Absent iris stroma, narrow body build and small facial bones: a new association or variant of SHORT syndrome?

We report four patients from two unrelated families with strikingly similar facial appearance, short stature, narrow body build and, in two of the patients, abnormalities of the iris stroma. The birth of an affected offspring suggests that this syndrome is likely to have autosomal dominant inheritance. The facial appearance and some of the features resemble the SHORT syndrome, the name being an acronym for Short stature, Hyperextensible joints, Ocular depression, Rieger anomaly and abnormalities of the Teeth. The relationship of the syndrome to the SHORT syndrome is discussed.

Retinopathy of prematurity in infants weighing 1000-1499 g at birth.

OBJECTIVE: To review the incidence and severity of retinopathy of prematurity (ROP) in infants with birthweights 1000-1249 g and 1250-1499 g, to establish whether the upper weight limit for routine ophthalmological examination might safely be lowered. METHODOLOGY: Prospective cohort study of infants born between 1 January 1977 and 31 December 1992 cared for in the neonatal nurseries at the Royal Women's Hospital, Melbourne. Data were retrieved on 1373 infants who survived their initial hospitalization. They comprised 657 with birthweights 1000-1249 g (group 1) and 716 with birthweights 1250-1499 g (group 2). There were 76 outborn infants in group 1 and 97 in group 2; the remaining infants were all born at the Royal Women's Hospital. Ocular examinations commenced at 2 weeks of age, when possible, and at 2-weekly intervals after that. RESULTS: In group 1, ROP was detected in 14.6% (96/657) and severe ROP (bilateral stage 3-5) in 5.0% (33/657). Five (0.8%) children required surgical intervention (reaching threshold disease); following surgery, one was legally blind, one had severely impaired vision, and the other three had near-normal vision. Another child was blind; he was born at 28 weeks gestational age with a birthweight of 1170 g, and was transferred to a Level II hospital at 9 weeks chronological age with no detectable retinopathy. He returned 1 year later totally blind with detached retinae (grade 5 ROP). The prevalence of bilateral blindness in this group was 0.3% (2/657). In group 2, ROP was detected in 6.4% (46/716) and severe ROP in 0.8% (6/716). No children required surgery; three were found to be myopic at follow-up but the corrected visual acuity was normal. No children in group 2 were blind. No significant difference was found between the rates of ROP in inborn and outborn infants. CONCLUSION: In neonatal units with similar rates of ROP and visual outcome, routine ophthalmological examination in the neonatal nursery of infants weighing more than 1249 g at birth is probably unnecessary.

Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.

We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Retinopathy of prematurity in extremely low birth weight infants.

OBJECTIVE: To review the survival rate, the incidence and severity of retinopathy of prematurity (ROP), and the rate of blindness caused by ROP in extremely low birth weight (ELBW, birth weight 500 to 999 g) infants born between January 1, 1977, and December 31, 1992, and to determine whether increasing survival rates of ELBW infants are accompanied by an increase in the rates of severe ROP or blindness. DESIGN: Prospective cohort study of ELBW infants. Survival rates and visual outcomes were contrasted between children born in successive 8-year periods (1977 through 1984 and 1985 through 1992, inclusive). SETTING: The premature nurseries at the Royal Women's Hospital, Melbourne, a level-3 perinatal center. PATIENTS: Of 1001 inborn ELBW infants over the 16-year period, 457 (45.7%) survived their initial hospitalization: of the survivors, 434 (95.0%) were examined by the ophthalmologist, starting at 2 weeks of age if possible, then 2-weekly unit discharge. Children were reassessed after discharge at ages ranging from 1 to 10 years. RESULTS: Survival rates to hospital discharge rose significantly over time, from 34.5% (145/420) in 1977 through 1984, to 53.7% (312/581) in 1985 through 1992 (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7 to 2.8). Of the 434 surviving ELBW infants seen by the ophthalmologist, ROP was detected in 48.2% (68/141) in 1977 through 1984, which dropped significantly to 35.8% (105/293) in 1985 through 1992 (OR 0.6, 95% CI 0.4 to 0.9). Severe ROP (bilateral stages 3 to 5) was detected in 25.5% (36/141) in 1977 through 1984, and 17.7% (52/293) in 1985 through 1992, but the reduction was not quite statistically significant (OR 0.6, 95% CI 0.4 to 1.0). Bilateral blindness (visual acuity in each eye less than 6/60) caused by ROP occurred in only 4 (0.88%) survivors overall, 2 in each era. CONCLUSION: The increase in the survival rate of ELBW infants is not always accompanied by an increase in the rate of severe ROP or blindness, at least for ELBW infants born in some large level-3 centers.

Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome?

A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum.

Evidence that Rieger syndrome maps to 4q25 or 4q27.

We report a baby with the features of Rieger syndrome and a de novo interstitial deletion of 4q which includes band 4q26 and an adjoining GTL light band, either q25 or q27. Rieger syndrome is provisionally mapped to 4q23----q27 but band 4q26 has been excluded as a possible site, suggesting that Rieger syndrome must map to a band, either 4q25 or 4q27, adjoining 4q26.

Congenital rubella infection from reinfection of previously immunised mothers.

Two children developed congenital rubella infection when their mothers had been proven to be satisfactorily immunised against rubella before the affected pregnancy. One child was severely affected with heart lesions, brain damage, severe deafness, physical retardation, cataracts and rubella retinopathy. The other child had moderately severe sensorineural deafness and a mild reduction in visual acuity due to rubella retinopathy.

Clinical variability in a family with X-linked retinal dystrophy and the locus at the RP3 site.

One large Australian family with X-linked retinal dystrophy was found to have extreme clinical variability in the hemizygotes. One member had the typical rod-cone disease, three had the cone-rod pattern and one had macroscopic changes in the macular area only, but with low potentials in the ERG. The locus for the disease was found to be distal to L1.28 at Xp21, the site for RP3. From a study of case histories reported it seems that clinical variability can be a common feature of X-linked retinitis pigmentosa (XLRP) with the locus at Xp11.3 (RP2) or at Xp21 (RP3), and this family may well be categorized as XLRP.

Changing two-year outcome of infants weighing 500 to 999 grams at birth: a hospital study.

Survival and neurodevelopmental outcome to 2 years were determined for two cohorts of infants weighing 500 to 999 gm at birth, born in a tertiary maternity hospital. Live births increased over time from an annual average of 48.7 in the first era (January 1977 to March 1982) to 64.6 in the second era (January 1985 to December 1987), largely from referrals of additional mothers with pregnancy complications. In the first era, 33.6% (86/256) of infants survived to 2 years; the survival rate improved significantly to 45.9% (89/194) in era 2. After adjustment for birth weight, the odds ratio for survival in era 2 versus era 1 was 1.39 (95% confidence interval = 1.12, 1.73; p less than 0.01). One known survivor in each era was not seen at 2 years of age. In the first era, 59.3% (51/86) of 2-year-old children were free of disability compared with 68.5% (61/89) in era 2 (NS), but the Mental Development Index of the Bayley Scales improved significantly, from 90.0 in era 1 to 98.0 in era 2. For infants weighing less than 800 gm at birth, not only did the 2-year survival rate improve, adjusted for birth weight (odds ratio = 1.53; 95% confidence interval = 1.06, 2.20; p less than 0.05), but there was also a significant reduction in neurologic disabilities in survivors (p = 0.03). For infants weighing 800 to 999 gm at birth, there was a significant improvement in the survival rate, adjusted for birth weight (odds ratio = 1.37; 95% confidence interval = 1.04, 1.79; p less than 0.05), but the rate of neurologic disabilities was unchanged. Increased survival in our tertiary maternity center was achieved without increasing the annual number of severely disabled 2-year-old survivors.

Chemotherapy in retinoblastoma management.

Chemotherapy, in addition to surgery, irradiation, cryothermy and light coagulation has been used in three groups of patients with retinoblastoma. In the first group it was used to try to prevent the development of metastases in cases with large tumours (Reese-Ellsworth Grade 4-5), in the second group to treat local extra-ocular spread and in the third group to treat bony metastases. In the first group there were 14 children with unilateral and eight with bilateral disease (grade 4 or 5 in one or both eyes), who were given prophylactic chemotherapy; there were no significant complications. One child died from congenital heart disease five years after treatment with no signs of metastatic disease. The mean survival of the other 21 children is now 6.0 years (range 2.5-11 years). Six children with local extra-ocular spread, one with CNS involvement as well, had chemotherapy with only minor complications. One child who did not complete the chemotherapy or radiotherapy coursed died from CNS disease but the remaining five have survived for four to 13 years. Three children with bone metastases were treated with high dosage chemotherapy after marrow harvesting and then reinfusion of marrow; in two children this did not eliminate the tumour and they died but one child has now survived free from disease for six years. In our cases we have had encouraging results from the use of chemotherapy with few complications but other authors have suggested that there is a possibility of new primary tumours being caused by this treatment.

Retinopathy of prematurity in infants of 24-30 weeks' gestational age.

Over the 10-year period from January 1, 1977 to December 31, 1986, 1114 infants with gestational ages of 24 to 30 completed weeks were cared for on a long-term basis in our nursery; 757 (68%) infants survived. As expected, both the mortality rate and the prevalence of stage-3 or stage-4 retinopathy of prematurity among survivors fell with increasing maturity at birth (P less than 0.0001). Adjusting for gestational age, and excluding infants with lethal malformations, the mortality rate decreased significantly (P = 0.018) over time by an estimated 11.5%; also the survival rate of infants with at least stage-3 retinopathy of prematurity increased significantly (P = 0.005) by an estimated 6.8%. In other words, for every 10 additional survivors over the decade, six survivors would have been expected to show at least stage-3 retinopathy of prematurity in either eye. Although the prevalence of advanced stages of retinopathy of prematurity increased in immature survivors, it was not in epidemic proportions; however, it was more likely to be related to the survival of the increasing numbers of at-risk immature infants who, in earlier times, would have died.

Absence of a lateral rectus muscle associated with duplication of the chromosome segment 7q32----q34.

Absence of the right lateral rectus muscle and hypoplasia of the left was found in a child with congenital esotropia. He had mental and physical retardation, bilateral optic nerve hypoplasia, and many minor dysmorphic features, including brachycephaly, high forehead, poorly folded, low set ears, epicanthic folds, exaggerated Cupid's bow, long philtrum, and single palmar creases. Unusual features were a markedly ridged palate and a plantar crease which passed from the first and second interspace across the lateral border of the foot. He was found to have an unbalanced karyotype with duplication of chromosome segment 7q32----q34 (46,XY,der(2),inv?ins(2;7) (q21;q32q34)mat). The mother, maternal aunt, and sister of the proband all had a balanced rearrangement and were phenotypically normal.

Concurrent de novo interstitial deletion of band 2p22 and reciprocal translocation (3;7)(p21;q22).

A child is described with a de novo interstitial deletion of band 2p22 and a reciprocal translocation (3;7)(p21;q22). The child has mild developmental delay, coloboma of the right eye, and Hirschsprung's disease. The clinical and cytogenetic findings are described.

Extremely-low-birthweight infants: neurological, psychological, growth and health status beyond five years of age.

Of 60 consecutive survivors of birth weight 500-999 g, who were born in one tertiary perinatal centre from 1977 to 1980, 59 infants were assessed by a multidisciplinary team at two years of age (corrected for prematurity) and 58 children were evaluated when aged at least five years. At the latter examination, 9% of the 58 children who were assessed were severely disabled; 17% had a mild or moderate disability; and 74% had no important disability. For the 53 children who were tested, the means for the three scales of the Wechsler Preschool and Primary Scales of Intelligence were just above the test mean. The psychologist noted behavioural problems during her assessment in 50% of children, and 29% of mothers reported behavioural problems which could interfere with schooling. At the age of five years and over, five (9%) children had cerebral palsy and one child was deaf. Twenty-two (38%) children had a visual impairment, although only one child was blind; the detection of retinopathy of prematurity in the nursery was an important risk factor. Health problems with readmissions to hospital and suboptimal growth were present in many children at two years of age and frequently these problems persisted to five years of age. Although only four (7%) children were too disabled to attend a normal school, apprehension exists that many of the other children may later encounter educational difficulties. At the two-years' assessment, ascertainment of cerebral palsy had not been complete or entirely accurate and the Mental Developmental Index of the Bayley Scale tended to underestimate the later psychological performance.