American Journal of Medical Genetics 36:89-93 (1990)
New Syndrome A New Syndrome of Dwarfism, Brachydactyly, Nail Dysplasia, and Mental Retardation in Sibs Hidefumi Tonoki, Tatsuya Kishino, and Norio Niikawa Department of Pediatrics, Hokkaido University School of Medicine, Sapporo (H.T., T.K.); Department of H u m a n Genetics, Nagasaki University School of Medicine, Nagasaki (N.N.),Japan
We describe a new multiple congenital anomaly/mental retardation (MCA/MR)syndrome in chromosomally normal sibs. Both had microcephaly, a “coarse” face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a “coarse” face, digital anomalies, dwarfism, and severe mental retardation.The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X-linked semidominant gene.
KEY WORDS: type B brachydactyly, autosoma1 dominant inheritance, X-linked inheritance, dermatoglyphic abnormality INTRODUCTION Q p e B brachydactyly is a rare anomaly representing short middle phalanges with short or absent terminal phalanges of fingers and toes. Type B brachydactyly usually occurs a s a n isolated anomaly, but it has also been seen in several syndromes, e.g., Sorsby syndrome, Keutel syndrome, Larsen syndrome, Berk-Tabatznik syndrome, Coffin-Siris syndrome, Rudiger syndrome, and otopalatoidigital syndrome [Temtamy and McKusick, 1978; Bergsma, 19791. Familial occurrences of brachydactyly have been recently reported in a few new malformation syndromes [Cooks et al., 1985; Pitt
kceived for publication July 3, 1989; revision received October 11, 1989. Address reprint request to Hidefumi Tonoki, M.D., Department of Pediatrics, Hokkaido University School of Medicine, N-15, W-7, Sapporo 060, Japan.
0 1990 Wiley-Liss, Inc.
and Williams, 1985; Kumar and Levick, 19861. This report deals with a previously apparently unrecognized malformation syndrome of type B brachydactyly, dwarfism, and mental retardation in sibs.
CLINICAL REPORT Patient 1 The propositus (Fig. 1,111-7)was a 13-year-oldboy. He was born to unrelated parents after 41 weeks of gestation, weight 2,650 g, length 46 cm, and head circumference (OFC) 31 cm. When he was born, the ages of the mother and the father were 24 and 27 years, respectively. The mother had no history of drug intake, febrile illness, or radiation exposure during pregnancy. She had had no convulsive disorder. Neonatally, the patient had feeding difficulties. His further growth was delayed. His height a t age 5 years was 89.5 cm ( - 4.1 SD) with the carpal bone age of 4.0 years. Psychomotor development was delayed: head control a t 4 months, sat at 9 months, walked (without support) a t 30 months; his developmental quotient (DQ) at 5 years was less than 50. When examined by us at 13 years, his weight was 21 kg ( - 2.9 SD), height 122 cm ( - 4 . 4 SD), OFC 46 cm (-5.5 SD), arm span 126 cm. The following abnormalities were observed: microcephaly, a “coarse” face, facial hirsutism with low anterior hair line, mild synophrys, strabismus externus, crowded teeth, malformed ears, narrow shoulders, mild thoracic kyphosis, ventricular septa1 defect (spontaneously closed), bilateral cryptorchidism, a “buried” penis, long limbs compared to height, and digital and nail anomalies (Fig. 2). The digital anomalies, including abnormal roentgonographic findings, are shown in Table I. Dermatoglyphyic findings were nine arch and one whorl patterns and bilateral simian creases. The atd angles were normal bilaterally. Radiographic findings, other than those in hands and feet, included thoracic kyphosis, and lumbar lordosis, but no abnormal calcifications in the brain nor increased digital markings on the skull. An intravenous pyelogram was normal. Computerized tomography (CT) of the brain was normal. His carpal bone age was 11 years. Routine laboratory investigations, including blood chemistry and metabolic screening in the urine, showed normal results. The Giemsa trypsin-G (GTG) banded chromosomes were normal.
90
Tonoki et al.
I
I1
m Fig. 1. Family pedigree. 6 ,brachydactyly;
+, nail anomaly; @, mental retardation; @, dwarfism.
Patient 2 The younger brother of the propositus (Fig. 1, 111-8) was 11years old. He was born a t 41 weeks with a weight of 3,100 g, length 49 cm, and OFC 32 cm. In spite of good feeding, his growth was retarded. At age 13/12year, his weight was 6.5 kg; and at age 3 years, weight was 8.2 kg and height 80 cm (-4.0 SD). His carpal bone age at 28/12 years was estimated at 2 years. During the first 4 years of his life, mental retardation was not remarkable. When examined by us at age 11years, his height was 118 cm ( - 3.6 SD), weight 23 kg ( - 1.8SD), OFC 50 cm ( - 2.4 SD), arm span 112.5 cm, and I& 59. The following abnormalities was noted: microcephaly,a flat and round face, crowded teeth, overfolded ears, congenital muscular torticollis (correctedby operation at age 26/12 years), mild thoracic kyphosis, hydrocele of the testis and bilateral anomalies of fingers, toes and nails (Fig. 3). The digital anomalies, including abnormal roentgenographic findings, are shown in Table I. Dermatoglyphic findings were four arch patterns but no simian crease. The atd angles were normal. Skull roentgenography and the brain computed tomography (CT) and intravenous pyelography were normal. His carpal bone age was 11years. His GTG-banded chromosomes were nor-
mal. Routine laboratory investigations gave normal findings. The mother (Fig. 1,II-5) was born to unrelated, phenotypically normal parents. When seen by us, she was 37 years old, 144 cm tall ( - 2.6 SD), and a mentally dull woman. She had no digital anomalies except for hypoplastic nails. Her dermatoglyphic finding was seven arch patterns. Her face resembled that of her sons but was not “coarse.” She had no vertebral anomalies. A younger brother of the mother (Fig. 1, 11-61, who died of pneumonia a t age 17 years, was short and had severe mental retardation; he was 140 cm tall ( - 5.3 SD) at 17 years. Finger and nail anomalies were noted by his relatives but not examined in detail by us. His photographs suggested that his face was similar to that of the propositus. The mother’s sisters (Fig. 1, 11-1,2,4,7) were all 145-152 cm tall and other brothers (Fig. 1,II-3,8) were 165-170 cm tall. They all had normal intelligence and had no abnormalities in their faces,fingers, nails, and in the vertebrae. The father (Fig. 1,11-12)was 159 cm tall with normal intelligence, and his sibs were all normal. The first cousin of the propositus (Fig. 1, 111-2) suf-
TABLE I. Digital and Nail Anomalies by Inspection and Roentgenographic Studies of the Propositus and the Brother
Brachydacty ly Clinodactyl y Camptodactyly Partial syndactyly Broad fingers or toes Nail deformity Nail hypoplasia Nail defect Absent distal phalanx Short distal phalanx Short middle phalanx Phalangeal fusion
Affected digits in the propositus Fingers Toes ~Right Left Right Left
Affected digits in the brother Fingers Toes ~ _ _ _ _ _ _ Right Left Right ~Left
I1 V 11-v 111-IV
I1 V
I1 V 11-v
V
11-IV I
11-IV I
11-IV
11-111 I
1-111 I1
I I1
I1
I1
11-v 11-v
I1
I1 I1 111-v 11-v
~~
11-v 11-111
11-v I1
11-111 I
Dwarfism-Brachydactyly-Mental Retardation
91
Fig. 2. Propositus at age 13 years: Facial appearance (A),whole body (B), hands (C), hand roentgenogram (D), and feet (El.
fered from renal failure but had no clinical findings resembling to those of the propositus.
DISCUSSION The propositus had microcephalus, a coarse face, bilateral brachydactyly, nail anomalies, excess fingertip arch patterns, dwarfism, cryptorchidism, vertebral
anomalies, and severe mental retardation; his younger brother had similar manifestations without excess fingertip arch patterns, a coarse face, and cryptorchidism. However, the facial appearance of the sibs was similar. Brachydactyly of index fingers, a n interdigital webbing, broad first toes, partial syndactyly of toes, and clinodactyly of fifth fingers are common manifestations of both
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Tonoki et al.
Fig, 3. The younger brother at age 11 years: Facial appearance (A), whole body (B), hands (C) hand roentgenogram (D), and feet (El.
sibs. Nails were affected more severely in the propositus than in the younger brother. Abnormal x-ray findings in their hands included the absence and/or shortness of the distal phalanx of fingers 11, distal phalanges of fingers 111-V, and middle phalanges of fingers 11-V, corresponding to the type B brachydactyly [Temtamy and McKusick, 19781, although the defects were not com-
pletely symmetrical. In addition, our patients had the following manifestations in common: dwarfism, microcephalus, characteristic face, vertebral anomalies, and mental retardation. To our knowledge, familial occurrence of the association of those abnormalities has not been reported previously. A number of malformation syndromes are known to
Dwarfism-Brachydactyly-MentalRetardation
represent type B brachydactyly [Temtamy and McKusick, 19781. Brachydactyly in Sorsby syndrome is similar to that in the present cases. However, macular coloboma and renal anomalies were not present in our patients. Likewise, Keutel syndrome, Larsen syndrome, and Berk-Tabatznik syndrome are also incompatible with the malformation complex seen in our patients. Coffin-Siris syndrome resembles the manifestations of our patients because of dwarfism, mental retardation, bushy eyebrows, microcephaly, retarded bone age, and onychodystrophy. However, the facial appearance and deformity in the little fingers of our patients differentiate this entity from Coffin-Siris syndrome. Rudiger syndrome is characterized by developmental failure, coarse face, short fingers, and hypoplastic nails with short middle phalanges and rudimentary distal phalanges, abnormal dermatoglyphic patterns, including bilateral simian creases and simple arches in all digits, thickened palms and soles, cleft soft palate, and ureteral stenosis [Rudiger et al., 19711. Although most of the manifestations observed in our patients are compatible with this syndrome, lack of thickening of palms and soles, cleft soft palate, and urinary tract anomalies, and difference in the face differentiate the malformation complex in our patients from this syndrome. Some other malformation syndromes representing miscellaneous types of brachydactyly must be discussed. Otopalatodigital (OPD) syndrome is a multiple congenital anomaly/mental retardation (MCA/MR) syndrome of mental retardation, small stature, cleft soft palate, small trunk, broad distal digits with short nails, limited elbow extension, characteristic face, and deafness [Bergsma, 19791. Although the manifestations of the propositus of our family seem similar, he had no hearing loss, limited extension of elbow, cleft palate, nor shortness of third to fifth metacarpals, concluding that he was not affected with OPD syndrome. F’reaxial brachydactyly, brachycamptodactyly syndrome, Leri pleonostenosis, and Robinow syndrome can readily be distinguished from the malformation complex of our patients on the basis of their respective manifestations. Recently, Kumar and Levick [1986] reported familial occurrence of type B brachydactyly and ectrodactyly. However, none of the affected patients in their report had any manifestations similar to our patients except for digital anomaly. Neither a new nail dysplasia syndrome reported by Cooks et al. [1985] nor a new brachydactyly syndrome reported by Pitt and Williams [1985] is compatible to the manifestations of our patients. Tonoki e t al. [1988] reported a new malformation syndrome with cryptomicrotia and short, stubby fingers with excess fingertip arch patterns in a mother and son. Increased arch patterns in dermatoglyphics and brachytelomesophalangy described in their report are similar to digital anomalies of patients in this report; however, a lack of mental and developmental delay is incompatible with findings in our patients. Several malformation syndromes of camptodactyly are newly published [Baraitser, 1982; Rozin et al., 1984; Khaldi et al., 19881. Camptodactyly is observed in our propositus;
93
however, many characteristic manifestations of our patients-such as brachydactyly, nail anomaly, and peculiar face-are absent in the patients in their reports. Maternal intake of anticonvulsants, including valproate during pregnancy, and TORCH syndrome may result in nail anomalies; however, the history during pregnancy and clinical examinations showed no evidence of these problems. Finally, these differential diagnoses suggest that the malformation complex in our sibs is a new clinical entity. The mother of the propositus in our family seemed to be affected because she had short stature, hypoplastic nails and mental deficiency. Although she had no brachydactyly, the existence of excess fingertip arch patterns suggests that she is mildly affected. It is most likely that the younger brother of the mother was also affected. Several genetic mechanisms are conceivable for the occurrence of the disorder in our family. Mental retardation, short stature, and brachydactyly may be attributable to the pleiotropic effect of a n autosomal dominant gene with variable expression that originates in either of the maternal grandparents. Because definitely affected individuals in this family are all males and the female who transmitted the gene to both her sons is mildly affected, a n X-linked semidominant mode of inheritance is a n alternative explanation.
ACKNOWLEDGMENTS The authors thank Dr. N. Matsuura, M.D., for referral of the family. REFERENCES Baraitser M (1982): A new camptodactyly syndrome. J Med Genet 19:40-43. Bergsma D (1979):Birth Defects Compendium. 2nded. New York: Alan R. Liss, Inc., for The National Foundation-March of Dimes. Cooks RG, Hertz M, Katznelson MBM, Goodman RM (1985):A new nail dysplasia syndrome with onychonychia and absence andior hypoplasia of distal phalanges. Clin Genet 27:85-91. Khaldi F, Bennaceur B, Hammou A, Hamza M, Gharbi HA (1988):An autosomal recessive disorder with retardation of growth, mental deficiency, ptosis, pectus excavatum and camptodactyly. Pediatr Radio1 18:432-435. Kumar D, Levick RK (1986): Autosomal dominant onychodystrophy and anonychia with type B brachydactyly and ectrodactyly. Clin Genet 30:219-225. Pitt P, Williams I(1985): A new brachydactyly syndrome with similarities to Julia Bell types B and E. J Med Genet 22:202-204. Rozin MM, Hertz M, Goodman RM (1984): A new syndrome with camptodactyly, joint contractures, facial anomalies, and skeltal defect: A case report and review of syndromes with camptodactyly. Clin Genet 26:342-355. Rudiger RA, Schmidt W, Loose DA, Passarge E (1971):Severe developmental failures, distal limb hypoplasia, thickened palmar creases, bifid uvula, and ureteral stenosis: A previously unidentified familial disorder with lethal outcome. J Pediatr 79:977-981. Temtamy S, Mckusick VA (1978):The Genetics of Hand Malformations. New York: Alan R. Liss, Inc., for The National Foundation-Marchof Dimes. BD:OAS XIV(3):187-299. Tonoki H, Ohura T, Niikawa N (1988): Cryptomicrotia and short stubby fingers with excess fingertip arch patterns in a mother and son. Am J Med Genet 29:857-862.
New Syndrome A New Syndrome of Dwarfism, Brachydactyly, Nail Dysplasia, and Mental Retardation in Sibs Hidefumi Tonoki, Tatsuya Kishino, and Norio Niikawa Department of Pediatrics, Hokkaido University School of Medicine, Sapporo (H.T., T.K.); Department of H u m a n Genetics, Nagasaki University School of Medicine, Nagasaki (N.N.),Japan
We describe a new multiple congenital anomaly/mental retardation (MCA/MR)syndrome in chromosomally normal sibs. Both had microcephaly, a “coarse” face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a “coarse” face, digital anomalies, dwarfism, and severe mental retardation.The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X-linked semidominant gene.
KEY WORDS: type B brachydactyly, autosoma1 dominant inheritance, X-linked inheritance, dermatoglyphic abnormality INTRODUCTION Q p e B brachydactyly is a rare anomaly representing short middle phalanges with short or absent terminal phalanges of fingers and toes. Type B brachydactyly usually occurs a s a n isolated anomaly, but it has also been seen in several syndromes, e.g., Sorsby syndrome, Keutel syndrome, Larsen syndrome, Berk-Tabatznik syndrome, Coffin-Siris syndrome, Rudiger syndrome, and otopalatoidigital syndrome [Temtamy and McKusick, 1978; Bergsma, 19791. Familial occurrences of brachydactyly have been recently reported in a few new malformation syndromes [Cooks et al., 1985; Pitt
kceived for publication July 3, 1989; revision received October 11, 1989. Address reprint request to Hidefumi Tonoki, M.D., Department of Pediatrics, Hokkaido University School of Medicine, N-15, W-7, Sapporo 060, Japan.
0 1990 Wiley-Liss, Inc.
and Williams, 1985; Kumar and Levick, 19861. This report deals with a previously apparently unrecognized malformation syndrome of type B brachydactyly, dwarfism, and mental retardation in sibs.
CLINICAL REPORT Patient 1 The propositus (Fig. 1,111-7)was a 13-year-oldboy. He was born to unrelated parents after 41 weeks of gestation, weight 2,650 g, length 46 cm, and head circumference (OFC) 31 cm. When he was born, the ages of the mother and the father were 24 and 27 years, respectively. The mother had no history of drug intake, febrile illness, or radiation exposure during pregnancy. She had had no convulsive disorder. Neonatally, the patient had feeding difficulties. His further growth was delayed. His height a t age 5 years was 89.5 cm ( - 4.1 SD) with the carpal bone age of 4.0 years. Psychomotor development was delayed: head control a t 4 months, sat at 9 months, walked (without support) a t 30 months; his developmental quotient (DQ) at 5 years was less than 50. When examined by us at 13 years, his weight was 21 kg ( - 2.9 SD), height 122 cm ( - 4 . 4 SD), OFC 46 cm (-5.5 SD), arm span 126 cm. The following abnormalities were observed: microcephaly, a “coarse” face, facial hirsutism with low anterior hair line, mild synophrys, strabismus externus, crowded teeth, malformed ears, narrow shoulders, mild thoracic kyphosis, ventricular septa1 defect (spontaneously closed), bilateral cryptorchidism, a “buried” penis, long limbs compared to height, and digital and nail anomalies (Fig. 2). The digital anomalies, including abnormal roentgonographic findings, are shown in Table I. Dermatoglyphyic findings were nine arch and one whorl patterns and bilateral simian creases. The atd angles were normal bilaterally. Radiographic findings, other than those in hands and feet, included thoracic kyphosis, and lumbar lordosis, but no abnormal calcifications in the brain nor increased digital markings on the skull. An intravenous pyelogram was normal. Computerized tomography (CT) of the brain was normal. His carpal bone age was 11 years. Routine laboratory investigations, including blood chemistry and metabolic screening in the urine, showed normal results. The Giemsa trypsin-G (GTG) banded chromosomes were normal.
90
Tonoki et al.
I
I1
m Fig. 1. Family pedigree. 6 ,brachydactyly;
+, nail anomaly; @, mental retardation; @, dwarfism.
Patient 2 The younger brother of the propositus (Fig. 1, 111-8) was 11years old. He was born a t 41 weeks with a weight of 3,100 g, length 49 cm, and OFC 32 cm. In spite of good feeding, his growth was retarded. At age 13/12year, his weight was 6.5 kg; and at age 3 years, weight was 8.2 kg and height 80 cm (-4.0 SD). His carpal bone age at 28/12 years was estimated at 2 years. During the first 4 years of his life, mental retardation was not remarkable. When examined by us at age 11years, his height was 118 cm ( - 3.6 SD), weight 23 kg ( - 1.8SD), OFC 50 cm ( - 2.4 SD), arm span 112.5 cm, and I& 59. The following abnormalities was noted: microcephaly,a flat and round face, crowded teeth, overfolded ears, congenital muscular torticollis (correctedby operation at age 26/12 years), mild thoracic kyphosis, hydrocele of the testis and bilateral anomalies of fingers, toes and nails (Fig. 3). The digital anomalies, including abnormal roentgenographic findings, are shown in Table I. Dermatoglyphic findings were four arch patterns but no simian crease. The atd angles were normal. Skull roentgenography and the brain computed tomography (CT) and intravenous pyelography were normal. His carpal bone age was 11years. His GTG-banded chromosomes were nor-
mal. Routine laboratory investigations gave normal findings. The mother (Fig. 1,II-5) was born to unrelated, phenotypically normal parents. When seen by us, she was 37 years old, 144 cm tall ( - 2.6 SD), and a mentally dull woman. She had no digital anomalies except for hypoplastic nails. Her dermatoglyphic finding was seven arch patterns. Her face resembled that of her sons but was not “coarse.” She had no vertebral anomalies. A younger brother of the mother (Fig. 1, 11-61, who died of pneumonia a t age 17 years, was short and had severe mental retardation; he was 140 cm tall ( - 5.3 SD) at 17 years. Finger and nail anomalies were noted by his relatives but not examined in detail by us. His photographs suggested that his face was similar to that of the propositus. The mother’s sisters (Fig. 1, 11-1,2,4,7) were all 145-152 cm tall and other brothers (Fig. 1,II-3,8) were 165-170 cm tall. They all had normal intelligence and had no abnormalities in their faces,fingers, nails, and in the vertebrae. The father (Fig. 1,11-12)was 159 cm tall with normal intelligence, and his sibs were all normal. The first cousin of the propositus (Fig. 1, 111-2) suf-
TABLE I. Digital and Nail Anomalies by Inspection and Roentgenographic Studies of the Propositus and the Brother
Brachydacty ly Clinodactyl y Camptodactyly Partial syndactyly Broad fingers or toes Nail deformity Nail hypoplasia Nail defect Absent distal phalanx Short distal phalanx Short middle phalanx Phalangeal fusion
Affected digits in the propositus Fingers Toes ~Right Left Right Left
Affected digits in the brother Fingers Toes ~ _ _ _ _ _ _ Right Left Right ~Left
I1 V 11-v 111-IV
I1 V
I1 V 11-v
V
11-IV I
11-IV I
11-IV
11-111 I
1-111 I1
I I1
I1
I1
11-v 11-v
I1
I1 I1 111-v 11-v
~~
11-v 11-111
11-v I1
11-111 I
Dwarfism-Brachydactyly-Mental Retardation
91
Fig. 2. Propositus at age 13 years: Facial appearance (A),whole body (B), hands (C), hand roentgenogram (D), and feet (El.
fered from renal failure but had no clinical findings resembling to those of the propositus.
DISCUSSION The propositus had microcephalus, a coarse face, bilateral brachydactyly, nail anomalies, excess fingertip arch patterns, dwarfism, cryptorchidism, vertebral
anomalies, and severe mental retardation; his younger brother had similar manifestations without excess fingertip arch patterns, a coarse face, and cryptorchidism. However, the facial appearance of the sibs was similar. Brachydactyly of index fingers, a n interdigital webbing, broad first toes, partial syndactyly of toes, and clinodactyly of fifth fingers are common manifestations of both
92
Tonoki et al.
Fig, 3. The younger brother at age 11 years: Facial appearance (A), whole body (B), hands (C) hand roentgenogram (D), and feet (El.
sibs. Nails were affected more severely in the propositus than in the younger brother. Abnormal x-ray findings in their hands included the absence and/or shortness of the distal phalanx of fingers 11, distal phalanges of fingers 111-V, and middle phalanges of fingers 11-V, corresponding to the type B brachydactyly [Temtamy and McKusick, 19781, although the defects were not com-
pletely symmetrical. In addition, our patients had the following manifestations in common: dwarfism, microcephalus, characteristic face, vertebral anomalies, and mental retardation. To our knowledge, familial occurrence of the association of those abnormalities has not been reported previously. A number of malformation syndromes are known to
Dwarfism-Brachydactyly-MentalRetardation
represent type B brachydactyly [Temtamy and McKusick, 19781. Brachydactyly in Sorsby syndrome is similar to that in the present cases. However, macular coloboma and renal anomalies were not present in our patients. Likewise, Keutel syndrome, Larsen syndrome, and Berk-Tabatznik syndrome are also incompatible with the malformation complex seen in our patients. Coffin-Siris syndrome resembles the manifestations of our patients because of dwarfism, mental retardation, bushy eyebrows, microcephaly, retarded bone age, and onychodystrophy. However, the facial appearance and deformity in the little fingers of our patients differentiate this entity from Coffin-Siris syndrome. Rudiger syndrome is characterized by developmental failure, coarse face, short fingers, and hypoplastic nails with short middle phalanges and rudimentary distal phalanges, abnormal dermatoglyphic patterns, including bilateral simian creases and simple arches in all digits, thickened palms and soles, cleft soft palate, and ureteral stenosis [Rudiger et al., 19711. Although most of the manifestations observed in our patients are compatible with this syndrome, lack of thickening of palms and soles, cleft soft palate, and urinary tract anomalies, and difference in the face differentiate the malformation complex in our patients from this syndrome. Some other malformation syndromes representing miscellaneous types of brachydactyly must be discussed. Otopalatodigital (OPD) syndrome is a multiple congenital anomaly/mental retardation (MCA/MR) syndrome of mental retardation, small stature, cleft soft palate, small trunk, broad distal digits with short nails, limited elbow extension, characteristic face, and deafness [Bergsma, 19791. Although the manifestations of the propositus of our family seem similar, he had no hearing loss, limited extension of elbow, cleft palate, nor shortness of third to fifth metacarpals, concluding that he was not affected with OPD syndrome. F’reaxial brachydactyly, brachycamptodactyly syndrome, Leri pleonostenosis, and Robinow syndrome can readily be distinguished from the malformation complex of our patients on the basis of their respective manifestations. Recently, Kumar and Levick [1986] reported familial occurrence of type B brachydactyly and ectrodactyly. However, none of the affected patients in their report had any manifestations similar to our patients except for digital anomaly. Neither a new nail dysplasia syndrome reported by Cooks et al. [1985] nor a new brachydactyly syndrome reported by Pitt and Williams [1985] is compatible to the manifestations of our patients. Tonoki e t al. [1988] reported a new malformation syndrome with cryptomicrotia and short, stubby fingers with excess fingertip arch patterns in a mother and son. Increased arch patterns in dermatoglyphics and brachytelomesophalangy described in their report are similar to digital anomalies of patients in this report; however, a lack of mental and developmental delay is incompatible with findings in our patients. Several malformation syndromes of camptodactyly are newly published [Baraitser, 1982; Rozin et al., 1984; Khaldi et al., 19881. Camptodactyly is observed in our propositus;
93
however, many characteristic manifestations of our patients-such as brachydactyly, nail anomaly, and peculiar face-are absent in the patients in their reports. Maternal intake of anticonvulsants, including valproate during pregnancy, and TORCH syndrome may result in nail anomalies; however, the history during pregnancy and clinical examinations showed no evidence of these problems. Finally, these differential diagnoses suggest that the malformation complex in our sibs is a new clinical entity. The mother of the propositus in our family seemed to be affected because she had short stature, hypoplastic nails and mental deficiency. Although she had no brachydactyly, the existence of excess fingertip arch patterns suggests that she is mildly affected. It is most likely that the younger brother of the mother was also affected. Several genetic mechanisms are conceivable for the occurrence of the disorder in our family. Mental retardation, short stature, and brachydactyly may be attributable to the pleiotropic effect of a n autosomal dominant gene with variable expression that originates in either of the maternal grandparents. Because definitely affected individuals in this family are all males and the female who transmitted the gene to both her sons is mildly affected, a n X-linked semidominant mode of inheritance is a n alternative explanation.
ACKNOWLEDGMENTS The authors thank Dr. N. Matsuura, M.D., for referral of the family. REFERENCES Baraitser M (1982): A new camptodactyly syndrome. J Med Genet 19:40-43. Bergsma D (1979):Birth Defects Compendium. 2nded. New York: Alan R. Liss, Inc., for The National Foundation-March of Dimes. Cooks RG, Hertz M, Katznelson MBM, Goodman RM (1985):A new nail dysplasia syndrome with onychonychia and absence andior hypoplasia of distal phalanges. Clin Genet 27:85-91. Khaldi F, Bennaceur B, Hammou A, Hamza M, Gharbi HA (1988):An autosomal recessive disorder with retardation of growth, mental deficiency, ptosis, pectus excavatum and camptodactyly. Pediatr Radio1 18:432-435. Kumar D, Levick RK (1986): Autosomal dominant onychodystrophy and anonychia with type B brachydactyly and ectrodactyly. Clin Genet 30:219-225. Pitt P, Williams I(1985): A new brachydactyly syndrome with similarities to Julia Bell types B and E. J Med Genet 22:202-204. Rozin MM, Hertz M, Goodman RM (1984): A new syndrome with camptodactyly, joint contractures, facial anomalies, and skeltal defect: A case report and review of syndromes with camptodactyly. Clin Genet 26:342-355. Rudiger RA, Schmidt W, Loose DA, Passarge E (1971):Severe developmental failures, distal limb hypoplasia, thickened palmar creases, bifid uvula, and ureteral stenosis: A previously unidentified familial disorder with lethal outcome. J Pediatr 79:977-981. Temtamy S, Mckusick VA (1978):The Genetics of Hand Malformations. New York: Alan R. Liss, Inc., for The National Foundation-Marchof Dimes. BD:OAS XIV(3):187-299. Tonoki H, Ohura T, Niikawa N (1988): Cryptomicrotia and short stubby fingers with excess fingertip arch patterns in a mother and son. Am J Med Genet 29:857-862.
