Solitary Median Maxillary Central Incisor

A number sign (#) is used with this entry because of evidence that solitary median maxillary central incisor (SMMCI) and SMMCI syndrome are caused by heterozygous mutation in the Sonic hedgehog gene (SHH; 600725) on chromosome 7q36.

Clinical Features

Rappaport et al. (1976, 1977) reported 7 unrelated patients with single (unpaired) deciduous and permanent maxillary central incisors and short stature. Five of them had isolated growth hormone deficiency. The other 2 had normal growth hormone responses but were short of stature. No similar or possibly related abnormalities were present in the 7 families. Rappaport et al. (1976) used the term monosuperoincisivodontic dwarfism to describe the association of short stature and solitary incisor.

Berry et al. (1984) described a single upper central incisor associated with holoprosencephaly in a semidominant pedigree.

Winter et al. (1982) found a single central upper incisor in association with precocious puberty and hypothalamic hamartoma.

Hattori et al. (1987) described holoprosencephaly (see 147250) in a child born to a mother with single central maxillary incisor. The infant had a median cleft lip, flat nose with a single nostril, hypotelorism, and normal chromosomes. CT scan of the brain showed semilobar holoprosencephaly. The mother had mild hypotelorism but no anosmia, and her brain CT was normal. She was of normal intelligence and stature. Other relatives did not have single central maxillary incisors, hypotelorism, or oral clefts.

Liberfarb et al. (1987) described a patient with ocular coloboma associated with a single central incisor and growth failure. The mother had hyposmia, leading the authors to suggest that the case represented an autosomal dominant form of holoprosencephaly.

Winter et al. (1988) and Buntinx and Baraitser (1989) described a single central maxillary incisor in patients with a form of ectodermal dysplasia.

Artman and Boyden (1990) described a patient with microphthalmia and isolated growth hormone deficiency in association with single central incisor.

Hall et al. (1997) described a series of 21 consecutive cases of solitary median maxillary central incisor syndrome seen in the Royal Children's Hospital in Melbourne, Australia, from 1966 to 1997. The spectrum of anomalies and associated features present in these cases, including short stature, choanal atresia, midnasal stenosis, and holoprosencephaly, was described. They pointed out that SMMCI syndrome, previously considered a simple midline defect of the dental lamina, is a possible predictor of holoprosencephalies of varying degree in the proband, members of the proband's family, and in the family's descendants. Hall et al. (1997) commented that it was not surprising that the association of a solitary incisor with the midline nasal cavity defects of choanal atresia, midnasal stenosis, and nasal pyriform aperture stenosis was not noted earlier, because these potentially life-threatening neonatal causes of airway obstruction are managed surgically in the immediate neonatal period, months before the eruption of the maxillary incisor tooth during the second half of the first year of life. Arlis and Ward (1992) recognized the association of solitary central incisor with nasal obstruction. Hall et al. (1997) stated that the presence of a solitary symmetrical maxillary central incisor of normal crown dimensions situated precisely in the midline in both primary and permanent dentitions was apparently first reported by Scott (1958).

Nanni et al. (2001) reviewed the extensive number of anomalies in addition to holoprosencephaly with which solitary median maxillary central incisor had been reported.


Fused central incisors is a feature of the 18p- phenotype. Dolan et al. (1981) and Aughton et al. (1991) reported cases of del(18p) syndrome and single maxillary central incisor.

Masuno et al. (1990) described 2 unrelated cases of single maxillary central incisor with 7q terminal deletion. They had mental retardation, microcephaly, hypotelorism, short stature, and normal levels of plasma growth hormone. One patient had bilateral caudal ectopic kidneys, double renal pelvises, and dilated ureters. The other had bilateral hydroureteronephrosis. Masuno et al. (1990) suggested that 7q terminal deletion is one of the causes of SMMCI.

Molecular Genetics

Nanni et al. (2001) performed a molecular study of 13 patients with solitary median maxillary central incisor who did not have holoprosencephaly. They studied 2 genes, SHH (600725) and SIX3 (603714), in which mutations had been reported in patients showing SMMCI as part of the holoprosencephaly spectrum. They found a new missense mutation in SHH (I111F; 600725.0014) which may be specific for the SMMCI phenotype since it had not been found in patients with holoprosencephaly or in normal controls.

Marini et al. (2003) studied a family, previously described by Camera et al. (1992), in which the mother presented with a single central maxillary incisor and mild hypotelorism and her daughter and 2 fetuses were diagnosed with HPE. Sequencing of DNA in this family identified a nonsense mutation in the SHH gene (600725.0019).