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Classification of limb anomalies in oral-facial-digital syndromes
C L A S S I F I C A T I O N OF L I M B A N O M A L I E S I N ORAL-FACIAL-DIGITAL SYNDROMES M. M . A L - Q A T T A N and J . M . A. H A S S A N A I N
From the Division o f Plastic Surgery, King Saud University, Riyadh, Saudi Arabia
A classification of limb anomalies in oral-facial-digital (OFD) syndromes is offered to help differentiate between the various types of OFD syndromes. A clinical case is presented with clinical features consistent with both OFD syndrome type I (Papillon Leage--Psaume syndrome) and type VI (Vfiradi syndrome). The final diagnosis as a new mutation of type I syndrome was established after reviewing the radiological findings in the hands.
Journal of Hand Surgery (British and European Volume, 1997) 22B: 2." 250-252 limb anomalies of a syndrome are observed in all reported cases of that syndrome. Characteristic anomalies of a syndrome are not observed in all reported cases, but if present, they are pathognomonic for that syndrome. Constant and characteristic limb anomalies of the various OFD syndromes are shown in Table 1. Variable limb anomalies can be seen in any of the OFD syndromes and include brachydactyly, polydactyly, clinodactyly and/or syndactyly.
Oral-facial-digital (OFD) syndromes are a group of inherited syndromes that have in common anomalies of the tongue (bifid or lobulated tongue with hamartomas), the face (median cleft lip) and the digits (brachydactyly, polydactyly, clinodactyly and/or syndactyly). The striking heterogeneity among the various OFD syndromes makes the diagnosis of a specific syndrome a challenge (Baraitser, 1986; Gorlin et al, 1990; Haumont and Pelc, 1983; Martinot et al, 1994). In this paper, a classification of limb anomalies in OFD syndromes is offered. It is hoped that this classification will help differentiate between the various types of OFD syndromes, as is demonstrated in a clinical case report.
CASE REPORT The patient was a Saudi Arabian girl, born in 1995, as the sixth child of a 35-year-old mother and a 40-yearold father. The parents were not related and were healthy, as were the five older siblings. Pregnancy was uneventful and the infant was born after 40 weeks' gestation. Physical examination revealed the following abnormalities (Fig 1): milia of the face and ears, brittle-
CLASSIFICATION OF LIMB ANOMALIES IN OFD SYNDROMES Limb anomalies are classified into three groups: constant, characteristic and variable anomalies. Constant Table 1--Classification of limb anomalies in OFD syndromes
Type
Name of syndrome
Inheritance
Limb anomalies Constant
l
Papillon LeagePsaume syndrome
X-linked dominant (lethal in males) or new mutation
II
Mohr syndrome
III
V
Sugarman syndrome Baratser-Burn syndrome Thurston syndrome
Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive
VI
Vfiradi syndrome
Autosomal recessive
VII
Whelan syndrome
Autosomal or X-linked dominant
IV
Characteristic Fine reticular radiolucencies with spicule-like formation in the phalanges. The metacarpals may show oblique or irregular radiolucent lines and are generally dense.
Other main clinicalfeatures (in addition to cleft lip and lobulated tongue) Milia of the face and ears, brittle scalp hair with alopecia
Polysyndactyly of the big toe Continuous alternating winking of the eye lids Tibial dysplasia Bilateral postaxial polydactyly of hands and feet Forked third or fourth metacarpal.
Cerebellar anomalies Hydronephrosis, ear abnormalities
250
ORAL-FACIAL-DIGITAL SYNDROMES
Fig I
251
Clinical features: (a) milia of the face, median cleft of the upper lip and bifid tongue. Note the whitish hamartoma at the right lateral border of the tongue. (b) Brachydactyly. (c) Hand radiograph showing fine reticular radiolucencies with spicule-like formation in the phalanges (more apparent in the proximal and middle phalanges of the middle and ring fingers). The metacarpals are generally dense. An oblique radiolucent line is seen in the fourth metacarpal.
ness and dryness of the scalp hair with alopecia, median cleft of the upper lip, bifid tongue with hamartomas, thickened frenum, bilateral palatal grooves (dividing the palate into an anterior segment and two lateral palatal processes) and brachydactyly. No malformations of the cardiovascular, gastrointestinal or urinary systems were found. Ophthalmological findings were normal. Developmental delay and hypotonia were evident. Chromosomal analysis revealed a normal female karyotype. X-rays of the hands (Fig 1) showed fine reticular radiolucencies with spicule-like formation in the phalanges. The metacarpals were generally dense. X-rays of the feet showed no abnormalities. CT scan of the brain showed hypoplasia of the cerebellar hemispheres and vermis with an enlarged
cisterna magna in the posterior fossa. The patient was diagnosed as OFD syndrome type I (new mutation). DISCUSSION The case described in this paper had clinical features consistent with both OFD syndrome type I (milia of the face and ears, brittle scalp hair with alopecia) and type VI (cerebellar anomalies) (Table 1). The final diagnosis as a new mutation of type I OFD syndrome was established after reviewing the radiological findings of the hands and was based on the presence of reticular radiolucencies with spicule-like formation in the phalanges, and the absence of a forked metacarpal. Fine reticular radiolucencies with spicule-like formation in the phalanges and radiodense metacarpals with
252
irregular radiolucent lines have been reported by several authors in the type I syndrome and are considered pathognomonic for that syndrome (Anner6n et al, 1984; Gorlin et al, 1990; Rimoin and Edgerton, 1967; Stapleton et al, 1982; Wood et al, 1975). A striking radiological finding of OFD syndrome type VI, which has been observed in all cases thus far examined, is the presence of a forked third or fourth metacarpal (Gorlin et al, 1990; Mattei and Aym6, 1983; Munke et al, 1990; Vfiradi et al, 1980; Wey et al, 1994). The forked metacarpal is usually associated with central polydactyly. However, a forked metacarpal without an extra digit has been reported (Mattei and Aym6, 1983). For parent counselling purposes, a clinical differentation between OFD syndrome types I and VI is essential since the former is an X-linked dominant trait and lethal in the male while the latter is inherited as autosomal recessive. Thus, affected girls with OFD syndrome type I are mostly due to a new mutation with a very low recurrence risk, in contrast to the high recurrence risk in type VI (Munke et al, 1990). References Anner6n G, Arvidson B, Gustavson KH, Jorulf H, Carlsson G (1984). Orofacio-digital syndromes I and II: radiological methods for diagnosis and the clinical variations. Clinical Genetics, 26: 178-186.
T H E J O U R N A L OF H A N D S URGER Y VOL. 22B No. 2 APRIL 1997
Baraitser M (1986). The orofaciodigital (OFD) syndromes. Journal of Medical Genetics, 23: 116-119. Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck, 3rd Edn. New York, Oxford University Press, 1990:676 686. Haumont D, Pelc S (1983). The Molar syndrome: are there two variants? Clinical Genetics, 24:41 46. Martinot VL, Manouvrier S, Anastassov Y, Ribiere J, Pellerin PN (1994). Orodigitofacial syndromes type I and II: clinical and surgical studies. Cleft Palate--Craniofacial Journal, 31: 401-408. Mattei JF, Aym6 S (1983). Syndrome of polydactyly, cleft lip, lingual hamartomas, renal hypoplasia, hearing loss, and psychomotor retardation: variant of the Mohr syndrome or a new syndrome? Journal of Medical Genetics, 20: 433-435. Munke M, McDonald DM, Cronister A, Stewart JM, Gorlin R J, Zackai EH (1990). Oral-facial-digital syndrome type VI (Vfiradi syndrome): Further clinical delineation. American Journal of Medical Genetics, 35: 360-369. Rimoin DL, Edgerton MT (1967). Genetic and clinical heterogeneity in the oralfacial-digital syndromes. Journal of Pediatrics, 71: 94-102. Stapleton FB, Bernstein J, Koh G, Roy S, Wilroy RS (1982). Cystic kidneys in a patient with oral-facial-digital syndrome type I. American Journal of Kidney Diseases, 1: 288-293. Vfiradi V, Szab6 L, Papp Z (1980). Syndrome of polydactyly, cleft lip/palate or lingual lump and psychomotor retardation in endogamic gypsies. Journal of Medical Genetics, 17: 119-122. Wey PD, Neidich JA, Hoffman LA, LaTrenta GS (1994). Midline defects of the orofaciodigital syndrome type VI (Vfiradi syndrome). Cleft PalateCraniofacial Journal, 13: 397-400. Wood BP, Young LW, Townes PL (1975). Cerebral abnormalities in the oralfacial-digital syndrome. Pediatric Radiology, 3: 130-136.
Received: 28 May 1996 Accepted: 8 July 1996 Dr M. M. AI-Qattan, PO box 18097, Riyadh i 1415, Saudi Arabia. © 1997 The British Society for Surgery of the Hand
From the Division o f Plastic Surgery, King Saud University, Riyadh, Saudi Arabia
A classification of limb anomalies in oral-facial-digital (OFD) syndromes is offered to help differentiate between the various types of OFD syndromes. A clinical case is presented with clinical features consistent with both OFD syndrome type I (Papillon Leage--Psaume syndrome) and type VI (Vfiradi syndrome). The final diagnosis as a new mutation of type I syndrome was established after reviewing the radiological findings in the hands.
Journal of Hand Surgery (British and European Volume, 1997) 22B: 2." 250-252 limb anomalies of a syndrome are observed in all reported cases of that syndrome. Characteristic anomalies of a syndrome are not observed in all reported cases, but if present, they are pathognomonic for that syndrome. Constant and characteristic limb anomalies of the various OFD syndromes are shown in Table 1. Variable limb anomalies can be seen in any of the OFD syndromes and include brachydactyly, polydactyly, clinodactyly and/or syndactyly.
Oral-facial-digital (OFD) syndromes are a group of inherited syndromes that have in common anomalies of the tongue (bifid or lobulated tongue with hamartomas), the face (median cleft lip) and the digits (brachydactyly, polydactyly, clinodactyly and/or syndactyly). The striking heterogeneity among the various OFD syndromes makes the diagnosis of a specific syndrome a challenge (Baraitser, 1986; Gorlin et al, 1990; Haumont and Pelc, 1983; Martinot et al, 1994). In this paper, a classification of limb anomalies in OFD syndromes is offered. It is hoped that this classification will help differentiate between the various types of OFD syndromes, as is demonstrated in a clinical case report.
CASE REPORT The patient was a Saudi Arabian girl, born in 1995, as the sixth child of a 35-year-old mother and a 40-yearold father. The parents were not related and were healthy, as were the five older siblings. Pregnancy was uneventful and the infant was born after 40 weeks' gestation. Physical examination revealed the following abnormalities (Fig 1): milia of the face and ears, brittle-
CLASSIFICATION OF LIMB ANOMALIES IN OFD SYNDROMES Limb anomalies are classified into three groups: constant, characteristic and variable anomalies. Constant Table 1--Classification of limb anomalies in OFD syndromes
Type
Name of syndrome
Inheritance
Limb anomalies Constant
l
Papillon LeagePsaume syndrome
X-linked dominant (lethal in males) or new mutation
II
Mohr syndrome
III
V
Sugarman syndrome Baratser-Burn syndrome Thurston syndrome
Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive
VI
Vfiradi syndrome
Autosomal recessive
VII
Whelan syndrome
Autosomal or X-linked dominant
IV
Characteristic Fine reticular radiolucencies with spicule-like formation in the phalanges. The metacarpals may show oblique or irregular radiolucent lines and are generally dense.
Other main clinicalfeatures (in addition to cleft lip and lobulated tongue) Milia of the face and ears, brittle scalp hair with alopecia
Polysyndactyly of the big toe Continuous alternating winking of the eye lids Tibial dysplasia Bilateral postaxial polydactyly of hands and feet Forked third or fourth metacarpal.
Cerebellar anomalies Hydronephrosis, ear abnormalities
250
ORAL-FACIAL-DIGITAL SYNDROMES
Fig I
251
Clinical features: (a) milia of the face, median cleft of the upper lip and bifid tongue. Note the whitish hamartoma at the right lateral border of the tongue. (b) Brachydactyly. (c) Hand radiograph showing fine reticular radiolucencies with spicule-like formation in the phalanges (more apparent in the proximal and middle phalanges of the middle and ring fingers). The metacarpals are generally dense. An oblique radiolucent line is seen in the fourth metacarpal.
ness and dryness of the scalp hair with alopecia, median cleft of the upper lip, bifid tongue with hamartomas, thickened frenum, bilateral palatal grooves (dividing the palate into an anterior segment and two lateral palatal processes) and brachydactyly. No malformations of the cardiovascular, gastrointestinal or urinary systems were found. Ophthalmological findings were normal. Developmental delay and hypotonia were evident. Chromosomal analysis revealed a normal female karyotype. X-rays of the hands (Fig 1) showed fine reticular radiolucencies with spicule-like formation in the phalanges. The metacarpals were generally dense. X-rays of the feet showed no abnormalities. CT scan of the brain showed hypoplasia of the cerebellar hemispheres and vermis with an enlarged
cisterna magna in the posterior fossa. The patient was diagnosed as OFD syndrome type I (new mutation). DISCUSSION The case described in this paper had clinical features consistent with both OFD syndrome type I (milia of the face and ears, brittle scalp hair with alopecia) and type VI (cerebellar anomalies) (Table 1). The final diagnosis as a new mutation of type I OFD syndrome was established after reviewing the radiological findings of the hands and was based on the presence of reticular radiolucencies with spicule-like formation in the phalanges, and the absence of a forked metacarpal. Fine reticular radiolucencies with spicule-like formation in the phalanges and radiodense metacarpals with
252
irregular radiolucent lines have been reported by several authors in the type I syndrome and are considered pathognomonic for that syndrome (Anner6n et al, 1984; Gorlin et al, 1990; Rimoin and Edgerton, 1967; Stapleton et al, 1982; Wood et al, 1975). A striking radiological finding of OFD syndrome type VI, which has been observed in all cases thus far examined, is the presence of a forked third or fourth metacarpal (Gorlin et al, 1990; Mattei and Aym6, 1983; Munke et al, 1990; Vfiradi et al, 1980; Wey et al, 1994). The forked metacarpal is usually associated with central polydactyly. However, a forked metacarpal without an extra digit has been reported (Mattei and Aym6, 1983). For parent counselling purposes, a clinical differentation between OFD syndrome types I and VI is essential since the former is an X-linked dominant trait and lethal in the male while the latter is inherited as autosomal recessive. Thus, affected girls with OFD syndrome type I are mostly due to a new mutation with a very low recurrence risk, in contrast to the high recurrence risk in type VI (Munke et al, 1990). References Anner6n G, Arvidson B, Gustavson KH, Jorulf H, Carlsson G (1984). Orofacio-digital syndromes I and II: radiological methods for diagnosis and the clinical variations. Clinical Genetics, 26: 178-186.
T H E J O U R N A L OF H A N D S URGER Y VOL. 22B No. 2 APRIL 1997
Baraitser M (1986). The orofaciodigital (OFD) syndromes. Journal of Medical Genetics, 23: 116-119. Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck, 3rd Edn. New York, Oxford University Press, 1990:676 686. Haumont D, Pelc S (1983). The Molar syndrome: are there two variants? Clinical Genetics, 24:41 46. Martinot VL, Manouvrier S, Anastassov Y, Ribiere J, Pellerin PN (1994). Orodigitofacial syndromes type I and II: clinical and surgical studies. Cleft Palate--Craniofacial Journal, 31: 401-408. Mattei JF, Aym6 S (1983). Syndrome of polydactyly, cleft lip, lingual hamartomas, renal hypoplasia, hearing loss, and psychomotor retardation: variant of the Mohr syndrome or a new syndrome? Journal of Medical Genetics, 20: 433-435. Munke M, McDonald DM, Cronister A, Stewart JM, Gorlin R J, Zackai EH (1990). Oral-facial-digital syndrome type VI (Vfiradi syndrome): Further clinical delineation. American Journal of Medical Genetics, 35: 360-369. Rimoin DL, Edgerton MT (1967). Genetic and clinical heterogeneity in the oralfacial-digital syndromes. Journal of Pediatrics, 71: 94-102. Stapleton FB, Bernstein J, Koh G, Roy S, Wilroy RS (1982). Cystic kidneys in a patient with oral-facial-digital syndrome type I. American Journal of Kidney Diseases, 1: 288-293. Vfiradi V, Szab6 L, Papp Z (1980). Syndrome of polydactyly, cleft lip/palate or lingual lump and psychomotor retardation in endogamic gypsies. Journal of Medical Genetics, 17: 119-122. Wey PD, Neidich JA, Hoffman LA, LaTrenta GS (1994). Midline defects of the orofaciodigital syndrome type VI (Vfiradi syndrome). Cleft PalateCraniofacial Journal, 13: 397-400. Wood BP, Young LW, Townes PL (1975). Cerebral abnormalities in the oralfacial-digital syndrome. Pediatric Radiology, 3: 130-136.
Received: 28 May 1996 Accepted: 8 July 1996 Dr M. M. AI-Qattan, PO box 18097, Riyadh i 1415, Saudi Arabia. © 1997 The British Society for Surgery of the Hand