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X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome
A rare multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, growth retardation, hearing impairment, characteristic facial dysmorphology (including prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, long face, sagging cheeks, anteverted nares, and pointed chin), generalized hypotonia, joint hypermobility, gluteal crease with sacral caudal remnant and sacral dimple, and variable neurological features. Various ophthalmic, cutaneous, musculoskeletal, gastrointestinal, and cardiovascular anomalies have also been described.
ORPHA:480907Classification level: Disorder
- Synonym(s): -
- Prevalence: <1 / 1 000 000
- Inheritance: X-linked recessive
- Age of onset: Neonatal, Antenatal
- ICD-10: Q87.0
- OMIM: 300966
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Due to the small number of known affected individuals, the prevalence of this condition remains unknown. Globally, some 30 cases are known.
The main clinical features include growth retardation, delayed speech and language development, delayed gross motor development, generalized hypotonia, intellectual disability and symptoms of autism spectrum disorder. Microcephaly, facial dysmorphism, hearing impairment, variable brain morphological abnormalities, and congenital heart defects, hypospadias and cryptorchidism have also been reported.
The disorder is caused by pathogenic mutations in the TAF1 gene (Xq13.1). The encoded protein, transcription initiation factor TFIID subunit 1, is a part of the transcription factor II D complex that participates in the initiation of the transcription of RNA polymerase II transcription-dependent genes.
Diagnosis is based on clinical examination and genetic testing.
The main differential diagnosis options include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings.
Antenatal diagnosis is possible if a familial pathogenic variant has been identified.
The pattern of inheritance is X-linked. Where the female is a carrier, at risk couples should be informed that for each pregnancy the male offspring have a 50% risk of being affected and female offspring have a 50% risk of being a carrier. Females may rarely be affected due to skewed X chromosome inactivation.
Management and treatment
Management is symptomatic. After initial diagnosis, evaluation by a pediatric urologist, pediatric cardiologist, pediatric neurologist, otorhinolaryngologist or other relevant specialist may be warranted to rule out associated congenital abnormalities.
Studies suggest that the symptoms are generally not progressive; however, individual cases with progressive symptomatology have been reported. Longitudinal data regarding life expectancy is currently unavailable due to the small number of known cases.
A summary on this disease is available in Español (2021) Français (2021) Nederlands (2021)