In the autosomal recessive form, hypotonia at birth with severe involvement of the respiratory and swallowing muscles as well as the electrophysiological evidence of a neuromuscular transmission disorder, address the diagnostic protocol towards any of the different forms of congenital myasthenia. Targeted sequencing genes for congenital myasthenia should include also LAMA5 gene screening.

In the dominant form, symptoms like mild cranio-facial dysmorphisms, delayed cranial suture closure and slowed growth, mild hypotonia, joint laxity and episodes of hypoglycemia should suggest any of the congenital connective multisystem syndromes. Targeted sequencing genes for congenital connective tissue diseases including also LAMA5 gene is advised.

Since late infancy symptoms of osteoarticular, muscular and intestinal involvement dominate the clinical picture. The red flag to suspect LAMA5 syndrome is the contemporary occurrence of joint laxity and pain, with x-ray evidence of serum negative osteoarthritis together with fatigability, myalgias, scarce tolerance to effort and hyperCKemia, as well as celiac-like malabsorption symptoms with negative celiac blood tests and type III celiac classification-like duodenal histopathology (villous atrophy, glandular crypt hyperplasia, surface enterocytes of low height, irregular brush-border and intraepithelial lymphocytes number increase). Reported or current evidence of two weeks to one-month delay in healing of surgical or accidental skin wounds, involving epidermis and dermis layers, in the proband and/or in others family members further support the diagnosis of LAMA5 syndrome.

Management and surveillance
Non-steroidal anti-inflammatory treatments together with glucosamine and chondroitin sulphate dietary supplements may help to alleviate existing joint pain and osteoarticular symptoms. Mesalazine (5-aminosalicylic acid, 5-ASA) coupled to sulfapyridine has been effective to treat LAMA5 patients with osteoarthritis complicated by intra-articular effusion. Combination with methotrexate seems not to improve therapeutic response. Muscle pain and fatigability respond to dietary supplementation with magnesium and potassium-rich products, together with riboflavin, calcifediol and L-Carnitine.

Aerobic activities such as swimming, yoga and pilates can contribute to maintaining the patient’s wellness. The practice of other sports is frequently complicated by joint sprains, muscle tears and worsening of pain and muscle fatigue with difficulty of recovering.

Gastrointestinal symptoms including abdominal pain and constipation alternating with diarrhea are usually controlled or eliminated by lactose-free diet and nutrition for coeliacs. Supplementation with ascorbic acid is generally sufficient to correct iron deficiency. Adequate hydration and intestinal lubricants are useful to control the symptoms. Rectal prolapse, haemorrhoids and rectocele respond to topical treatments but in the most severe cases surgical treatment is mandatory.

Regarding the wound healing, major complications occurred after caesarean section. In these patients surgical suture either with thread or staples were repeated two or three times at ten days interval. The association of fibrin glue with threaded suture gives a better response.

Orthodontic interventions from childhood growth until adulthood are the norm. Dental implants are indispensable in the most severe cases with dental agenesis.

Periodic ophthalmology counseling is necessary from school-age onwards.