IllnessHartsfield syndrome, differential diagnosis

NGS +

Hartsfield syndrome is a rare disorder characterized by holoprosencephaly and ectrodactyly of the hands and/or feet. In most severe forms of holoprosencephaly, the brain does not divide at all, so cyclopia and proboscis develop above the eye. Most babies with severe symptomatology die before or shortly after birth. In less severe cases, the brain is divided partially. The life expectancy of affected individuals depends on the severity of symptoms. Patients often have other brain abnormalities such as pituitary dysfunction. Dysfunction in other parts of the brain can lead to seizures and problems regulating body temperature and sleep patterns. These patients have mild to severe developmental delay. Another characteristic symptom is ectrodactyly, which affects the hands and feet on one or both sides. Other features include craniosynostosis, heart defects, abnormalities of the spine and genitalia. Some affected individuals have prominent facial features with hyper- or hypotelorism, small or unusually shaped ears and cleft lip with or without cleft palate. Hartsfield syndrome is usually caused by mutations in the FGFR1 gene and can be inherited either autosomal dominantly or, rarely, autosomal recessively. The molecular genetic diagnostic yield is not complete and, based on 35 positive cases, it is unknown. A negative DNA test result may not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK349073/

• Alias: FGFR1-related Hartsfield syndrome
• Alias: Hartsfield-Bixler-Demyer syndrome
• Alias: Holoprosencephaly split hand/foot syndrome
• Alias: Holoprosencephaly, ectrodactyly + bilateral cleft lip/palate
• Alias: Holoprosencephaly, hypertelorism + ectrodactyly syndrome
• Alias: Holoprosenzephalie-Ektrodaktylie-Lippen-Kiefer-Gaumenspalte-Syndrom
• Allelic: ADULT [Acro-Dermato-Ungual-Lacrimal-Tooth] syndrome (TP63)
• Allelic: Hay-Wells syndrome [Ankyloblepharon-ectodermal defects-cleft lip/palate] (TP63)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Limb-mammary syndrome (TP63)
• Allelic: Microphthalmia with coloboma 5 (SHH)
• Allelic: Mullegama-Klein-Martinez syndrome (STAG2)
• Allelic: Osteoglophonic dysplasia (FGFR1)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Rapp-Hodgkin syndrome [anhidrotic ectodermal dysplasia, cleft lip/palate] (TP63)
• Allelic: Schizencephaly (SHH, SIX3)
• Allelic: Split-hand/foot malformation 4 (TP63)
• Allelic: Trigonocephaly 1 (FGFR1)
• Cornelia de Lange syndrome 2 (SMC1A)
• Cornelia de Lange syndrome 4 (RAD21)
• Culler-Jones syndrome (GLI2)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (TP63)
• Genitourinary and/or/brain malformation syndrome (PPP1R12A)
• Hartsfield syndrome (FGFR1)
• Holoprosencephaly 10 (DISP1)
• Holoprosencephaly 11 (CDON)
• Holoprosencephaly 12, with/-out pancreatic agenesis (CNOT1)
• Holoprosencephaly 13, XL (STAG2)
• Holoprosencephaly 2 (SIX3)
• Holoprosencephaly 3 (SHH)
• Holoprosencephaly 4 (TGIF1)
• Holoprosencephaly 5 (ZIC2)
• Holoprosencephaly 9 (GLI2)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Kabuki syndrome 1 (KMT2D)
• Microcephaly 7, primary, AR (STIL)
• Mungan syndrome (RAD21)
• Neurodevelopmental disorder with nonspecific brain abnormalities with/-out seizures (DLL1)
• Orofacial cleft 8 (TP63)
• Single median maxillary central incisor (SHH)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Stromme syndrome (CENPF)
• Vissers-Bodmer syndrome (CNOT1)