Paula and Bobby
Parents of Lillie
Hartsfield syndrome (HRTFDS)
What is Hartsfield syndrome (HRTFDS)?
This rare disease is a genetic syndrome with two major, serious symptoms.
The first is holoprosencephaly, which is when the brain does not develop properly. The second is ectrodactyly, which affects the hands and feet.
There have been less than 20 cases reported of this rare syndrome to date, and most of these cases have been in males.
This syndrome is also known as:
Hartsfield (1984) - holoprosencephaly; ectrodactyly; cleft face Holoprosencephaly, Ectrodactyly, And Bilateral Cleft Lip/palate
What gene changes cause Hartsfield syndrome (HRTFDS)?
Mutations in the FGFR1 gene are responsible for causing the syndrome. It has been found that the syndrome can be inherited generally in an autosomal dominant pattern. However there have been a few cases where it has been inherited in an autosomal recessive pattern.
In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms, but have a 25% chance of passing the copies of the gene mutations onto each of their children.
What are the main symptoms of Hartsfield syndrome (HRTFDS)?
One of the main and most serious symptoms of the syndrome is holoprosencephaly. This affects the development of the brain. It occurs when the two hemispheres of the brain don’t divide properly. In the most severe cases the brain fails to divide at all, which in most cases will cause premature death. In less severe cases, the two hemispheres of the brain partially divide which in turn can lead to a number of related medical issues. These include a malfunctioning pituitary and diabetes insipidus.
The second main symptom is ectrodactyly, which is a deep slip through the hands and or feet. This then usually results in missing fingers and toes.
A cleft lip/palate completes the triad of the syndrome.
Seizures and developmental delay are also known symptoms of the syndrome.
Possible clinical traits/features:
Wide nose, Abnormality of the sense of smell, Cleft palate, Aplasia/Hypoplasia of the corpus callosum, Aplasia/Hypoplasia affecting the eye, Aplasia/Hypoplasia of the radius, Absent nares, Telecanthus, Ptosis, Microcephaly, Respiratory failure, Holoprosencephaly, Gonadotropin deficiency, Global developmental delay, Hypertelorism, Hypernatremia, Hypotelorism, Hypospadias, Hypoplasia of the frontal bone, Posteriorly rotated ears, Non-midline cleft lip, Syndactyly, Autosomal dominant inheritance, Cryptorchidism, Craniosynostosis, Agenesis of corpus callosum, Split hand, Ectrodactyly, Downslanted palpebral fissures, Depressed nasal bridge, Epicanthus, Encephalocele, Cleft upper lip, Diabetes insipidus, Neonatal hypotonia, Micropenis, Intrauterine growth retardation, Low-set ears, Low-set, posteriorly rotated ears, Lobar holoprosencephaly
How does someone get tested for Hartsfield syndrome (HRTFDS)?
The initial testing for Hartsfield syndrome (HRTFDS) can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Hartsfield syndrome (HRTFDS)
In the original report by Hartsfield et al., (1984) the male infant, who died at 7 days, was said to have a right-sided cleft lip and palate. Drawings of the face suggest that the cleft might have been more extensive, and it should be noted that at post-mortem holoprosencephaly was found - the facial cleft does look like a premaxillary agenesis. The other important finding was the presence of ectrodactyly, variably involving all four limbs. Some digits were missing in the appropriate ray, and in one arm the radius was absent. There were also abnormalities of the sutures. The other unusual feature, in view of the holoprosencephaly, was the hypertelorism, whereas hypotelorism might have been expected.
Young et al., (1992) reported a very similar case. A further male child with features of the condition was reported by Imaizumi et al., (1998). Corona-Rivera et al., (2000) reported a male with features of the condition who had an apparently balanced de novo translocation-T(2;4)(q14.2;q35). Abdel Meguid and Ashour (2001) reported a 1-year-old child with features of the condition. There was no cleft lip or palate. Konig et al., (2003) reported a male case with features of the condition. The patient reported by Zechi-Ceide et al., (2009) had a semilobar holoprosencephaly, ectrodactyly bilateral clefting and severe retardation. The basal ganglia were partially fused and the brain stem was hypoplastic.
Five patients were reported by Vilain et al., (2009). Vermian hypoplasia was common. Hypogonadotrophic hypogonadism and diabetes insipidus were features in some. The literature is well reviewed. It is difficult to place thge brief report by Thapa et al., (2010). The child had ectrodactyly, cleft lip/palate and had cerebellar vermus atrophy with a large cisterna magna
A microduplication at Xq24 was descibed in a patient by Takenouchi et al., (2012). Life-threating hpernatremia was part of the clinical picture. SLC25A43, SLC25A5, CXorf56 and UBE2A were included in the duplication. Heterozgous or homozygous mutations in FGFR1 have been found to cause this syndrome (Somonis et al., 2013). Dhamija et al., (2014) presented 2 affected sibs with heterozygous mutations, presumably from a mosaic parent.
* This information is courtesy of the L M D.
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