IllnessHoloprosencephaly, differential diagnosis

NGS +

Non-syndromic holoprosencephaly patients often have microcephaly or macrocephaly, the latter based on hydrocephalus. Other external features may include cleft palate (+/-cleft lip), a single maxillary central incisor and microphthalmos or anophthalmos. The severity of the facial features is somewhat related to the severity of brain malformations. Some individuals exhibit only a microform of holoprosencephaly. Most patients have delayed development and intellectual disability, often with pituitary dysfunction causing diabetes insipidus, for example. Additional brain dysfunctions may cause seizures, feeding difficulties and problems regulating body temperature, heart rate and respiration as well as hyposmia/anosmia. Non-syndromic holoprosencephaly is usually inherited in an autosomal dominant manner, often with reduced penetrance. Mutations in ~20 genes can cause non-syndromic holoprosencephaly, barely ~15% of cases are due to mutations in the SHH, ZIC2, SIX3 or TGIF1 genes. De novo mutations are also observed. In most affected families, the causative gene mutation currently eludes the DNA analyses. More complex disorders with holoprosencephaly as an occasional finding include the syndromes of Kallman-2, Hartsfield, Stromme and Smith-Lemli-Opitz. A negative molecular genetic test result does certainly not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1530/

• Alias: "Cyclopia"
• Alias: "Zyklopie"
• Alias: Holoprosencephaly sequence
• Alias: Isolated holoprosencephaly
• Alias: Signs of arhinencephaly
• Allelic: Basal cell nevus syndrome (PTCH1)
• Allelic: Basal cell nevus syndrome (SUFU)
• Allelic: Growth hormone deficiency with pituitary anomalies (HESX1)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Medulloblastoma, desmoplastic (SUFU)
• Allelic: Pituitary hormone deficiency, combined, 5 (HESX1)
• Cornelia de Lange syndrome 3 (SMC3)
• Cornelia de Lange syndrome 4 (RAD21)
• Culler-Jones syndrome (GLI2)
• 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 7 (PTCH1)
• Holoprosencephaly 9 (GLI2)
• Holoprosencephaly spectrum, severe developmental delay, brain malformations [panelapp] (PLCH1)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Joubert syndrome 32 (SUFU)
• Kabuki syndrome 1 (KMT2D)
• Microcephaly 7, primary, AR (STIL)
• Microphthalmia with coloboma 5 (SHH)
• Mullegama-Klein-Martinez syndrome (STAG2)
• Mungan syndrome (RAD21)
• Neurodevelopmental disorder with nonspecific brain abnormalities with/-out seizures (DLL1)
• Neurofacioskeletal syndrome with/-out renal agenesis (HS2ST1)
• Schizencephaly (SHH, SIX3)
• Septooptic dysplasia (HESX1)
• Single median maxillary central incisor (SHH)
• Stromme syndrome (CENPF)
• Vissers-Bodmer syndrome (CNOT1)