 |
       |
|
|
CASE REPORTS
Fraser's Syndrome A Rare Congenital Anomaly
Ashok Kumar Shukla, Vaideha Desphande, Asha R Dalal
Mrs. SAK 26 years old married housewife unregistered, uninvestigated primigravida with 7 months amenorrhea came to the labour room with labour pain and preterm premature rupture of membranes since 2 hours. She delivered 1.2 kg baby which was found to have multiple congenital anomalies. Baby was resuscitated but died 2 hours after birth. Clinical examination findings and postmortem examination suggested that the baby had Fraser’s syndrome (Cryptophthalmos syndrome) a very rare syndrome. (Cryptophthalmos means hidden eye, fundamentally means absence of the palpebral fissure but usually includes varying absence of eyelashes and eyebrows and defects of the eye, especially the anterior part).
INTRODUCTION
Fraser syndrome (cryptophthalmos syndrome) is a rare autosomal recessive disorder.1 It combines acrofacial and urogenital malformations with or without cryptophthalmos. These anomalies were first documented by Fraser in 1962.2 The four major characteristics are cryptophthalmos, syndactyly, genital anomalies and affected siblings and eight minor characteristics are alterations of the nose, ears, larynx, oral clefts, umbilical hernia, renal agenesis (bilateral or unilateral), skeletal anomalies and mental retardation are part of the diagnosis of Fraser syndrome.1 Incidence: 0.043:10,000 liveborn infants and 1.1 : 10,000 stillbirths. Probably autosomal recessive since an unusual proportion of infants is born to consanguineous parents.2 Till now only 95 cases have been documented worldwide. Except genetic counselling there is no known method of prevention. Prognosis of such babies are poor and if they survive no clear prognosis regarding degree of mental retardation can be given.
CASE REPORT
Mrs SAK 26 years old housewife unregistered, uninvestigated primigravida with 7 months amenorrhoea came to labour room with complains of labour pains and preterm premature rupture of membranes since 2 hours. On examination she was vitally stable. Per abdomen she was 28 wks cephalic presentation foetal heart sounds were present with good uterine activity of 2-3/10/30. On per vaginal examination she was0 fully dilated fully effaced vertex presentation and membranes absent. She delivered vaginally without any difficulty a 1.2 kg child who cried immediately after birth with Apgar of 8,9,9. On examination baby was found to have multiple congenital malformations such as complete cryptophthalmos in the left eye with no eyelashes or eyebrows, and the skin passed unbroken from the brow to cheek (Fig. 1), partial cutaneous soft tissue syndactyly of all fingers and toes and ambiguous genitalia (Fig. 2).
Baby died 2 hours after birth. Postmortem examination showed patent ductus arteriosus and bilateral absent kidneys. Cause of death after postmortem was given as death due to asphyxia neonatorum in a preterm with multiple congenital anomalies (natural). Later patient gave history of marriage with her first cousin and she took discharge on request on day 2 of delivery.
DISCUSSION
Fraser’s syndrome is an autosomal recessive inherited syndrome.1 The parents of affected children are sometime, but not always consanguineous. The exact aetiopathogenesis is not known. Till now only 95 cases have been reported worldwide. The findings in this newborn are compatible with the diagnosis of cryptophthalmos syndrome according to the diagnostic criteria proposed by Thomas et al.1 The diagnosis is suggested if the patient has at least two major criteria and one minor criterion, or one major criterion and four minor criteria. The four major characteristics of Fraser’s syndrome are cryptophthalmos, syndactyly, genital anomalies and affected siblings and eight minor characteristics alterations of the nose, ears, larynx, oral clefts, umbilical hernia, renal agenesis (bilateral or unilateral), skeletal anomalies and mental retardation.1 This case satisfies 3 major criteria and 3 minor criteria. The major criteria are cryptophthalmos, syndactyly, abnormal genitalia, and the minor criteria are congenital malformation of ears, nose, bilateral renal agenesis.
This syndrome is recognised at birth by partial cutaneous syndactyly, genital malformation usually hypospadias, renal malformation, cryptophthalmos is usually but not always present.2,3 Hair growth pattern may be abnormal. Hearing is usually normal.4 Usually these babies are still born or die few hours after birth.5 If renal agenesis is present nothing can be done but genital, digital and cryptophthalmos can be surgically corrected if there are no ocular malformation.6,7 It is important to differentiate between isolated cryptophthalmos and cryptophthalmos syndrome. In the review by Thomas et al of 124 cases identified in the literature, 86 fulfilled the criteria for the diagnosis of cryptophthalmos syndrome, 27 were classified as isolated cryptophthalmos, and 11 remained unclassified. The majority of cases were familial and the remaining were sporadic. They reported that consanguinity was found in families with more than one affected child. There was no evidence of vertical transmission, although the features are strongly suggestive of autosomal recessive inheritance. Antenatal ultrasound finding as early as 18 weeks of gestation has been suggested to help in making the diagnosis of Fraser syndrome for possible termination of pregnancy, particularly in families with affected siblings. Schauer et al8 have found that antenatal renal agenesis, orbital abnormalities and increased thoracic volume are characteristic manifestations of Fraser syndrome. Further, Fryns et al9 reported that Fraser syndrome should be seriously considered if antenatal ultrasound shows oligohydramnios sequence with contrastingly voluminous, hyperechogenic lungs. Their explanation for the contradiction between oligohydramnios and voluminous hyperechogenic lungs in the presence of renal agenesis was that it was due to overdistended lungs, and the occurrence of non-immune hydrops foetalis secondary to laryngeal stenosis.
REFERENCES
1. Thomas IT, et al. Isolated and syndromic cryptophthalmos. Am J Med Gent 1986; 25 : 85.
2. Fraser GR. Our genetical load : a review of some aspect of genetical variation. Ann Hum Genet 1962; 25 : 387-415.
3. Codere F, Brownstein S, Chen MF. Cryptophthalmos syndrome with bilateral renal agenesis. Am J Ophthalmol 1981; 91 : 737.
4. Gattuso J, et al. The clinical spectrum of the Fraser syndrome: Report of three new cases and review. J Med Genet 1987; 24 : 549.
5. Schauer GM, Dunn LK, Godmilow L, Eagle Jr RC, Knisley AC. Prenatal diagnosis and Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks. Am J Med Genet 1990; 37 : 583-91.
6. Ford GR, et al. ENT manifestations of Fraser syndrome. J Laryngol Otol 1992; 106 : 1.
7. Kantaputra PN, Eiumtrakul P, Matin T, Opastirakul S, Visrutaratna P, Mevate U. Cryptophthalmos, dental and oral abnormalities, and brachymesophalangy of second toes: New syndrome of Fraser syndrome? Am J Med Gene 2001; 98 (3) : 263-8.
8. Schauer GM, Dunn LK, Godmilow L, Eagle Jr RC, Knisley AC. Prenatal diagnosis and Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks. Am J Med Genet 1990; 37 : 583-91.
9. Fryns JP, Schoubroeck DV, Vandenberche K, et al. Diagnostic echographic findings in cryptophthalmos syndrome (Fraser syndrome). Prenat Diagn 1997; 17 : 582-4.
LOW-DOSE BUDESONIDE FOR ASTHMA
Romain Pauwels and colleagues report results from a study in which patients with mild persistent asthma for less than 2 years, and not taking a glucocorticoid regularly, were given low-dose budesonide or placebo for 3 years. The study was randomised, double-blind, and large, with over 7000 patients from 32 countries.
The investigators found a reduction in exacerbations and need for oral and systemic steroids in the budesonide group and an improvement in asthma control.
The study has strengths and weaknesses. Strengths include the large size, and the pragmatic design means that it is looking at the effectiveness of the intervention and the findings should be generalisable. Weaknesses include the high number of dropouts.
The other interesting outcome is that there was a reduction in growth in children taking budesonide, of 0.43 cm a year. The reduction was similar in young children taking 200 µg daily or older children taking 400 µg daily. Final height is unlikely to be affected with these small doses but it is a timely reminder that doses of budesonide as low as 200 µg daily have measurable systemic effects. Higher doses will inevitably have greater effects and optimising the dose is clearly important and highlighted in the new asthma guidelines.
Anne E Tattersfiled, Tim W Harrison, Lancet; March, 2003; 29 : 1066-67.
 |