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Delayed appearance of left-sided diaphragmatic hernia in infancy
990
Brief clinical and laboratory observations
Table L N u m b e r s of alpha and beta cells in pancreatic sections of the patient and of 6 age-matched control subjects i
]No. alpha cells No. beta cells I Beta~alpha ratio I
Patient Controls
1789 622
1211 2378
0.68 3.82
weeks of life, and usually clear up spontaneously,I. ~ In the present case several factors may have contributed to the development of hyperglycemia. The usual predisposing factor, intrauterine growth retardation, was extreme. Glucose utilization by the small and malformed brain was presumably low. In anencephalic newborn infants insulin resistance is found, but the blood glucose levels are usually very stable and the only pancreatic abnormality described has been beta cell hyperplasia. ~ Unlike anencephalic infants, our patient had a macroscopically normal hypophysis and only later in the course of the disease developed resistance to exogenous insulin.
Delayed appearance of left-sided diaphragmatic hernia in infancy
The Journal of Pediatrics. June 1976
We consider that the most plausible explanation for the disturbance in carbohydrate metabolism was the pancreatic malformation, with a grossly reduced total mass and a significantly reduced proportion of beta to alpha cells in the islets.
REFERENCES 1. Gentz JCH, and Cornblath M: Transient diabetes of the newborn, Adv Pediatr 16:345, 1969. 2. Cotle E: Transient diabetes of the newborn, in Kelley VC, editor: Metabolic, endocrine and genetic disorders of children, vol. 2, New York, 1974, Harper & Row, Publishers, p 647. 3. Pagliara AS, Karl IE, and Kipnis DB: Transient neonatal diabetes: Delayed maturation of the pancreatic beta cells, J PEDIATR82:97, 1973. 4. Leisti J: Structural variation in human mitotic chromosomes, Ann Acad Sci Fenn [Biol] 179:13, 1971. 5. Allderdice PW, Davis JG, Miller O J, Klinger HP, Warburton D, Miller DA, Alle FJ Jr, Abrams CAL, and McGilvray E: The 13q- deletion syndrome, Am J Hum Genet 21:499, 1969. 6. Hayek A, Driscoll SG, and Warshaw JB: Endocrine studies in anencephaly, J Clin Invest 52:1636, 1973.
ties in diagnosis may arise w h e n the clinical pattern differs from the usual presentation in the neonatal period. The hernia may be mistaken for an acquired pleural or pulmonary disease. The first case in this report illustrates this point.
CASE REPORTS Lawrence W. Hurdiss, Major (MC) USA, San Francisco, Calif., Hooshang Taybi, M.D.,* and L. Morris Johnson, M.D., Oakland, Calif. A RELATIVELY UNCOMMON CAUSE of respiratory distress in the immediate postnatal period is the herniation of the abdominal viscera into the thorax through a congenital posterolateral diaphragmatic defect? Occasionally patients with this type of hernia will present later in life with respiratory or digestive symptoms. 1-7 DifficulFrom the Department of Radiology, Letterman Army Medical Center, Presidio of San Francisco, and the Departments of Radiology, and Surgery, Children's Hospital Medical Center, Oakland. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of'the Department of the Army or the Department of Defense. *Reprint address: Children's Hospital Medical Center, Oakland, Calif. 94609.
Case 1. A 3-month-old infant (F. W.), born of a normal pregnancy, was reported to have been apneic at birth for approximately 189 minutes after an initial weak cry at the perineum. The infant responded to bag and mask resuscitation. The chest roentgenogram at this time revealed no abnormality of diaphragm. The infant remained asymptomatic until one week prior to admission to Letterman Army Medical Center, when he became less active and had episodes of crying with flexion of his lower limbs toward the abdomen. At admission to the hospital the chest was reported to have been "clear without retraction." The abdomen was tense with a swollen area running diagonally from the left costal margin through the umbilical region. The clinical diagnosis at admission was bowel obstruction. A chest roentgenogram showed a density in the left lower hemithorax, which was initially interpreted as a loculated pleural effusion. A contrast study of the alimentary tract showed the density to be Bochdalek hernia with the midgut located in the thorax. At operation the cecum was found to be located in the midline on a long mesentery. The stomach and spleen were both intraabdominal. The posterolateral diaphragmatic defect was easily closed and no hernia sac was found. Postoperative recovery was uneventful.
Volume 88 Number 6
Brief cfinical and laboratory observations
99 1
Fig. 1A. (Case 2): There is no evidence of presence of diaphragmatic abnormality in the chest film obtained in the neonatal period. Case 2. A term male infant (J. H.), born after a normal pregnancy, appeared dusky shortly after birth. A chest roentgenogram demonstrated no evidence of presence of diaphragmatic hernia (Fig. 1A). Approximately one month prior to his admission to Children's Hospital Medical Center, at 91A months, he developed wheezes after a bout of "gastroenteritis," and for the next two weeks was noted to develop retractions and increased respiratory rate. A chest roentgenogram demonstrated a leftsided diaphragmatic hernia (Fig. 1B). The diagnosis was confirmed by a contrast study of the alimentary tract. At operation the entire midgut and colon to the level of the splenic flexure were within the thorax via a left posterolateral diaphragmatic defect. The stomach and spleen were in the abdomen. A hernia sac was not found. The defect was closed; postoperative recovery was uneventful.
DISCUSSION F r o m m and Lucas 5 have stated that a previously normal chest roentgenogram precludes the possibility of congenital Bochdalek hernia. The recent literature on this subject challenges this statement. Canino and associates, 2 Faur6 and associates, 4 Forshall, ~ Kirschner and associates 7 have reported a total of eight patients with rightsided Bochdalek hernia that appeared after previously normal chest roentgenograms had been obtained. Day ~ has reported a left-sided Bochdalek hernia in a 5-year-old child who had a normal chest roentgenogram prior to a surgical procedure for diversion of the urinary tract to an ileal loop. Glasson and associates ~ have examined and treated three infants with congenital left posterolateral diaphragmatic hernia who had previously normal chest roentgenograms. A case reported by Dutta, 9 as sponta-
Fig, lB. Same at 9% months of age. Herniation of the bowel into the left hemithorax is present.
neous rupture of diaphragm due to pertussis, may have had an anomalous diaphragm. A hernia sac was not found in either of our two infants, nor was history of trauma elicited. The appearance of the diaphragm under direct inspection, and the associated anomalies were typical of congenital defect. The diaphragmatic defect in these infants is considered to be congenital, whereas the herniation may not occur until some mechanical or pressure changes in the thoracoabdominal cavities take place. Increased intra-abdominal pressure, such as in bowel distension, may play a major role in causation of herniation. The liver for a time may prevent the right-sided herniation. The spleen may exert a similar role on. the left side. REFERENCES
1. Firestone FN, Popper RW, Taybi H, and Leonards R: Congenital diaphragmatic hernia and hypoplastic left heart. A case report and discussion, Pediatrics 40:329, 1967. 2. Canino CW, Eichman J, Rominger CJ, and Ryan JJ: Congenital right diaphragmatic hernia, Radiology 82:249, 1964. 3. Day B: Late appearance of Bochdalek hernia, Br Med J 1:786; 1972. 4. Faur6 C, Sauvegrain J, and Bomsel F: Right-sided congenital diaphragmatic hernia with delayed radiological manifestations, Ann Radio1 14:305, 1971. 5. Fromm SH, and Lucas CE: An unusual complication of chronic diaphragmatic hernia in an adult patient, J Thorac Cardiovasc Surg 61:654, 1971.
992
6.
7.
8.
B r i e f clinical a n d laboratory observations
The Journal of Pediatrics June 1976
Glasson MJ, Barter W, Cohen DH, and Bowdler JD: Congenital left posterolateral diaphragmatic hernia with previously normal chest x-ray, Pediatr Radiol 3:201, 1975. Kirschner SG, Burko H, O'Neill JA Jr, and Stahlman M: Delayed radiographic presentation o f congenital right diaphragmatic hernia, Radiology 115:155, 1975. Forshall I: Less common herniae through the diaphragm of infants and children, Proc R Soc Med 59:212, 1966.
Familial anal abnormality Ian S. Reid, F.R.C.S,(E.), F.R.A.C.S.,* Camperdown, N . S . W . , Australia, and
Gilllan Turner, F.R.C.P.(C.), M.R.C.P.(E.), Randwick, N.S. W., Australia
A S K I N - C O V E R E D ANUS is a relatively c o m m o n , easily correctible f o r m o f anal atresia o c c u r r i n g chiefly in t h e male. A n t e r i o r p o s i t i o n i n g o f t h e anus is also relatively c o m m o n , m a y b e c o m p l e t e l y a s y m p t o m a t i c , a n d is f o u n d a l m o s t exclusively in t h e f e m a l e . It h a s b e e n s u g g e s t e d t h a t t h e s e two a n o m a l i e s m a y result f r o m
a similar
d e v e l o p m e n t a l error. It m i g h t b e e x p e c t e d t h e r e f o r e that familial cases o f this e r r o r w o u l d have a d i f f e r e n t e x p r e s sion in t h e two sexes. T h e f a m i l y d e s c r i b e d in this r e p o r t s h o w s a d o m i n a n t mode
of inheritance
of
anal
abnormality
which
is
e x p r e s s e d differently in the t w o sexes a n d varies in severity. FAMILY
HISTORY
The family tree is shown in Fig. 1. The propositus (IV.2) was referred to this hospital with a skin-covered anus and soon afterward his first cousin once removed (III.30) was seen withthe same lesion. A family history revealed that there were other affected members who had also been treated for skin-covered anus. Branches of this family agreed to be examined by us. The propositus was born after a normal term pregnancy. He was delivered by elective cesarian section because his mother had a third-degree tear after the birth of her first child. At six weeks of age he developed abdominal distension and was irritable. Examination of his perineum showed a prominent median raphe
From the Children's Medical Research Foundation, Royal Alexandra Hospital for Children, and Prihce of Wales Hospital. lan S. Reid is a James Fairfax Surgical Research Fellow. *Reprint address: Children's Medical Research Foundation, P.O. Box 61, Camperdown, N.S.W. 2050, Australia.
9.
10.
Dutta T: Spontaneous rupture of diaphragm due to pertussis, J Pediatr Surg 10"147, 1975. Treheux A, Bretagne MC, Rothahn B, Mourot M, and Prevot J: Pathologie malformative majeure du diaphragme a revelation tardive chez l'enfant, Ann Pediatr 21:765, 1974.
running backward from his scrotum and ending at the mouth of a fistula which tracked posteriorly to the normal anal position, where the skin was heaped up and completely covered the anus. The genitals were normal, and general physical examination revealed no other abnormality except bilateral preauricular skin tags and broad thumbs. At operation the fistulous tract was found to be 2 cm in length and led to a normal anal opening. The patient made an uneventful recovery. His mother (III.3) and his half-sister (IV.I) were found to have anteriorly placed anuses (Fig. 2). Six rfionths after the propositus was treated, Patient III.30 was admitted at one day of age; he had a completely skin-covered anus with no tract, broad thumbs, and preauricular skin tags. At operation a normal anal opening was observed with a mucosal membrane bulging through it. The latter was incised and sutured to the skin edges. Hospital records showed that his two elder brothers had been operated on for a similar condition. Patient III.28 was referred to this hospital when 2 days old with a skincovered anus and a fistulous.tract, and Patient III.29 was referred at 1 day of age with a skin-covered anus and a fistulous tract which had not perforated and ran anteriorly onto the scrotum. Each of them had preauricular skin tags and broad thumbs. Physical examination was carried out on the majority of the other members of this family as shown in the family tree. Six of the male members (II. 1, II.6, II. 13, III. 16, III.23, and III.24) were found to have an anus which was in the normal position but had an abnormal appearance. The skin around the edges was heaped up and the median raphe abnormally prominent (Fig. 3). Two of the males (I.2 and II.6) had had "hemorroidectomy" for anal irritation presumably resulting from the excessive skin around the anus. Patient III.1, who died in a motor vehicle accident, was also presumably affected, because he had required anal dilatation as an infant. The heaping up of the anal skin edges was not seen in any of the affected females. Five of the females (II. 11, III. 15, lIl. 17, 1II.22, and IV. 1) were found to have anteriorly placed anuses. Patient III.14 had been referred'to this hospital at the age of 3 months for constipation. Records confirmed that on examination her anus was reported to be anteriorly placed and stenotic. A cut-back procedure provided a satisfactory result. Two other members of this family had congenital anomalies. Patient III. 16 had a bifid thumb that required surgical correction, and Patiel~t III.25 had a cleft lip and palate which was repaired.
Brief clinical and laboratory observations
Table L N u m b e r s of alpha and beta cells in pancreatic sections of the patient and of 6 age-matched control subjects i
]No. alpha cells No. beta cells I Beta~alpha ratio I
Patient Controls
1789 622
1211 2378
0.68 3.82
weeks of life, and usually clear up spontaneously,I. ~ In the present case several factors may have contributed to the development of hyperglycemia. The usual predisposing factor, intrauterine growth retardation, was extreme. Glucose utilization by the small and malformed brain was presumably low. In anencephalic newborn infants insulin resistance is found, but the blood glucose levels are usually very stable and the only pancreatic abnormality described has been beta cell hyperplasia. ~ Unlike anencephalic infants, our patient had a macroscopically normal hypophysis and only later in the course of the disease developed resistance to exogenous insulin.
Delayed appearance of left-sided diaphragmatic hernia in infancy
The Journal of Pediatrics. June 1976
We consider that the most plausible explanation for the disturbance in carbohydrate metabolism was the pancreatic malformation, with a grossly reduced total mass and a significantly reduced proportion of beta to alpha cells in the islets.
REFERENCES 1. Gentz JCH, and Cornblath M: Transient diabetes of the newborn, Adv Pediatr 16:345, 1969. 2. Cotle E: Transient diabetes of the newborn, in Kelley VC, editor: Metabolic, endocrine and genetic disorders of children, vol. 2, New York, 1974, Harper & Row, Publishers, p 647. 3. Pagliara AS, Karl IE, and Kipnis DB: Transient neonatal diabetes: Delayed maturation of the pancreatic beta cells, J PEDIATR82:97, 1973. 4. Leisti J: Structural variation in human mitotic chromosomes, Ann Acad Sci Fenn [Biol] 179:13, 1971. 5. Allderdice PW, Davis JG, Miller O J, Klinger HP, Warburton D, Miller DA, Alle FJ Jr, Abrams CAL, and McGilvray E: The 13q- deletion syndrome, Am J Hum Genet 21:499, 1969. 6. Hayek A, Driscoll SG, and Warshaw JB: Endocrine studies in anencephaly, J Clin Invest 52:1636, 1973.
ties in diagnosis may arise w h e n the clinical pattern differs from the usual presentation in the neonatal period. The hernia may be mistaken for an acquired pleural or pulmonary disease. The first case in this report illustrates this point.
CASE REPORTS Lawrence W. Hurdiss, Major (MC) USA, San Francisco, Calif., Hooshang Taybi, M.D.,* and L. Morris Johnson, M.D., Oakland, Calif. A RELATIVELY UNCOMMON CAUSE of respiratory distress in the immediate postnatal period is the herniation of the abdominal viscera into the thorax through a congenital posterolateral diaphragmatic defect? Occasionally patients with this type of hernia will present later in life with respiratory or digestive symptoms. 1-7 DifficulFrom the Department of Radiology, Letterman Army Medical Center, Presidio of San Francisco, and the Departments of Radiology, and Surgery, Children's Hospital Medical Center, Oakland. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of'the Department of the Army or the Department of Defense. *Reprint address: Children's Hospital Medical Center, Oakland, Calif. 94609.
Case 1. A 3-month-old infant (F. W.), born of a normal pregnancy, was reported to have been apneic at birth for approximately 189 minutes after an initial weak cry at the perineum. The infant responded to bag and mask resuscitation. The chest roentgenogram at this time revealed no abnormality of diaphragm. The infant remained asymptomatic until one week prior to admission to Letterman Army Medical Center, when he became less active and had episodes of crying with flexion of his lower limbs toward the abdomen. At admission to the hospital the chest was reported to have been "clear without retraction." The abdomen was tense with a swollen area running diagonally from the left costal margin through the umbilical region. The clinical diagnosis at admission was bowel obstruction. A chest roentgenogram showed a density in the left lower hemithorax, which was initially interpreted as a loculated pleural effusion. A contrast study of the alimentary tract showed the density to be Bochdalek hernia with the midgut located in the thorax. At operation the cecum was found to be located in the midline on a long mesentery. The stomach and spleen were both intraabdominal. The posterolateral diaphragmatic defect was easily closed and no hernia sac was found. Postoperative recovery was uneventful.
Volume 88 Number 6
Brief cfinical and laboratory observations
99 1
Fig. 1A. (Case 2): There is no evidence of presence of diaphragmatic abnormality in the chest film obtained in the neonatal period. Case 2. A term male infant (J. H.), born after a normal pregnancy, appeared dusky shortly after birth. A chest roentgenogram demonstrated no evidence of presence of diaphragmatic hernia (Fig. 1A). Approximately one month prior to his admission to Children's Hospital Medical Center, at 91A months, he developed wheezes after a bout of "gastroenteritis," and for the next two weeks was noted to develop retractions and increased respiratory rate. A chest roentgenogram demonstrated a leftsided diaphragmatic hernia (Fig. 1B). The diagnosis was confirmed by a contrast study of the alimentary tract. At operation the entire midgut and colon to the level of the splenic flexure were within the thorax via a left posterolateral diaphragmatic defect. The stomach and spleen were in the abdomen. A hernia sac was not found. The defect was closed; postoperative recovery was uneventful.
DISCUSSION F r o m m and Lucas 5 have stated that a previously normal chest roentgenogram precludes the possibility of congenital Bochdalek hernia. The recent literature on this subject challenges this statement. Canino and associates, 2 Faur6 and associates, 4 Forshall, ~ Kirschner and associates 7 have reported a total of eight patients with rightsided Bochdalek hernia that appeared after previously normal chest roentgenograms had been obtained. Day ~ has reported a left-sided Bochdalek hernia in a 5-year-old child who had a normal chest roentgenogram prior to a surgical procedure for diversion of the urinary tract to an ileal loop. Glasson and associates ~ have examined and treated three infants with congenital left posterolateral diaphragmatic hernia who had previously normal chest roentgenograms. A case reported by Dutta, 9 as sponta-
Fig, lB. Same at 9% months of age. Herniation of the bowel into the left hemithorax is present.
neous rupture of diaphragm due to pertussis, may have had an anomalous diaphragm. A hernia sac was not found in either of our two infants, nor was history of trauma elicited. The appearance of the diaphragm under direct inspection, and the associated anomalies were typical of congenital defect. The diaphragmatic defect in these infants is considered to be congenital, whereas the herniation may not occur until some mechanical or pressure changes in the thoracoabdominal cavities take place. Increased intra-abdominal pressure, such as in bowel distension, may play a major role in causation of herniation. The liver for a time may prevent the right-sided herniation. The spleen may exert a similar role on. the left side. REFERENCES
1. Firestone FN, Popper RW, Taybi H, and Leonards R: Congenital diaphragmatic hernia and hypoplastic left heart. A case report and discussion, Pediatrics 40:329, 1967. 2. Canino CW, Eichman J, Rominger CJ, and Ryan JJ: Congenital right diaphragmatic hernia, Radiology 82:249, 1964. 3. Day B: Late appearance of Bochdalek hernia, Br Med J 1:786; 1972. 4. Faur6 C, Sauvegrain J, and Bomsel F: Right-sided congenital diaphragmatic hernia with delayed radiological manifestations, Ann Radio1 14:305, 1971. 5. Fromm SH, and Lucas CE: An unusual complication of chronic diaphragmatic hernia in an adult patient, J Thorac Cardiovasc Surg 61:654, 1971.
992
6.
7.
8.
B r i e f clinical a n d laboratory observations
The Journal of Pediatrics June 1976
Glasson MJ, Barter W, Cohen DH, and Bowdler JD: Congenital left posterolateral diaphragmatic hernia with previously normal chest x-ray, Pediatr Radiol 3:201, 1975. Kirschner SG, Burko H, O'Neill JA Jr, and Stahlman M: Delayed radiographic presentation o f congenital right diaphragmatic hernia, Radiology 115:155, 1975. Forshall I: Less common herniae through the diaphragm of infants and children, Proc R Soc Med 59:212, 1966.
Familial anal abnormality Ian S. Reid, F.R.C.S,(E.), F.R.A.C.S.,* Camperdown, N . S . W . , Australia, and
Gilllan Turner, F.R.C.P.(C.), M.R.C.P.(E.), Randwick, N.S. W., Australia
A S K I N - C O V E R E D ANUS is a relatively c o m m o n , easily correctible f o r m o f anal atresia o c c u r r i n g chiefly in t h e male. A n t e r i o r p o s i t i o n i n g o f t h e anus is also relatively c o m m o n , m a y b e c o m p l e t e l y a s y m p t o m a t i c , a n d is f o u n d a l m o s t exclusively in t h e f e m a l e . It h a s b e e n s u g g e s t e d t h a t t h e s e two a n o m a l i e s m a y result f r o m
a similar
d e v e l o p m e n t a l error. It m i g h t b e e x p e c t e d t h e r e f o r e that familial cases o f this e r r o r w o u l d have a d i f f e r e n t e x p r e s sion in t h e two sexes. T h e f a m i l y d e s c r i b e d in this r e p o r t s h o w s a d o m i n a n t mode
of inheritance
of
anal
abnormality
which
is
e x p r e s s e d differently in the t w o sexes a n d varies in severity. FAMILY
HISTORY
The family tree is shown in Fig. 1. The propositus (IV.2) was referred to this hospital with a skin-covered anus and soon afterward his first cousin once removed (III.30) was seen withthe same lesion. A family history revealed that there were other affected members who had also been treated for skin-covered anus. Branches of this family agreed to be examined by us. The propositus was born after a normal term pregnancy. He was delivered by elective cesarian section because his mother had a third-degree tear after the birth of her first child. At six weeks of age he developed abdominal distension and was irritable. Examination of his perineum showed a prominent median raphe
From the Children's Medical Research Foundation, Royal Alexandra Hospital for Children, and Prihce of Wales Hospital. lan S. Reid is a James Fairfax Surgical Research Fellow. *Reprint address: Children's Medical Research Foundation, P.O. Box 61, Camperdown, N.S.W. 2050, Australia.
9.
10.
Dutta T: Spontaneous rupture of diaphragm due to pertussis, J Pediatr Surg 10"147, 1975. Treheux A, Bretagne MC, Rothahn B, Mourot M, and Prevot J: Pathologie malformative majeure du diaphragme a revelation tardive chez l'enfant, Ann Pediatr 21:765, 1974.
running backward from his scrotum and ending at the mouth of a fistula which tracked posteriorly to the normal anal position, where the skin was heaped up and completely covered the anus. The genitals were normal, and general physical examination revealed no other abnormality except bilateral preauricular skin tags and broad thumbs. At operation the fistulous tract was found to be 2 cm in length and led to a normal anal opening. The patient made an uneventful recovery. His mother (III.3) and his half-sister (IV.I) were found to have anteriorly placed anuses (Fig. 2). Six rfionths after the propositus was treated, Patient III.30 was admitted at one day of age; he had a completely skin-covered anus with no tract, broad thumbs, and preauricular skin tags. At operation a normal anal opening was observed with a mucosal membrane bulging through it. The latter was incised and sutured to the skin edges. Hospital records showed that his two elder brothers had been operated on for a similar condition. Patient III.28 was referred to this hospital when 2 days old with a skincovered anus and a fistulous.tract, and Patient III.29 was referred at 1 day of age with a skin-covered anus and a fistulous tract which had not perforated and ran anteriorly onto the scrotum. Each of them had preauricular skin tags and broad thumbs. Physical examination was carried out on the majority of the other members of this family as shown in the family tree. Six of the male members (II. 1, II.6, II. 13, III. 16, III.23, and III.24) were found to have an anus which was in the normal position but had an abnormal appearance. The skin around the edges was heaped up and the median raphe abnormally prominent (Fig. 3). Two of the males (I.2 and II.6) had had "hemorroidectomy" for anal irritation presumably resulting from the excessive skin around the anus. Patient III.1, who died in a motor vehicle accident, was also presumably affected, because he had required anal dilatation as an infant. The heaping up of the anal skin edges was not seen in any of the affected females. Five of the females (II. 11, III. 15, lIl. 17, 1II.22, and IV. 1) were found to have anteriorly placed anuses. Patient III.14 had been referred'to this hospital at the age of 3 months for constipation. Records confirmed that on examination her anus was reported to be anteriorly placed and stenotic. A cut-back procedure provided a satisfactory result. Two other members of this family had congenital anomalies. Patient III. 16 had a bifid thumb that required surgical correction, and Patiel~t III.25 had a cleft lip and palate which was repaired.