disorder that is characterized by abnormalities of the head, face, hands, and feet. Most children with this disorder have generalized hypertrichosis, large gingivae, and hypoplasia of the fingernails and toenails. We report a male infant who exhibited typical features of Zimmermann-Laband syndrome with an unusual histopathologic finding. Excised tissue from the infant's gingivae showed papillary projections that were composed of hyperplastic stratified squamous epithelium with different amounts of keratinization.