First report of SYNE1 arthrogryposis multiplex congenita from Saudi Arabia with a novel mutation: a case report.

BACKGROUND: Myogenic Arthrogryposis Multiplex Congenita type 3 (AMC-3), is a rare congenital condition characterized by severe hypotonia, club feet, and multiple joint contractures often affecting both arms and legs which start prior to birth. CASE PRESENTATION: We report a full-term neonate born to first-degree cousins from fourth-generation consanguineous families, who had with antenatal history of reduced fetal movements. At birth, he was noticed to have bilateral club feet, arthrogryposis, severe hypotonia, and absent deep tendon reflexes. The patient developed difficulty in breathing probably attributed to his generalized severe hypotonia, necessitating mechanical ventilation. His creatinine-phospho-kinase, electromyogram, and brain magnetic resonance imaging were normal. Whole-exome sequencing (WES) was requested for the genetic diagnosis of the case. WES identified a novel homozygous variant c.23415-3799C > G p. in the synaptic nuclear envelope protein1 [SYNE1] gene. Seven out of 20 bioinformatic in silico programs predicted a pathogenic effect for this variant. Segregation analysis of the variant in the parents and siblings revealed that both parents and one sibling were heterozygous for the same mutation which proved the variant significance and its autosomal recessive pattern of inheritance. CONCLUSIONS: AMC3 should be suspected in patients with decreased fetal movements, severe hypotonia, absent deep tendon reflexes, and arthrogryposis. SYNE1 gene mutations can be the underlying genetic defect and molecular genetic testing can prove the diagnosis.

Facial Asymmetry in a Newly Born Baby: Diagnostic Challenge!

Introduction: Facial asymmetry during crying in neonates is an important entity which might be due to an underlying true paralysis of the facial nerve or due to the benign overlooked diagnosis of congenital absence of the depressor angularis oris muscle (DAOM). Case Report: We report a full-term newborn delivered by normal spontaneous vertex delivery with uneventful pregnancy and Apgar score of 9 and 10 at 1 and 5 minutes respectively. His parents are first-degree cousins with 4 living normal siblings. His birth weight was appropriate for his gestational age. His initial neonatal assessment was normal apart from facial asymmetry during crying in the form of deviation of the angle of the mouth to the left with an otherwise normal facial appearance. The facial asymmetry disappears at rest (without crying). This condition usually poses a diagnostic dilemma. Developmental and traumatic facial paralysis and being part of some syndromes like Mobius and CHARGE syndromes are among the most important differential diagnosis but the disappearance of the facial asymmetry at rest is diagnostic of absent DAOM which is a relatively common but missed diagnosis. Conclusions: Pediatricians should be aware about the diagnosis of DAOM in neonates with asymmetric crying face if the face was completely normal at rest with deviation of the angle of the mouth on crying which disappears on rest.

Novel homozygous mutation of PNLIP gene in congenital pancreatic lipase deficiency: an extended family study.

Introduction: Congenital pancreatic lipase deficiency (MIM 614338) is a rare genetic disorder caused by homozygous mutation in the PNLIP gene. Few cases have been reported worldwide and among them, few cases were genetically confirmed. Patients and methods: A 3-year-old girl presented with abundant greasy diarrhea started at the age of 2 years. Work up of steatorrhea including molecular testing of PNLIP gene in the patient and her family was done. Results: A novel homozygous variant c.1257G > A (p. Trp419Ter) of the PNLIP gene was detected in the patient. Her parents and two siblings were carriers for the same mutation. Pancreatic enzyme therapy was introduced, and a multidisciplinary team was involved with the education for the need for the lifelong use of pancreatic enzymes, and genetic counseling was carried out. There was a great improvement of steatorrhea with pancreatic enzymes treatment. Conclusions: PNLIP deficiency should be suspected in patients with steatorrhea who have low pancreatic lipase and an otherwise normal health and appropriate growth.