Expanding the phenotype of gingival fibromatosis–mental retardation–hypertrichosis (Zimmermann–Laband) syndrome

Abstract

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.

Syndromes with supernumerary teeth

“…Castori et al [] reviewed 52 patients. Of these, three had ST [Chadwick et al, ; Holzhausen et al, ; Chacon‐Camacho et al, ], ranging from one to five in number. We conclude that this is probably a chance finding in a condition where gingival‐related issues make dental radiographs, and the consequent ascertainment of coincidental ST more likely.…”

Intellectual Disability: When the Hypertrichosis Is a Clue

“…Literature review showed that the main features of the syndrome are gingival hypertrophy associated with nails or terminal phalanges hypo/aplasia (100% of patients). [43][44][45][46][47][48][49][50] In more than 50% of the patients, a typical facial appearance is detectable, characterized by thick ears, large and bulbous nose, and thick lips with or without macrostomia. Common reported clinical features are moreover ID (more than 40%), joints hypermobility (48%), hypertrichosis of the face and/or the body (37%), hepatosplenomegaly (27%), and seizures (13%).…”

“…50 Clinical variability is wide even in the same family, and, as commonly observed, the seriousness of the somatic involvement often does not correlate with the severity of the ID. Several other rarer signs have been reported, as pigmentation disorders, 43,49 supernumerary teeth, 45,46,49 ocular anomalies, 47,49 and others. 44,48,49 This wide spectrum of clinical presentations of ZLS reported in the literature could be partly due to the absence, to date, of any confirmatory diagnostic test aimed at clearly defining the ZLS phenotype as compared with the overlapping conditions (DOOR and Cantù syndromes).…”

“…Several other rarer signs have been reported, as pigmentation disorders, 43,49 supernumerary teeth, 45,46,49 ocular anomalies, 47,49 and others. 44,48,49 This wide spectrum of clinical presentations of ZLS reported in the literature could be partly due to the absence, to date, of any confirmatory diagnostic test aimed at clearly defining the ZLS phenotype as compared with the overlapping conditions (DOOR and Cantù syndromes). However, Kortüm and colleagues 51 have just reported that heterozygous missense mutations in KCNH1 leading to gain-of-function effect account for a considerable proportion of ZLS, and that recurrent de novo missense change in ATP6V1B2 could be a second molecular cause of ZLS.…”

Congenital generalized hypertrichosis terminalis: a proposed classification and a plea to avoid the ambiguous term “Ambras syndrome”

“…From 11 affected individuals, all of the four examined males had severe hypertrichosis associated with scoliosis (plus spina bifida in one case only), whereas all affected females had only mild hypertrichosis. Another group of patients with less dense and extensive CGHT show mostly multiple congenital abnormalities of greater severity and compromised life expectancy [1,[24][25][26][27][28][29][30]. These may include autosomal dominant diseases, such as Cantú syndrome, Cornelia de Lange syndrome, Barber-Say syndrome, Schinzel-Giedion syndrome and Zimmermann-Laband syndrome (table 2), and autosomal recessive diseases with a very early onset of severe insulin resistance and acanthosis nigricans, such as Rabson-Mendenhall syndrome, Donohue syndrome and Berardinelli-Seip syndrome (table 3).…”