Case Report
Clinicul Genetics 1991: 40: 461-464
Cohen syndrome: fertility in a female patient J. P. FRYNS', F. LEMXIENS' AND H.VAN DEN BERCHE' Centre for Human Genetics, University of Leuven and 'Paediatrician, A. Z. St. Jan, Genk, Belgium In this report we describe fertility in an adult female with Cohen syndrome. She gave birth to a son, now 1.5 years old, with discrete facial stigmata and slight psychomotor retardation. Received 8 February, acceptedfor publication 22 April 1991 Key words: Cohen syndrome; mental retardation; multiple congenital anomalies/mental retardation syndrome
Since the original publication by Cohen et al. (1973), the Cohen syndrome has been further delineated as a new distinct MCA/ MR syndrome with marked intrafamilial variability (Young & Moore 1987). According to Escobar (1990), at least five of the following major diagnostic criteria should be present in an individual patient: obesity, short stature, mental retardation, hypotonia, maxillary hypoplasia, short philtrum, micrognathia, narrow hands and feet, narrow and high-arched palate. Case Report
J.L., a 1.5-year-old boy, was referred to the Genetic Clinic together with his parents for further diagnosis. He was the first and only child of this family and was born after an apparently normal pregnancy. Delivery, at 37 weeks, was without complications and birth weight was 2750 g. Medical history was further negative in the first 1.5 years of his life, but after the age of 12 to 15 months a slight psychomotor retardation became evident with marked delay in speech devel-
opment. Now, at the age of 1.5 years, gross and fine motor development was within normal limits but verbal functioning was at the level of 11 to 12 months. Clinical examination revealed a brachycephalic boy (Fig. 1) with flat occiput, slight facial oedema, bilateral epicanthus, short upper lip and a relatively short neck. Height was 79 cm, weight 10.6 kg and head circumference 46.7 cm (all values between percentiles I0 and 25 for age). Further clinical examination was normal with normal trunk and normal morphology of hands and feet, except for discrete overriding of the second and third toes. His 32-year-old father has a normal phenotype (Fig. l), is mentally normal and has a negative family history. The mother, C.J.,is now 26 years old. She is moderately mentally retarded (IQ 46 - WISC scale) and attended different schools and institutions for the moderately mentally retarded up to the age of 23 years. Her height is 163.5 cm, span 168 cm, weight 69.5 cm and head circumference 50 cm.In addition to the striking microcephaly, she
'
462
F R Y N S ET A L
flg. 1. The father and the child.
presents a rather long face with high nasal bridge, relative maxillary hypoplasia, short phi1trum, prominent upper central incisors (Fig. 2a and b), and narrow and high-arched palate. She has truncal obesity with contrasting narrow shoulders, hyperkyphosis and long, small hands (hand length: 17.5 cm and middle finger length 10.5 cm)and feet with acrocyanosis. Except for a discrete strabismus internus alternans. ophthalmological examination was normal. She is the fourth child in a family with five children: four girls and one boy. Her parents and three sisters are normal. Her only, 26-yearold, brother has borderline intelligence (IQ=72, WISC).At the present time he has no contact with his family and we have so far been unable to obtain more precise medical data. Chromosomal analysis was performed in
both parents and the child and revealed normal karyotypes with G-and R-banding. Discussion
The adult female of this report is moderately mentally retarded and microcephalic. In addition, she presents clinical signs and symptoms compatible with the clinical diagnosis of Cohen syndrome, i.e. short philtrum, prominent upper central incisors, truncal obesity, narrow hands and feet and narrow high-arched palate. Autosomal recessive inheritance has been documented after the description of affected sibs of normal parents (for review, see Young & Moore 1987). Recently we reported on a de now apparently balanced reciprocal 5q;7p translocation in a 15-yearold girl with apparent Cohen syndrome, in-
463
COHEN SYNDROME
becoming blind (Escobar 1990). As far as we know, fertility in a patient with Cohen syndrome has not been reported up to now. Delayed puberty has been noted in several studies, and Carey & Hall (1978) documented a patient with isolated gonadotropin deficiency. The 1.5-year-old son of this female with Cohen syndrome presents a discrete facial dysmorphism, but no further stigmata compatible with the diagnosis of Cohen syndrome. He shows a mild general delay in psychomotor development and a more severe delay in speech development, which may be related to the poor psychosocial stimulation of this child. However, it is interesting to note that a higher incidence of lower intelligence was reported in heterozygotes of autosomal recessive disorders, e.g. phenylketonuria (Vogel 1984) and Cohen syndrome (Fryns et al. 1986), as apparent examples of partial heterozygote manifestation.
References
Fig. 2. The general craniofacial appearance (a) with the long upper central incisors (b)in the adult female with Cohen syndrome.
dicating that the gene for Cohen syndrome is possibly at 5q33.1 or 7p15.1 (Fryns et al. 1990). Genetic heterogeneity can, however, not be fully excluded with the available data. Information on the long-term prognosis of adult patients with Cohen syndrome is scanty. Those patients with optic atrophy and chorioretinal dystrophy are at risk of
Carey, J. C. & B. D. Hall (1978). Confirmation of the Cohen syndrome. J. Pediatr 93, 239-244. Cohen, M. M., B. D. Hall, D. W. Smith, C. B. Graham & K. J. Lampert (1973). A new syndrome with hypotonia, obesity, mental deficiency and facial, oral, ocular and limb anomalies. J. Pediatr. 83, 280-284. Escobar, V. (1990). Cohen syndrome. In: Birth Defects Encyclopedia. M. L . Buyse ed., Center for Birth Defects Information Services, Inc., Dover, in association with Blackwell Scientific Publications, pp. 424-425. Fryns, J. I?, A. M. Dereymaeker, M. Hoefnagels, G. Heremans, J. Marien & H. Van den Berghe (1986). A genctic-diagnostic survey in an institutionalized population of 173 severely mentally retarded patients. Clin. Genet. 30, 315-323. Fryns, J. P., A. Kleczkowska, E. Smeets, P. Thiry, J. Geutjens & H. Van den Berghe (1990). Cohen syndrome and de novo reciprocal translocation
464
FRYNS ET A L .
t(5;7) (q33.l;p15.1). Am. J. Med. Genet. 37, 546-547. Young, I. D. & J. R. Moore (1987). Intrafarnilial
variation in Cohen syndrome. J. Med. Genet. 24, 488492.
Vogel, F. (1984). Clinical consequences of heterozygosity for autosomal recessive diseases. Ch. diner. 25, 381-415.
Address: J. I! Fryns Cenrre,-or Human Genetics 49
8-3000Leuven Belgium
Clinicul Genetics 1991: 40: 461-464
Cohen syndrome: fertility in a female patient J. P. FRYNS', F. LEMXIENS' AND H.VAN DEN BERCHE' Centre for Human Genetics, University of Leuven and 'Paediatrician, A. Z. St. Jan, Genk, Belgium In this report we describe fertility in an adult female with Cohen syndrome. She gave birth to a son, now 1.5 years old, with discrete facial stigmata and slight psychomotor retardation. Received 8 February, acceptedfor publication 22 April 1991 Key words: Cohen syndrome; mental retardation; multiple congenital anomalies/mental retardation syndrome
Since the original publication by Cohen et al. (1973), the Cohen syndrome has been further delineated as a new distinct MCA/ MR syndrome with marked intrafamilial variability (Young & Moore 1987). According to Escobar (1990), at least five of the following major diagnostic criteria should be present in an individual patient: obesity, short stature, mental retardation, hypotonia, maxillary hypoplasia, short philtrum, micrognathia, narrow hands and feet, narrow and high-arched palate. Case Report
J.L., a 1.5-year-old boy, was referred to the Genetic Clinic together with his parents for further diagnosis. He was the first and only child of this family and was born after an apparently normal pregnancy. Delivery, at 37 weeks, was without complications and birth weight was 2750 g. Medical history was further negative in the first 1.5 years of his life, but after the age of 12 to 15 months a slight psychomotor retardation became evident with marked delay in speech devel-
opment. Now, at the age of 1.5 years, gross and fine motor development was within normal limits but verbal functioning was at the level of 11 to 12 months. Clinical examination revealed a brachycephalic boy (Fig. 1) with flat occiput, slight facial oedema, bilateral epicanthus, short upper lip and a relatively short neck. Height was 79 cm, weight 10.6 kg and head circumference 46.7 cm (all values between percentiles I0 and 25 for age). Further clinical examination was normal with normal trunk and normal morphology of hands and feet, except for discrete overriding of the second and third toes. His 32-year-old father has a normal phenotype (Fig. l), is mentally normal and has a negative family history. The mother, C.J.,is now 26 years old. She is moderately mentally retarded (IQ 46 - WISC scale) and attended different schools and institutions for the moderately mentally retarded up to the age of 23 years. Her height is 163.5 cm, span 168 cm, weight 69.5 cm and head circumference 50 cm.In addition to the striking microcephaly, she
'
462
F R Y N S ET A L
flg. 1. The father and the child.
presents a rather long face with high nasal bridge, relative maxillary hypoplasia, short phi1trum, prominent upper central incisors (Fig. 2a and b), and narrow and high-arched palate. She has truncal obesity with contrasting narrow shoulders, hyperkyphosis and long, small hands (hand length: 17.5 cm and middle finger length 10.5 cm)and feet with acrocyanosis. Except for a discrete strabismus internus alternans. ophthalmological examination was normal. She is the fourth child in a family with five children: four girls and one boy. Her parents and three sisters are normal. Her only, 26-yearold, brother has borderline intelligence (IQ=72, WISC).At the present time he has no contact with his family and we have so far been unable to obtain more precise medical data. Chromosomal analysis was performed in
both parents and the child and revealed normal karyotypes with G-and R-banding. Discussion
The adult female of this report is moderately mentally retarded and microcephalic. In addition, she presents clinical signs and symptoms compatible with the clinical diagnosis of Cohen syndrome, i.e. short philtrum, prominent upper central incisors, truncal obesity, narrow hands and feet and narrow high-arched palate. Autosomal recessive inheritance has been documented after the description of affected sibs of normal parents (for review, see Young & Moore 1987). Recently we reported on a de now apparently balanced reciprocal 5q;7p translocation in a 15-yearold girl with apparent Cohen syndrome, in-
463
COHEN SYNDROME
becoming blind (Escobar 1990). As far as we know, fertility in a patient with Cohen syndrome has not been reported up to now. Delayed puberty has been noted in several studies, and Carey & Hall (1978) documented a patient with isolated gonadotropin deficiency. The 1.5-year-old son of this female with Cohen syndrome presents a discrete facial dysmorphism, but no further stigmata compatible with the diagnosis of Cohen syndrome. He shows a mild general delay in psychomotor development and a more severe delay in speech development, which may be related to the poor psychosocial stimulation of this child. However, it is interesting to note that a higher incidence of lower intelligence was reported in heterozygotes of autosomal recessive disorders, e.g. phenylketonuria (Vogel 1984) and Cohen syndrome (Fryns et al. 1986), as apparent examples of partial heterozygote manifestation.
References
Fig. 2. The general craniofacial appearance (a) with the long upper central incisors (b)in the adult female with Cohen syndrome.
dicating that the gene for Cohen syndrome is possibly at 5q33.1 or 7p15.1 (Fryns et al. 1990). Genetic heterogeneity can, however, not be fully excluded with the available data. Information on the long-term prognosis of adult patients with Cohen syndrome is scanty. Those patients with optic atrophy and chorioretinal dystrophy are at risk of
Carey, J. C. & B. D. Hall (1978). Confirmation of the Cohen syndrome. J. Pediatr 93, 239-244. Cohen, M. M., B. D. Hall, D. W. Smith, C. B. Graham & K. J. Lampert (1973). A new syndrome with hypotonia, obesity, mental deficiency and facial, oral, ocular and limb anomalies. J. Pediatr. 83, 280-284. Escobar, V. (1990). Cohen syndrome. In: Birth Defects Encyclopedia. M. L . Buyse ed., Center for Birth Defects Information Services, Inc., Dover, in association with Blackwell Scientific Publications, pp. 424-425. Fryns, J. I?, A. M. Dereymaeker, M. Hoefnagels, G. Heremans, J. Marien & H. Van den Berghe (1986). A genctic-diagnostic survey in an institutionalized population of 173 severely mentally retarded patients. Clin. Genet. 30, 315-323. Fryns, J. P., A. Kleczkowska, E. Smeets, P. Thiry, J. Geutjens & H. Van den Berghe (1990). Cohen syndrome and de novo reciprocal translocation
464
FRYNS ET A L .
t(5;7) (q33.l;p15.1). Am. J. Med. Genet. 37, 546-547. Young, I. D. & J. R. Moore (1987). Intrafarnilial
variation in Cohen syndrome. J. Med. Genet. 24, 488492.
Vogel, F. (1984). Clinical consequences of heterozygosity for autosomal recessive diseases. Ch. diner. 25, 381-415.
Address: J. I! Fryns Cenrre,-or Human Genetics 49
8-3000Leuven Belgium
