Case reports Inheritance was dominant and therefore unlike the present family. Moynahan' reported male sibs with mental subnormality, epilepsy (onset at 2 to 3 years), and alopecia which involved the scalp only. The hair later regrew. The mode of inheritance in this family is difficult to ascertain as the boy's father only grew hair at the age of 2 years and the boy's mother's sister was bald until the age of 4 years. The regrowth of the hair, the restriction of the baldness to the scalp, and the epilepsy differentiate Moynahan syndrome from the one described here. A similar condition in two sibs whose parents were con- sanguineous was reported by Perniola et al.3 Deafness occurred in both. There are at least three other syndromes in which hair loss is associated with mental retardation. Menkes disease can be excluded as the hair is kinky and not totally absent. Prognosis for life is poor and seizures are frequent. Inheritance is X linked recessive. In Monilethrix the hair is normal at birth but is then lost within the first few months. Red pustular lesions on the scalp may be present. Alopecia is seldom total and through the pustules brittle hairs which break easily emerge. The nails and teeth are abnormal and mental retardation is only occasionally a feature. In the Hair-Brain syndrome (Amish brittle hair syndrome) those affected had short stature and relatively mild mental retardation. All the affected had hair but it was brittle and broke easily. Total alopecia was not a feature and inheritance was recessive. In the condition described in this paper, the alopecia was total and involved all areas of normal hair growth. It probably represents a distinct entity. M BARAITSER, C 0 CARTER, AND E M BRETT* Clinical Genetics Unit and *Department of Neurology, The Hospital for Sick Children, Great Ormond Street, London WCIN 3JH. References Moynahan EJ. Familial congenital alopecia, mental retardation with unusual electroencephalograms. Proc R Soc Med 1962;55:411-2. 2 Shokeir MHK. Universal permanent alopecia, psycho- motor epilepsy, pyorrhoea and mental subnormality. Clin Genet 1977;11:13-17. 3 Perniola T, Krajewska G, Carnevale F, Lospalluti M. Congenital alopecia, psychomotor retardation, convul- sions in two sibs of a consanguineous marriage. J Inher Met Dis 1980;3:49-53. Requests for reprints to Dr M Baraitser, Clinical Genetics Unit, The Hospital for Sick Children, Great Ormond Street, London WCIN 3JH. 65 A female infant with features of Mohr and Majewski syndromes: variable expression, a genetic compound, or a distinct entity? SUMMARY A female child, the offspring of a consanguineous mating, had a cleft palate, tongue tumours, hypoplastic tibiae, and poly- syndactyly. The relationship to the Mohr and Majewski syndromes is discussed. Variable expression is a common problem en- countered by those who seek to define syndromes. The best method to determine the extent of the phenotypic expression of a gene defect is to study the variability within sibships, but in rare disorders this is not always possible. It is then necessary to depend on somewhat arbitrary definitions. The Mohr and Majewski syndromes each behave as a probable autosomal recessive disorder1 2 with a relatively distinct phenotype. Temtamy and Mc- Kusick3 reported two subjects whose clinical features fulfilled the definition of both syndromes. We report a female infant, the second child of consanguineous parents, in whom combined features of both syndromes were seen. Case report The patient was born on 9.9.81 at 33 weeks' gestation weighing 1520 g. She was the second child of first cousin Pakistani Moslem parents. The mother and father were 19 and 21 years old, respectively. A sib was normal and there was no relevant family history. The child (fig 1) was noted to have low set ears, micrognathia, and shallow orbits causing mild proptosis. There was a high arched palate with a posterior cleft and fleshy tumours were present on the underside of the tongue. Bilateral postaxial polysyndactyly was noted in the hands with poly- syndactyly, severe talipes equinovarus, and distal shortening of both lower limbs. At 6 months her weight of 4- 2 kg was well below the 3rd centile. She fed poorly and had frequent chest infections. Her development was slightly delayed. Radiological examination revealed severe bilateral tibial dysplasia (fig 2), whereas the chest x-ray did not show significant rib shortening. There was a normal 46,XX karyotype. Received for publication 23 July 1982. o n A p ril 5 , 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://jm g .b m j.co m / J M e d G e n e t: first p u b lish e d a s 1 0 .1 1 3 6 /jm g .2 0 .1 .6 5 o n 1 F e b ru a ry 1 9 8 3 . D o w n lo a d e d fro m http://jmg.bmj.com/ Case reports FIG 1 (a) Facial appearance ofproband. Note flat nasal bridge andprominent eyes. (b) Sublingual fleshy tumours. (c) Postaxial polydactyly of hands. (d) Pre- and postaxial polydactyly and severe talipes affecting both feet. FIG 2 X-ray appearance of limbs. Note hypoplasia of tibia. ,:::.s. . Discussion The similarities between the orofacial digital syn- drome type (Mohr syndrome) and the short rib polydactyly syndrome type (Majewski syndrome) are shown in the table. It is apparent that mid-facial flattening, hyper- telorism, tongue tumours, and multiple frenulae may occur in both syndromes. The Majewski syndrome is distinguishable by the presence of short ribs, probably a major factor in the invariable neonatal death, and hypoplasia of the tibiae. In Mohr syndrome, survival is the rule and the tibiae are not hypoplastic. Possible exceptions have occurred. Spranger et a14 gave a brief report of a patient with features of Majewski syndrome whose sib might have been similarly affected and survived for 40 minutes. Rimoin and Edgerton5 reported a family in which a brother and sister had the typical features of Mohr syndrome, whereas a third sib who 66 ;Ift I.w 0 o n A p ril 5 , 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://jm g .b m j.co m / J M e d G e n e t: first p u b lish e d a s 1 0 .1 1 3 6 /jm g .2 0 .1 .6 5 o n 1 F e b ru a ry 1 9 8 3 . D o w n lo a d e d fro m http://jmg.bmj.com/ rABLE Comparison of clinical features in the present patient with those of Alohr and Majewski syndromes. Majewski syndrome Mohr syndrome Present patient Oral manifestations Median cleft, or pseudo-cleft of Pseudo-cleft tongue tumours, Tongue tumours, exaggerated upper lip exaggerated multiple frenulae multiple frenulae Deafness ? + ? Nose Broad and flat Broad and flat Broad and flat Eyes Hypertelorism Hypertelorism Hypertelorism Hand Postaxial polydactyly Pre- and postaxial polydactyly Postaxial polydactyly Foot Postaxial polydactyly Pre-axial polydactyly Postaxial polydactyly Tibia Hypoplastic Normal Hypoplastic Thorax Narrow Normal Normal Perinatal death + Inheritance AR AR ?AR (parental consanguinity) was stillborn had the digital malformations and a cleft lip and palate, identical to those seen in the surviving sibs. X-rays of the lower limbs of the surviving sibs showed the proximal metaphysis of the tibiae and fibulae to be wide and misshapen. The proximal epiphysis of the tibiae and the distal epiphysis of the fibulae were flattened. The x-rays of the sib who died were not available. Temtamy and McKusick3 reported two patients who combined the features of the two syndromes. In the first, there was a median pseudo-cleft of the upper lip, multiple frenulae, a normal tongue with a single yellow nodule on the lateral border, poly- dactyly, and syndactyly; the infant died at 71 weeks following an aspiration. This was probably related to a hypoplastic epiglottis thought to be character- istic of the Majewski syndrome. X-rays of the tibiae were not shown. The second case had a small thorax, but survived despite respiratory problems in infancy. The limbs were short, particularly the tibiae which had rounded upper metaphyses. The facial features were compatible with either syndrome. The present case represents, perhaps, the best illustration to date of a patient falling midway between the two conditions. The normal thorax and prolonged survival are against the diagnosis of Majewski syndrome, while the severe hypoplasia of the tibiae is against the diagnosis of Mohr syndrome. The child may be regarded as either a mild example of Majewski syndrome or an unusually severe example of Mohr syndrome. The general tendency of these syndromes to 'breed true' is some- what against an explanation that suggests the two syndromes are not distinct. A third possibility is that the child represents a compound heterozygote for separate recessive alleles. The consanguinity in the parents is more in favour of homozygosity for a single abnormal allele within the family. A fourth possibility is that this child is homozygous for a distinct recessive gene defect, possibly disturb- ing a similar developmental pathway to that involved in the other syndromes. The consanguinity of the parents provides support for this possibility, though in view of the high level of inbreeding in the population from which this family originates, cousin marriage in the parents is of less significance. In each of these four explanations, it is implied that children with the features described in the present report have a recessive condition and that the parents face a I in 4 risk of recurrence. M BARAITSER*, J BURNt, AND J FIXSEN* *The Hospitalfor Sick Children, Great Ormond Street, Londont WCIN 3JH; and tMRC Clinical Genetics Unit, Institute of Child Health, 30 Guilford Street, Lonidon WCIN JEH. References Gorlin RJ, Pindborg JJ, Cohen MM. Syndrotnes of the head and neck. 2nd ed. New York: McGraw-Hill, 1976: 568-70. 2 Black IL, Fitzsimmons J, Fitzsimmons E, Thomas AJ. Parental consanguinity and the Majewski syndrome. J Med Genet 1982;19:141-57. 3 Temtamy S, McKusick V. The genetics of hand malforma- tions. Birth Defects 1978;XIV:No 3. 4 Spranger J, Grimm B, Weller M, et al. Short rib-poly- dactyly (SRP) syndromes, types Majewski and Saldino- Noonan. Z Kinderheilkd 1974;116:73-94. 5 Rimoin DL, Edgerton MT. Genetic and clinical hetero- geneity in the oral-facial-digital syndromes. J Pediatr 1967;71 :94. Requests for reprints to Dr M Baraitser, Clinical Genetics Unit, The Hospital for Sick Children, Great Ormond Street, London WCIN 3JH. Addendum Since the submission of this report for publication, a second affected child has been born to these parents. The infant has the same clinical and radio- logical features, details of which will be provided in a future report. This development adds weight to the view that this syndrome results from a distinct autosomal recessive gene defect. Case reports 67 o n A p ril 5 , 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://jm g .b m j.co m / J M e d G e n e t: first p u b lish e d a s 1 0 .1 1 3 6 /jm g .2 0 .1 .6 5 o n 1 F e b ru a ry 1 9 8 3 . D o w n lo a d e d fro m http://jmg.bmj.com/