Mohr Syndrome

Clinical Features

Norwegian geneticist Otto L. Mohr (1941), uncle of Professor Jan Mohr of Copenhagen, described a family in which 4 males of a sibship of 5 boys and 2 girls showed a syndrome which was detailed in the case of 1 affected male whom he personally observed. The features were poly-, syn-, and brachydactyly, lobate tongue with papilliform protuberances, angular form of the alveolar process of the mandible, supernumerary sutures in the skull, and an episodic neuromuscular disturbance. Three of the 4 affected males had died prior to the time of report. One of these had cleft palate.

Rimoin and Edgerton (1967) described 3 affected sibs, 2 male and 1 female.

In addition to the different mode of inheritance, Mohr syndrome shows none of the skin and hair changes of X-linked orofaciodigital syndrome I (OFD1; 311200), but does show conductive hearing loss and bilateral hallucal polysyndactyly not present in OFD I. Tachypnea is commonly noted in this syndrome (Gorlin, 1982). Anneren et al. (1984) made a useful differentiation between the features of OFD I and OFD II.

Gustavson et al. (1971) reported 2 affected sisters. Haumont and Pelc (1983) described 2 sisters who, in addition to the usual features of the Mohr syndrome, had the Dandy-Walker syndrome. They suggested that the association of brain abnormalities may reflect the existence of a second distinct form of the Mohr syndrome. Egger and Baraitser (1984) suggested that the sibs reported by Gustavson et al. (1971) and by Haumont and Pelc (1983) had Joubert syndrome (213300), not Mohr syndrome.

Goldstein and Medina (1974) described talon cusps in Mohr syndrome.

Silengo et al. (1987) presented 2 patients who they suggested lent support to the idea that Mohr syndrome and Majewski syndrome (263520) are mild and severe expressions, respectively, of the same autosomal recessive disorder. The 2 patients had features typical of OFD II or Mohr syndrome but also had laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet typical of Majewski syndrome. In the latter condition, the oral/facial findings are almost identical to those of the Mohr syndrome. Gillerot and Koulischer (1988) also observed a newborn with overlapping features of the Majewski and Mohr syndromes. Reardon et al. (1989) described a boy who had features of the Mohr syndrome as well as a large arachnoid cyst compressing the cerebellum and brainstem. Typically in the Mohr syndrome, the hands show postaxial polydactyly and the feet show preaxial polydactyly. Anneren et al. (1990) described 2 patients with Mohr syndrome associated with cerebellar atrophy and found reports of 3 cases of cerebellar abnormalities in this disorder.

Prpic et al. (1995) reported Mohr syndrome in 2 male sibs who had different phenotypic features. One had typical oral, facial, and digital anomalies plus hypoplastic genitalia and short limbs. He was markedly hypotonic and had convulsions and apneic episodes and died shortly after birth. His younger brother had OFD features with conductive hearing loss and normal psychomental development. He did not have syndactylous reduction of the great toes, although the toes were disproportionately large.

Balci et al. (1999) reported 2 sisters with Mohr syndrome from a consanguineous family. One was a 3-day-old patient, and the other a 22-week-old fetus diagnosed prenatally by the ultrasound finding of gross skeletal abnormalities of the hands and feet. At autopsy, besides the typical physical abnormalities of Mohr syndrome, the fetus showed natal teeth and absence of olfactory nerve, 2 features not previously reported in this syndrome. The authors stressed that the prenatal diagnosis of Mohr syndrome is possible with early ultrasonographic examination.

Hsieh and Hou (1999) reported the case of a boy with pseudocleft of the upper lip, cleft palate, bifid uvula, lobulated tongue, hypoplasia of the epiglottis, both preaxial and central polydactyly of the hands (Y-shaped fourth metacarpals), bilateral preaxial polydactyly of the feet, postaxial polydactyly of the cleft foot, hearing impairment, and congenital heart disease with endocardial cushion defect. These clinical manifestations resembled orofaciodigital syndrome type II or type VI (OFD6; 277170). They stated that to the best of their knowledge this was the first reported case of OFD type II with Y-shaped fourth metacarpals. They raised the question of whether Mohr syndrome with Y-shaped fourth metacarpals, atrioventricular canal defect, and hypoplasia of the epiglottis may represent an additional type of orofaciodigital syndrome.

Panigrahi et al. (2013) reported 2 patients with overlapping features of OFD type II and type VI. Y-shaped metacarpal, central polydactyly, and renal disease were characteristic of type VI, whereas face and hand abnormalities and cardiac defect were suggestive of type II. Panigrahi et al. (2013) suggested that types II and VI are part of the same phenotypic spectrum with serious intracranial abnormalities at the more severe end of the spectrum.

Inheritance

In the family described by Mohr (1941), no similarly affected persons in previous generations were known. The parents were not related. Although Mohr suggested that the syndrome was due to a recessive, sublethal, X-linked gene, the evidence for this was feeble. Claussen (1946) provided a follow-up of the kindred with description of an affected male cousin. Furthermore, the parents of the new case were related. He suggested autosomal recessive inheritance, which seems to be supported by the observation by Gorlin (1967) of the same syndrome in 2 sisters.

Nomenclature

Rimoin and Edgerton (1967) suggested that Mohr syndrome might be called the oral-facial-digital syndrome II.