Muenke syndrome is an autosomal dominant genetic disorder that is typically characterized by unilateral or bilateral coronal synostosis, macrocephaly, midface hypoplasia, and developmental delays. This article reports a case of Muenke syndrome with a soft cleft palate. A heterozygous missense mutation c.749C>G (p.P250A) was identified in the FGFR3 gene through genetic testing. The patient exhibited typical features including coronal synostosis, bilateral hearing loss, right accessory auricle, and developmental delays and underwent surgery to repair the soft cleft palate. Cases of Muenke syndrome with cleft palate in the literature are relatively rare, and common associated symptoms include coronal suture craniosynostosis and hearing impairment. This article reports a differential diagnosis with other craniosynostosis syndromes and provides a reference for clinical diagnosis and treatment.
Humans ; Cleft Palate/surgery* ; Craniosynostoses/diagnosis* ; Mutation, Missense ; Palate, Soft/abnormalities* ; Receptor, Fibroblast Growth Factor, Type 3/genetics*

OBJECTIVE: To block the transmission of Cranio-facial-nasal syndrome (CFNS) caused by a large deletion of the EFNB1 gene through preimplantation genetic testing for monogenic disorders (PGT-M). METHODS: A patient with craniofacial deformities and his parents who had visited Shiyan People's Hospital in June 2020 were selected as the study subjects. The child underwent whole exome sequencing (WES) and qPCR validation. After genetic counseling, PGT-M was chosen for the reproductive blockage. This study was approved by the Ethics Committee of the Hospital (Ethics No.: sysrmyy-087). RESULTS: The child was diagnosed with CFNS due to a heterozygous deletion of exons 1-5 of the EFNB1 gene through WES and qPCR, which showed a X-linked dominant inheritance. The mother underwent ovarian stimulation with a modified PPOS protocol, which has yielded 11 oocytes. After ICSI fertilization, 4 blastocysts were formed, and MALBAC whole genome amplification was performed on the trophoblast biopsy cells, and SNP haplotypes of the family members and embryos were analyzed to indirectly determine the presence of maternal pathogenic haplotypes. Chromosomal copy number variation analysis was conducted through next-generation sequencing to screen for euploid embryos, resulting in the identification of two euploid embryos that did not carry the mutation of the EFNB1 gene. The first transfer was unsuccessful, but after adjusting the transfer timing through endometrial receptivity assessment (ERA), clinical pregnancy was achieved. Prenatal diagnosis at 19 weeks excluded the EFNB1 gene exons 1-5 deletion in the fetus. A healthy girl was delivered by Cesarean section at 38⁺⁶ weeks, and Q-PCR confirmed she has no aforementioned EFNB1 gene deletion. CONCLUSION This study has successfully blocked the transmission of CFNS caused by a large deletion of the EFNB1 gene (exons 1-5) using a PGT-M strategy, which may provide reference for the intervention of similar genomic variations that cannot be directly detected.
Humans ; Female ; Male ; Craniofacial Abnormalities/diagnosis* ; Ephrin-B1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Pedigree ; Asian People/genetics* ; Craniosynostoses/genetics* ; Pregnancy ; Gene Deletion ; Sequence Deletion ; Genetic Testing/methods* ; Adult ; East Asian People

Craniofacial abnormalities are common. It is important to examine the fetal face and skull Epub ahead of print during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal skull and face can increase the detection rate. When an abnormality is found, it is important to perform a detailed scan to determine its severity and search for additional abnormalities. The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some syndromes is feasible if the family history is suggestive.
Brain ; Chromosome Aberrations ; Cleft Palate ; Cranial Sutures ; Craniofacial Abnormalities* ; Craniosynostoses ; Female ; Fetus ; Humans ; Magnetic Resonance Imaging ; Micrognathism ; Palate ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; Skull ; Ultrasonography ; Ultrasonography, Prenatal*

Deformational plagiocephaly (DP) (also referred to as positional plagiocephaly) has long posed challenges for plastic surgeons because it is difficult to differentiate from several other diseases, such as unilateral coronal synostosis, hemifacial microsomia, and unilateral lambdoidal craniosynostosis. These diseases can actually masquerade as DP or vice versa. Only in recent years has the differential diagnosis among these diseases become possible through improved imaging modalities, such as computed tomography, and a greater understanding of their pathophysiology. Herein, we report a rather rare, yet severe, form of DP that can easily be confused with the aforementioned diseases.
Blepharoplasty ; Craniosynostoses ; Diagnosis, Differential ; Facial Asymmetry* ; Goldenhar Syndrome ; Humans ; Plagiocephaly ; Plagiocephaly, Nonsynostotic* ; Plastics ; Surgeons

Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.
Acrocephalosyndactylia ; Antley-Bixler Syndrome Phenotype ; Cranial Sutures ; Craniofacial Dysostosis ; Craniosynostoses* ; Diagnosis ; Genetic Counseling ; Humans ; Skull ; Sutures ; Synostosis ; Wills

The purpose of this article is to review imaging findings and to discuss the optimal imaging methods for craniosynostosis. The discussion of imaging findings are focused on ultrasonography, plain radiography, magnetic resonance imaging and computed tomography with 3-dimensional reconstruction. We suggest a strategy for imaging work-up for the diagnosis, treatment planning and follow-up to minimize or avoid ionized radiation exposure to children by reviewing the current literature.
Child ; Cranial Sutures ; Craniosynostoses* ; Diagnosis* ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Radiography ; Skull ; Ultrasonography

Most craniosynostoses are sporadic, but may have an underlying genetic basis. Secondary and syndromic craniosynostosis accompanies various systemic diseases or associated anomalies. Early detection of an associated disease may facilitate the interdisciplinary management of patients and improve outcomes. For that reason, systematic evaluation of craniosynostosis is mandatory. The authors reviewed systematic evaluation of craniosynostosis with an emphasis on genetic analysis.
Craniosynostoses* ; Diagnosis ; Humans

OBJECTIVETo investigate the diagnosis and treatment of hypotelorism.

METHODSFrom Jan. 2000 to Jan. 2014, 6 cases with hypotelorism were retrospectively studied. Among them, 3 cases had craniosynostosis, 2 had holoprosencephaly, and 1 had cleft lip. All the cases were diagnosed and treated by bone graft or spring distraction to correct the hypotelorism.

RESULTS2 cases were treated by none graft and 4 cases were treated by external spring distraction. All the patients completed the treatment successfully with obvious improvement in appearance. No complication happened. 4 cases were followed up for 2 years with an average fronto-orbital axis angle as (50 ± 8) °.

CONCLUSIONSHypotelorism can be successfully corrected by bone graft as fronto-orbital bridge or spring distraction.

Bone Transplantation ; Cleft Lip ; Craniofacial Dysostosis ; diagnosis ; surgery ; Craniosynostoses ; complications ; Humans ; Osteogenesis, Distraction ; Retrospective Studies ; Treatment Outcome

Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital disorder caused by mutations in the SALL1 gene. Its signs and symptoms overlap with other genetic syndromes, including VACTERL association, Pendred syndrome, Baller-Gerold syndrome, and cat eye syndrome. Structural vertebral abnormalities, hypoplasia of the thumb, and radial bone abnormalities, which are not usually associated with TBS, help in the differential diagnosis of these syndromes. We report the case of a family whose members were diagnosed with TBS with congenital hypothyroidism and had a novel SALL1 gene mutation.
Abnormalities, Multiple ; Anal Canal ; Aneuploidy ; Animals ; Anus, Imperforate ; Cats ; Chromosome Disorders ; Chromosomes, Human, Pair 22 ; Congenital Hypothyroidism ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Craniosynostoses ; Diagnosis, Differential ; Esophagus ; Eye ; Goiter, Nodular ; Hearing Loss, Sensorineural ; Heart Defects, Congenital ; Humans ; Kidney ; Limb Deformities, Congenital ; Radius ; Spine ; Thumb ; Trachea

Here we report the first case of a Korean infant with a cloverleaf-shaped craniosynostosis, in which the diagnosis of Beare-Stevenson syndrome was suspected upon observation of the typical morphological features. This infant exhibited craniofacial anomalies, ocular proptosis, cutis gyrata, acanthosis nigricans, prominent umbilical stump, furrowed palms and soles, hypospadia, and sacral skin tag coupled with dermal sinus tract. Brain magnetic resonance imaging revealed that the patient also had non-communicating hydrocephalus with Chiari malformation. This is the 8th report of Beare-Stevenson syndrome in the literature, which was confirmed by the detection of a Tyr375Cys mutation in the fibroblast growth factor receptor 2 (FGFR2) gene.
Syndrome ; Receptor, Fibroblast Growth Factor, Type 2/*genetics ; Polymorphism, Single Nucleotide/genetics ; Mutation ; Male ; Korea ; Infant, Newborn ; Humans ; Genetic Predisposition to Disease/genetics ; DNA Mutational Analysis ; Craniosynostoses/diagnosis/*genetics ; Craniofacial Abnormalities/diagnosis/genetics ; Abnormalities, Multiple/diagnosis/*genetics