Young–Madders syndrome
| Young–Madders syndrome | |
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| Gross pathology specimen from a case of alobar holoprosencephaly, a clinical manifestation of Young–Madders syndrome first described as a new condition by doctors Young and Madders in 1987. |
Young–Madders syndrome, alternatively known as Pseudotrisomy 13 syndrome or holoprosencephaly–polydactyly syndrome, is a
Though it is now thought that earlier cases were misdiagnosed as other genetic disorders with similar
Presentation
Young–Madders syndrome is detectable from the fetal stage of development largely due to the distinctive consequences of holoprosencephaly, a spectrum of defects or malformations of the brain and face. Facial defects which may manifest in the eyes, nose, and upper lip, featuring cyclopia, anosmia, or in the growth of only a single central incisor, and severe overlapping of the bones of the skull.[2][3] Cardiac and in some cases pulmonary deformities are present.[2] Another signature deformity is bilateral polydactyly, and many patients also suffer from hypoplasia and genital deformities.[1]
Diagnosis
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Management
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History
Early cases
A publication in the
Identifying chromosome thirteen
Sporadic reports of the case continued, with 'pseudotrisomy 13' becoming a common term due to the similar pathology to Trisomy 13. However, there was a growing belief that unlike Trisomy 13, Young–Madders syndrome was not caused by a duplicated chromosome, and in fact the cause lay in some other fault with chromosome thirteen. In 1991 a publication in the Journal of Medical Genetics by a group of eight doctors, based on a five-patient case-study, argued that Trisomy 13 and Young–Madders syndrome were two distinct conditions and renamed the disorder to avoid confusion. Their case studies, when viewed together, suggested a recessive genetic cause,[4]
based on the repeated instances of holoprosencephaly polydactyly in the aforementioned five cases, which led to the suspicion of an anomaly in chromosome 13's genetic coding.[4] Chromosome thirteen spans about 114 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA in cells. Problems with this chromosome account for several conditions including nonsyndromic deafness, Waardenburg syndrome and Wilson's disease.[4]
The majority of the cases discussed in the journal were still born, with death occurring between twenty-six and thirty-four weeks of gestation. All suffered with the features of Young–Madders syndrome, with varying cardiac problems and facial deformities. The distinctive bilateral polydactyly and overlapping of the cranial skull plates were present, though some had no deformities in their internal organs while others had lung deformities alone. Hydrocephalus and holoprosencephaly were present in all.
Further research
After the publications by Verloes, A., S. Aymé et al. 'holoprosencephaly-polydactyly syndrome' became the preferred term. Doctors Hennekam and Van Noort published later in 1991 an account of further case studies involving a brother and sister which emphasised the involvement of genetic heart defects. They also noted that the parents were second-cousins.[5] A pair of siblings with holoprosencephaly and hypoplasia were recognised in 1993, with one of the siblings having polydactyly.[6] By 1994 a sufferer had been identified with a median cleft lip, cardiac and genital deformities which matched those found by Young and Madders. A review of twenty-two reported cases took place, finding 20 instances of polydactyly. Blood tests and karyotype were normal, further evidencing a distinction between the condition and that of Trisomy 13.[7] In 2000 another case was published were the parents were first cousins, thus providing more evidence that the condition was autosomal recessive.[8] In 2006 a report in the Journal of Human Genetics on a male patient with all the symptoms of Young–Madders syndrome - including severe facial deformities and mild intellectual disability - built upon a 1993 genetic study to identify duplicate codings and other anomalies on gene FBXW11 as a possible cause of the condition.[9]