Correction of Spine Deformity in Patients With Melnick-Needles Syndrome

Lykissas, Marios G.; Crawford, Alvin H.; Shufflebarger, Harry L.; Gaines, Sean; Permal, Venkat

doi:10.1097/bpo.0b013e3182776edb

Cited by 5 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The general symptoms of MNS include craniofacial disproportion, prominent supraorbital ridge, exorbitism, hypodontia, micrognathia, scoliosis, short ribbon‐like ribs, bowing of the long bones and sclerosis of the base of the skull (O'Connell et al, 2018). Partially serious MNS patients present with hydronephrosis, mitral and tricuspid valve prolapse, hypoplastic thorax and omphalocele (Lykissas et al, 2013). Studies have revealed that MNS is an X‐linked dominant inheritance that is mostly caused by a missense mutation in exon 22 of the FLNA gene (Foley et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Mutation of FLNA attenuating the migration of abdominal muscles contributed to Melnick–Needles syndrome (MNS) in a family with recurrent miscarriage

Luo

Yang

Zeng

et al. 2023

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Filamin A, encoded by the X‐linked gene FLNA, links the cell membrane with the cytoskeleton and acts as a regulator of the actin cytoskeleton. Mutations in FLNA cause a large spectrum of congenital malformations during embryonic development, including Melnick–Needles syndrome (MNS). However, reports of MNS, especially in males, are rare, and the pathogenesis molecular mechanisms are not well understood. Methods We found a family with two consecutive miscarriages of similar fetuses with multiple malformations. DNA was extracted from peripheral blood and tissues, and whole exome sequencing was performed for genetic analysis. Then, we created a C57BL/6 mouse with a point mutation by CRISPR/Cas‐mediated genome engineering. The migration of primary abdominal muscle cell was detected by wound healing assay. Results The first fetus showed congenital hygroma colli and omphalocele identified by ultrasound at 12 wks; the second fetus showed hygroma colli and thoraco abdominoschisis at 12 wks, with a new hemizygous mutation c.4420G>A in exon 26 of the FLNA gene, which is predicted to cause an amino acid substitution (p.Asp1474Asn). The mother and grandmother were both present in the c.4420G>A heterozygous state, and the mother's healthy brother had wild‐type FLNA. These FLNA‐mutated mice exhibited a broader central gap between the rectus abdominis than the wild type (WT), similar to the midline structure dysplasia of the abdominal wall in the two fetuses. Wound healing assays showed the attenuated migration capacity of abdominal muscle cells in mice with mutated FLNA. Finally, we summarized the cases of MNS with FLNA mutation from the accessible published literature thus far. Conclusion Our research revealed a mutation site of the FLNA for MNS and explored the mechanism of midline structure dysplasia in the abdominal wall of male patients, which could provide more evidence for the clinical diagnosis and genetic counseling of families with these disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Mutation of FLNA attenuating the migration of abdominal muscles contributed to Melnick–Needles syndrome (MNS) in a family with recurrent miscarriage

Luo

Yang

Zeng

et al. 2023

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Females with MNS have characteristic clinical and radiologic diagnostic findings. Table 1 shows details of the clinical features of patients with MNS reported in the past 15 years [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

A family of Melnick-Needles syndrome: a case report

Lee

Kim

et al. 2020

BMC Pediatr

View full text Add to dashboard Cite

Background: Melnick-Needles syndrome (MNS) is an extremely rare osteochondrodysplasia caused by a mutation of FLNA, the gene encoding filamin A. MNS is inherited in an X-linked dominant manner. In this study, we describe three members of the same family with MNS, who exhibited different phenotypic severity despite having an identical FLNA gene mutation. Case presentation: The patient was 16 months old, with a history of delayed physical development, multiple upper respiratory infections and otitis media episodes. She was referred to our orthopedic clinic because of bowed legs and an abnormal plain chest radiograph. Both upper and lower extremities were bowed. Plain X-rays showed thoracolumbar kyphoscoliosis, with anterior and posterior vertebral scalloping, and thin, wavy ribs. Hypoplasia of the pubis and ischium, with bilateral coxa valga, were also noted. Target exome sequencing revealed a heterozygous mutation of FLNA, c.3578 T > C, p.Lys1193Pro, which confirmed the diagnosis of MNS. Her older sister and mother had minimal deformities of the axial and extremity skeleton, but genetic analyses revealed the same FLNA mutation as the patient. The mutation identified in this family has not been previously reported. Conclusion: This report illustrates the potential inherited nature of MNS and the phenotypic variability of clinicoradiologic characteristics. In patients with traits suggestive of MNS, a careful medical and family history should be obtained, and genetic testing should be performed for the patient, as well as all family members.

show abstract