Antenatally detected holoprosencephaly-polydactyly (pseudotrisomy 13) syndrome

No abstract available
Sri Lanka Journal of Child Health, 2023: 52(2): 219-222


Introduction
Pseudotrisomy 13 syndrome was first suggested in 1989 by Hewitt BG, et al 1 . It was identified in patients with holoprosencephaly and clinical features suggestive of trisomy 13, such as microcephaly, hypotelorism, cleft palate, and anophthalmia in the presence of a normal kayotype 2,3 . Holoprosencephaly and polydactyly are the hallmarks in this anomaly 4 . We present a patient with phenotypic features of trisomy 13 with a normal karyotype.

Case report
A baby girl, weighing 2300g (-2SD to -3SD), was delivered at term by normal vaginal delivery to healthy non-consanguineous elderly parents (37year-old mother and 43-year-old father) with two healthy children. This was the third pregnancy and there was no previous history of miscarriages or early neonatal deaths. Mother has taken preconceptional folic acid and the pregnancy was not complicated with any medical illness. The antenatal ultrasound scan (USS) done at 26 weeks of gestation revealed holoprosencephaly, ventricular septal defect (VSD) and midline facial cleft, suggestive of Patau syndrome (Trisomy 13) as shown in Table 1 The baby was born with Apgar scores of 8, 9 and 10 at 1, 5 and 10 minutes of age respectively. She was noted to have microcephaly (occipito-frontal circumference 28cm, <5 th centile), short birth length (length 44cm, on -3SD), hypertelorism, bilateral cleft lip with midline cleft palate, postaxial polydactyly, long systolic murmur in left sternal edge suggestive of VSD, and epicanthic folds ( Figure 1).
A clinical diagnosis of Trisomy 13 was made and karyotyping was arranged.
USS of the brain confirmed features of semi-lobar holoprosencephaly without hydrocephalus ( Figure  2).
USS of the abdomen revealed a right sided cystic kidney ( Figure 3).
2D echocardiogram revealed tetralogy of Fallot with pulmonary atresia and duct dependent pulmonary circulation. Spinal x-rays did not reveal any structural anomalies.
The baby was given multidisciplinary care with orthodontist, in view of repairing facial and palatal clefts, plastic surgeon, for removal of additional finger, nephrologist, for possible chronic kidney disease in future, and speech therapist for assessment of swallowing. She was fed with expressed breast milk via nasogastric tube and was discharged on day 12 of life after parental counselling for Trisomy 13, the diagnosis at that moment of time.
Parents were informed in detail about multisystem involvement with possible future complications, short life span and genetic counselling arranged considering the recurrence in future pregnancies. The baby passed away on day 32 of life, possibly due to the closure of the patent ductus arteriosus. It was only later that her karyotype was reported as normal which led us to consider Pseudotrisomy 13 ( Figure 4).

Discussion
Pseudotrisomy 13 is considered to have an autosomal recessive inheritance due to its occurrence in multiple children of normal parents and children born to consanguineous parents 2 . However, a few sporadic cases have also been reported 2 . Genes responsible for the disorder have not been confirmed yet. Some studies have indicated the gene FBXW11 of the long arm of chromosome 5 as responsible 5 . Recent evidence suggests it is not monogenic 6 .
The Meckel syndrome, Pallister-Hall syndrome, trisomy 13, Hydrolethalus syndrome and Smith-Lemli-Opitz syndrome must be excluded using characteristic findings. Hydrolethalus syndrome is characterized by the absence of midline cerebral structures, hydramnios, external hydrocephalus, preaxial polydactyly of the feet, postaxial polydactyly of the hands, congenital heart defects, and micrognathia 4,8 . Our patient did not have polyhydramnios, pre-axial polydactyly of the feet and hydrocephalus to suggest Hydrolethalus syndrome. Meckel syndrome occurs with polycystic kidneys, occipital encephalocele and polydactyly, and Pallister-Hall syndrome may be associated with post-axial polydactyly, syndactyly, hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and, occasionally, with holoprosencephaly 4,8 . Smith-Lemli-Opitz syndrome has characteristic facial features including anteverted nostrils, ptosis of eye lids, syndactyly of second and third toes, polydactyly and microcephaly. Our patient did not have occipital encephalocele to suggest Meckel syndrome and hypothalamic hamartoblastoma, syndactyly and evidence of pituitary insufficiency to suggest Pallister-Hall syndrome and facial features were not in favor of Smith-Lemli-Opitz syndrome.
Antenatal diagnosis of Pseudotrisomy 13 is possible with the use of ultrasound imaging and karyotyping of samples from amniocentesis. Antenatal diagnosis is very important for genetic counselling and prognostication.